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Columbus, OH, United States

Poi M.J.,Richard J Solove Research Institute | Poi M.J.,Ohio State University | Knobloch T.J.,Ohio State University | Sears M.T.,Ohio State University | And 4 more authors.
Anticancer Research | Year: 2014

Background/Aim: While aberrant expression of cyclin-dependent kinase-4 (CDK4) has been found in squamous cell carcinoma of the head and neck (SCCHN), the associations between CDK4 and its regulators, namely, cyclin D1, cyclin E, gankyrin, SEI1, and BMI1 in gene expression remain to be explored. Herein we investigated the mRNA profiles of these oncogenes and their interrelations in different oral lesion tissues. Materials and Methods: Thirty SCCHN specimens and patient-matched high at-risk mucosa (HARM) and 16 healthy control specimens were subjected to quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analyses. Results: The mRNA levels of CDK4, cyclin D1, gankyrin, SEI1, BMI1 were significantly elevated in both HARM and SCCHN (in comparison with control specimens), and statistically significant correlations were found among these markers in gene expression. Conclusion: Up-regulation of CDK4 and its regulators takes place in oral cancer progression in a coordinate manner, and HARM and SCCHN share a similar molecular signature within the CDK4-pRB pathway. Source

Zuo T.,Richard J Solove Research Institute | Liu T.-M.,Richard J Solove Research Institute | Lan X.,Richard J Solove Research Institute | Weng Y.-I.,Richard J Solove Research Institute | And 13 more authors.
Cancer Research | Year: 2011

Trimethylation of histone 3 lysine 27 (H3K27me3) is a critical epigenetic mark for the maintenance of gene silencing. Additional accumulation of DNA methylation in target loci is thought to cooperatively support this epigenetic silencing during tumorigenesis. However, molecular mechanisms underlying the complex interplay between the two marks remain to be explored. Here we show that activation of PI3K/AKT signaling can be a trigger of this epigenetic processing at many downstream target genes. We also find that DNA methylation can be acquired at the same loci in cancer cells, thereby reinforcing permanent repression in those losing the H3K27me3 mark. Because of a link between PI3K/AKT signaling and epigenetic alterations, we conducted epigenetic therapies in conjunction with the signaling-targeted treatment. These combined treatments synergistically relieve gene silencing and suppress cancer cell growth in vitro and in xenografts. The new finding has important implications for improving targeted cancer therapies in the future. ©2011 AACR. Source

Poi M.J.,Richard J Solove Research Institute | Berger M.,Richard J Solove Research Institute | Lustberg M.,Ohio State University | Layman R.,Ohio State University | And 5 more authors.
Supportive Care in Cancer | Year: 2013

Purpose: As the result of a recent national shortage in paclitaxel, some patients who were receiving or scheduled to receive weekly paclitaxel were converted to every 3-week (q3w) docetaxel with granulocyte colony-stimulating factor support. Our institution noted higher than expected incidence of severe skin toxicity events attributable to docetaxel during the shortage period among our breast cancer patients. In this report, we summarize the clinical course of the first five cases, review the literature surrounding docetaxel-induced skin toxicity, and offer possible prevention and treatment strategies to improve docetaxel tolerability. Methods: The observation period for this case series was August 1 through October 21, 2011. All patients treated with docetaxel were identified from our electronic medical record. Operable stage I-III breast cancer patients who received ≥1 dose of docetaxel monotherapy at 75-100 mg/m2 q3w were included in this study. The cases of grade 3-4 docetaxel-induced skin toxicities identified by the treating oncologists were then contacted and signed an informed consent through an Institutional Review Board-approved protocol. Results: Thirty-four patients met the inclusion criteria. Five patients (14.7 %) experienced grade 3 skin toxicity events attributable to docetaxel, a significantly higher rate than previously reported for docetaxel dosed at 75-100 mg/m2. Conclusions: Docetaxel-induced dermatologic toxicity is well characterized; nonetheless, its etiology is largely unknown and evidence-based prevention and management strategies are lacking. This report shows that the use of docetaxel 75-100 mg/m2 q3w subsequent to dose-dense doxorubicin and cyclophosphamide regimen can lead to unacceptable rate of severe skin toxicity. © 2013 Springer-Verlag Berlin Heidelberg. Source

Miller E.D.,Richard J Solove Research Institute | Xu-Welliver M.,Richard J Solove Research Institute | Haglund K.E.,Richard J Solove Research Institute
Journal of Surgical Oncology | Year: 2015

For nearly half a decade, surgery and radiation therapy have been used in combination to achieve the goal of limb preservation in extremity soft tissue sarcoma, with success rates in excess of 90%. Common decision points in therapeutic radiation delivery for sarcoma are discussed, including preoperative versus postoperative irradiation, the postoperative boost, and when irradiation might be unnecessary. We describe specialized techniques, such as brachytherapy and intraoperative irradiation. The data driving current practice is summarized. J. Surg. Oncol. 2015 111:599-603. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc. Source

Dziegielewski P.T.,Ohio State University | Dziegielewski P.T.,Richard J Solove Research Institute | Teknos T.N.,Ohio State University | Teknos T.N.,Richard J Solove Research Institute | And 13 more authors.
JAMA Otolaryngology - Head and Neck Surgery | Year: 2013

IMPORTANCE: Because treatment for oropharyngeal squamous cell carcinoma (OPSCC), especially in patients of older age, is associated with decreased patient quality of life (QOL) after surgery, demonstration of a less QOL-impairing treatment technique would improve patient satisfaction substantially. OBJECTIVE: To determine swallowing, speech, and QOL outcomes following transoral robotic surgery (TORS) for OPSCC. DESIGN, PARTICIPANTS, AND SETTING: This prospective cohort study of 81 patients with previously untreated OPSCC was conducted at a tertiary care academic comprehensive cancer center. INTERVENTIONS: Primary surgical resection via TORS and neck dissection as indicated. MAIN OUTCOMES AND MEASURES: Patients were asked to complete the Head and Neck Cancer Inventory (HNCI) preoperatively and at 3 weeks as well as 3, 6, and 12 months postoperatively. Swallowing ability was assessed by independence from a gastrostomy tube (G-tube). Clinicopathologic and follow-up data were also collected. RESULTS: Mean follow-up time was 22.7 months. The HNCI response rates at 3 weeks and 3, 6, and 12 months were 79%, 60%, 63%, and 67% respectively. There were overall declines in speech, eating, aesthetic, social, and overall QOL domains in the early postoperative periods. However, at 1 year post TORS, scores for aesthetic, social, and overall QOL remained high. Radiation therapy was negatively correlated with multiple QOL domains (P < .05 for all comparisons), while age older than 55 years correlated with lower speech and aesthetic scores (P < .05 for both). Human papillomavirus status did not correlate with any QOL domain. G-tube rates at 6 and 12 months were 24% and 9%, respectively. Greater extent of TORS (>1 oropharyngeal site resected) and age older than 55 years predicted the need for a G-tube at any point after TORS (P < .05 for both). CONCLUSIONS AND RELEVANCE: Patients with OPSCC treated with TORS maintain a high QOL at 1 year after surgery. Adjuvant treatment and older age tend to decrease QOL. Patients meeting these criteria should be counseled appropriately. Copyright 2013 American Medical Association. All rights reserved. Source

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