Thiazolidinediones abrogate cervical cancer growth.

Peroxisome proliferator-activated receptor gamma (PPAR γ) is activated by thiazolidinedione drugs (TZDs) and can promote anti-cancer properties. We used three TZDs (pioglitazone, rosiglitazone, and ciglitazone) to target cervical cancer cell lines and a nude mouse animal model. Each agent increased activation of PPAR γ, as judged by a luciferase reporter gene assay in three HPV-associated cell lines (CaSki, SiHa, and HeLa cells) while decreasing cellular proliferation in a dose-dependent manner. They also promoted Oil Red O accumulation in treated cell lines and upregulated the lipid differentiation marker adipsin. Interestingly, xenograft HeLa tumors in nude mice treated with 100mg/kg/day pioglitazone exhibited decreased growth compared to control mice or mice treated with standard cervical chemotherapy. In conclusion, TZDs slow tumor cell growth in vitro and in vivo with decreases in cell proliferation and increases in PPAR γ and adipsin. These agents may be interesting treatments or treatment adjuncts for HPV-associated cancers or perhaps even precancerous conditions.

Cervicofacial Rhytidectomy After Radiotherapy for Head and Neck Tumors.

IMPORTANCE: Whether undergoing cervicofacial rhytidectomy after radiotherapy for tumors of the head and neck is associated with increased complication rates and therefore should be avoided remains unknown. OBJECTIVE: To evaluate complication rates in patients who have undergone cervicofacial rhytidectomy after radiotherapy for head and neck tumors and compare these rates with those of patients who have not undergone radiotherapy. DESIGN, SETTING, AND PARTICIPANTS: Retrospective review of the medical records of 16 patients who underwent cervicofacial rhytidectomy after completing radiotherapy for head and neck tumors and those of 16 age-matched control participants who did not undergo radiotherapy. Patients underwent treatment from July 1, 2006, through February 28, 2014, with final follow-up on February 28, 2014. Complications after surgery were reviewed and data for surgery type, technique, radiation dose and delivery method, and time to surgery after radiotherapy were analyzed. Data were collected from June 1 through December 31, 2013, and analyzed from January 1, 2014, through June 1, 2015. MAIN OUTCOMES AND MEASURES: Rate of complications after surgery. RESULTS: The radiotherapy and control group patients were a mean of 62 years old. In the radiotherapy group, 8 of 16 were women; 14 of 16 were women in the control group. Two major complications, 1 hematoma and 1 perioperative stroke, occurred in the 16 patients who composed the study cohort. In the control group, there was 1 case of transient facial nerve weakness and 1 case of cellulitis that was successfully treated with antibiotics. Two patients experienced wound dehiscence, and no incidents of motor or sensory nerve injury occurred. Subcutaneous face-lift (3 of 3 patients [100%] vs 1 of 13 patients [8%] who underwent superficial musculoaponeurotic system and deep-plane face-lifts; P = .02) and the addition of chemotherapy (4 of 9 patients [44%] vs 0 of 7 patients who did not receive chemotherapy; P = .04) were associated with increased complications. Being older and the time from completion of radiotherapy and surgery did not show any correlation to complications. CONCLUSIONS AND RELEVANCE: Aesthetic facial surgery after radiotherapy has an increased risk for complication compared with facial surgery without radiotherapy. The incidence of wound dehiscence is elevated in the population undergoing radiotherapy but can be managed conservatively in most cases. Patients who undergo radiotherapy must be counseled on the increased risk for complications before proceeding with cervicofacial rhytidectomy. LEVEL OF EVIDENCE: 3.

Parent, dentist, and orthodontist satisfaction following alveolar cleft repair using recombinant human bone morphogenic protein.

OBJECTIVE: Our aim was to evaluate dental/orthodontic outcomes for patients who underwent recombinant human bone morphogenic protein (rhBMP-2) alveolar cleft repair and to examine parental satisfaction following the procedure. Design Retrospective review. Setting Tertiary children's hospital. Participants Parents, dentists, and orthodontists completed satisfaction questionnaires. Main Outcome Measures Parent, dentist, and orthodontist satisfaction with the use of rhBMP-2 in alveolar cleft repair. Results Parent response rate was 71.4% (30/42). The dentist response rate was 60% (18/30). The orthodontist response rate was 53.3% (16/30). Parent and patient satisfaction was 93.3% and 83.3%, respectively. Of dentist respondents, 55.6% reported that the bone quality and alveolar ridge mucosal repair allowed for dental treatment. Of orthodontist respondents, 87.5% reported the graft enabled treatment, and 73.3% felt the graft prevented tooth root exposure and resorption. Conclusions Parents, dentists, and orthodontists are satisfied with outcomes when rhBMP-2 is used for alveolar cleft repair. The bone formed was reported as adequate to support dental and orthodontic treatment in most cases with few complications. Because of safety concerns over the use of this product in an off-label manner, further controlled studies are warranted.

Management of complications from alloplastic implants in rhinoplasty.

PURPOSE OF REVIEW: Alloplasts have long been used in rhinoplasty, but their use remains controversial. Many complications are associated with their implementation in rhinoplasty. This article elucidates these complications and provides recommendations for management. RECENT FINDINGS: Several recent articles have been published presenting experience and outcomes regarding alloplast use in rhinoplasty. In many of these studies, a specific section has been dedicated to outlining the complications encountered by the authors. Oftentimes, a short summary of the complications and their management is provided. By examining the data from these studies, one can conclude several things about the management of complications involving alloplastic implants in rhinoplasty: each case must be approached on an individual basis; clinical decision-making is dictated by physical exam findings and severity of the complication; removal of the implant must be strongly considered; and revision rhinoplasty after an alloplastic complication usually necessitates an autologous graft. SUMMARY: Alloplasts continue to be a controversial option in rhinoplasty. The surgeon must be cognizant of the risks and benefits of their use. A frank preoperative discussion of possible complications with the patient is important. Additionally, prompt recognition and appropriate management of complications is essential to minimize permanent sequelae.

Synthetic hydrogel scaffold is an effective vehicle for delivery of INFUSE (rhBMP2) to critical-sized calvaria bone defects in rats.

Medtronic's INFUSE Bone Graft provides surgeons with a potent tool for stimulating bone formation. Current delivery vehicles that rely on Absorbable Collagen Sponges (ACS) require excessive quantities of the active ingredient in INFUSE, recombinant human Bone Morphogenic Protein-2 (rhBMP2), to achieve physiologically relevant concentrations of the growth factor, driving up the cost of the product and increasing the likelihood of undesirable side effects in neighboring tissues. We demonstrate that a simple light-mediated, thiol-ene chemistry can be used to create an effective polymer delivery vehicle for rhBMP2, eliminating the use of xenographic materials and reducing the dose of rhBMP2 required to achieve therapeutic effects. Comprised entirely of synthetic components, this system entraps rhBMP2 within a biocompatible hydrogel scaffold that is degraded by naturally occurring remodeling enzymes, clearing the way for new tissue formation. When tested side-by-side with ACS in a critical-sized bone defect model in rats, this polymeric delivery system significantly increased bone formation over ACS controls.

Congenital nasolacrimal duct cyst/dacryocystocele: An argument for a genetic basis.

Embryogenesis of a congenital nasolacrimal duct (NLD) cyst is attributed to the failure of the Hasner membrane of the NLD system to cannulate. Prenatal diagnosis of congenital NLD cysts supports the argument for a developmental error, with a postnatal prevalence of 6%. The role of a genetic basis for this malformation has never been ascribed. We present a set of monozygotic twins with bilateral congenital NLD cysts as an argument for a genetic basis of this entity. A case report and literature review were performed. We present two cases of bilateral congenital NLD cysts occurring in a set of monozygotic twins. Patients were delivered at 37 weeks via cesarean section. The pregnancy was complicated by preterm labor at 33 weeks requiring administration of terbutaline and betamethasone. At presentation, twin A had bilateral eye discharge, erythema, and swelling medial to the medial canthi as well as nasal obstruction. Computed tomography (CT) showed classic bilateral cystic masses in the inferior meatus. The diagnosis of bilateral infected congenital dacryocystoceles was made. Twin B initially presented with only bilateral eye discharge and CT showed a dilated NLD system. Twin B subsequently developed early signs of bilateral dacryocystoceles the following day. Both patients underwent lacrimal probing and endoscopic marsupialization of the dacryocystoceles. Biopsies were consistent with dacryocystocele. Dacryocystocele is a common presentation of unresolved neonatal NLD obstruction. This case report in a set of identical twins is an argument for a genetic basis for the formation of this lesion.

Chromatin decondensation and nuclear reprogramming by nucleoplasmin.

Somatic cell nuclear cloning has repeatedly demonstrated striking reversibility of epigenetic regulation of cell differentiation. Upon injection into eggs, the donor nuclei exhibit global chromatin decondensation, which might contribute to reprogramming the nuclei by derepressing dormant genes. Decondensation of sperm chromatin in eggs is explained by the replacement of sperm-specific histone variants with egg-type histones by the egg protein nucleoplasmin (Npm). However, little is known about the mechanisms of chromatin decondensation in somatic nuclei that do not contain condensation-specific histone variants. Here we found that Npm could widely decondense chromatin in undifferentiated mouse cells without overt histone exchanges but with specific epigenetic modifications that are relevant to open chromatin structure. These modifications included nucleus-wide multiple histone H3 phosphorylation, acetylation of Lys 14 in histone H3, and release of heterochromatin proteins HP1beta and TIF1beta from the nuclei. The protein kinase inhibitor staurosporine inhibited chromatin decondensation and these epigenetic modifications with the exception of H3 acetylation, potentially linking these chromatin events. At the functional level, Npm pretreatment of mouse nuclei facilitated activation of four oocyte-specific genes from the nuclei injected into Xenopus laevis oocytes. Future molecular elucidation of chromatin decondensation by Npm will significantly contribute to our understanding of the plasticity of cell differentiation.

Requirement of the protein B23 for nucleolar disassembly induced by the FRGY2a family proteins.

In Xenopus somatic cell nuclear cloning, the nucleoli of donor nuclei rapidly and almost completely disappear in egg cytoplasm. We previously showed that the germ cell-specific proteins FRGY2a and FRGY2b were responsible for this unusually drastic nucleolar disassembly. The nucleolar disassembly occurs without inhibition of pre-rRNA transcription, a well known trigger for nucleolar segregation, and the mechanism for the nucleolar disassembly by FRGY2a and FRGY2b remains largely unknown. In this study, we searched for FRGY2a-interacting proteins and investigated the functional consequences of their interactions through a series of experiments. We showed that during the nucleolar disassembly, FRGY2a localized to the nucleoli of isolated nuclei and was capable of disassembling purified nucleoli, suggesting a direct interaction between FRGY2a and nucleolar components. Using a His tag pulldown approach, we identified the abundant and multifunctional nucleolar protein B23 as a potential target of FRGY2a and its related human protein YB1. A specific interaction between FRGY2a/YB1 and B23 was confirmed by co-immunoprecipitation. Finally, B23 knockdown using short interfering RNA and a subsequent add-back experiment confirmed that B23 was necessary for nucleolar disassembly by YB1. We propose that FRGY2a and YB1 disassemble nucleoli by sequestering B23, which is associated with pre-ribosomes and other structurally important nucleolar components.

Reversible disassembly of somatic nucleoli by the germ cell proteins FRGY2a and FRGY2b.

Egg cytoplasm has the capability to reprogramme differentiated somatic nuclei, as shown by nuclear transplantation in animal cloning. The nucleoli of donor nuclei are rapidly disassembled on injection into interphase eggs and are correctly reassembled when donor transcription initiates in the early embryos of frogs and mammals, recapitulating the physiological nucleolar dynamics of early embryogenesis. This is one of the most remarkable structural reorganizations of somatic nuclei in nuclear cloning. Despite the long history of nuclear cloning, almost nothing is known about the molecular mechanism of nucleolar disassembly in egg cytoplasm. Here we show that the Xenopus germ cell proteins FRGY2a and FRGY2b reversibly disassemble somatic nucleoli in egg cytoplasm, independently of continuing ribosomal RNA transcription. The carboxy-terminal domain of FRGY2a, which localizes to the nucleoli, is sufficient for nucleolar disassembly in transfected cells. Our results show that a single protein fragment can trigger reversible disassembly of the complex nucleolar structure.