25 research outputs found
Upregulation of Cyclooxygenase-2/Prostaglandin E2 (COX-2/PGE2) Pathway Member Multiple Drug Resistance-Associated Protein 4 (MRP4) and Downregulation of Prostaglandin Transporter (PGT) and 15-Prostaglandin Dehydrogenase (15-PGDH) in Triple-Negative Breast Cancer
Emergence of HPV16-Positive Oropharyngeal Cancer in Black Patients Over Time: University of Maryland 1992–2007
Definitive cetuximab-based (CRT-CX) vs. non-cetuximab based chemoradiation (CRT) in older patients with squamous cell carcinoma of the head and neck (HNSCC): Analysis of the SEER-Medicare linked database.
Ionizing Radiation Induces Delayed Hyperrecombination in Mammalian Cells
Exposure to ionizing radiation can result in delayed effects that can be detected in the progeny of an irradiated cell multiple generations after the initial exposure. These effects are described under the rubric of radiation-induced genomic instability and encompass multiple genotoxic endpoints. We have developed a green fluorescence protein (GFP)-based assay and demonstrated that ionizing radiation induces genomic instability in human RKO-derived cells and in human hamster hybrid GM10115 cells, manifested as increased homologous recombination (HR). Up to 10% of cells cultured after irradiation produce mixed GFP(+/−) colonies indicative of delayed HR or, in the case of RKO-derived cells, mutation and deletion. Consistent with prior studies, delayed chromosomal instability correlated with delayed reproductive cell death. In contrast, cells displaying delayed HR showed no evidence of delayed reproductive cell death, and there was no correlation between delayed chromosomal instability and delayed HR, indicating that these forms of genome instability arise by distinct mechanisms. Because delayed hyperrecombination can be induced at doses of ionizing radiation that are not associated with significantly reduced cell viability, these data may have important implications for assessment of radiation risk and understanding the mechanisms of radiation carcinogenesis
EP4 and Class III β-Tubulin Expression in Uterine Smooth Muscle Tumors: Implications for Prognosis and Treatment
The microtubule-stabilizing agent docetaxel in combination with gemcitabine represents one of the most effective regimens against the aggressive gynecologic tumor leiomyosarcoma (LMS). Upregulation of class III β-tubulin has previously been shown to confer taxane resistance in a variety of human cancers. Prostaglandin E2 receptor EP4 is linked to progression of a variety of human cancers and may represent a novel target for tumor inhibition in LMS. We evaluated the hypotheses that EP4 and class III β-tubulin have increased expression in LMS in comparison to normal myometrium or benign tumors and that expression of class III β-tubulin correlates with resistance to taxanes and poor clinical outcome. Gene expression was examined using TCGA data and correlated with clinicopathologic outcome which demonstrated that class III β-tubulin is more highly expressed in more aggressive sarcomas with EP4 being widely expressed in all subtypes of sarcoma. Immunohistochemistry for EP4 and class III β-tubulin was performed on patients with LMS, leiomyomatosis/STUMP, leiomyoma, and normal myometrium. Expression of EP4 and class III β-tubulin were characterized for cell lines SK-UT-1, SK-UT-1B, and PHM-41 and these cell lines were treated with docetaxel alone and in combination with EP4 inhibitors. In taxane-resistant cell lines that overexpress class III β-tubulin and EP4, treatment with EP4 inhibitor resulted in at least 2-fold sensitization to docetaxel. Expression of class III β-tubulin and EP4 in LMS may identify patients at risk of resistance to standard chemotherapies and candidates for augmentation of therapy through EP4 inhibition
HDAC Inhibitor Entinostat Restores Responsiveness of Letrozole-Resistant MCF-7Ca Xenografts to Aromatase Inhibitors through Modulation of Her-2
Venous Thromboembolic Complications of Lung Transplantation: A Contemporary Single-Institution Review
The incidence and consequences of deep venous thrombosis (DVT) and pulmonary embolism (PE) have not been described recently in lung transplant recipients. We sought to characterize DVT and PE in a contemporary series of lung transplant recipients and describe their association with clinical outcomes.
The records of all lung transplant recipients from July 1, 2008, to June 30, 2013, were reviewed and analyzed. DVT was diagnosed by venous duplex ultrasonography. PE was diagnosed by computed tomography angiography, nuclear ventilation/perfusion scanning, or pulmonary angiography.
The study comprised 117 patients who underwent 123 transplants. The median age was 63 years (range, 17 to 77 years). Forty-five patients (39%) had evidence of lower extremity DVT, 53 (45%) had no evidence of lower extremity DVT, and 19 (16%) were not tested. Fifty-three (45%) had evidence of upper extremity DVT, 30 (26%) had no evidence of upper extremity DVT, and 34 (29%) were not tested. Eighteen (15%) had evidence of PE, 82 (70%) had no evidence of PE, and 17 (15%) were not tested. A multivariable, stepwise Cox proportional hazards model revealed that the presence of lower extremity DVT (hazard ratio, 2.43; 95% confidence interval, 1.29 to 4.64), use of cardiopulmonary bypass (hazard ratio, 2.21; 95% confidence interval, 1.04 to 4.68), and unilateral lung transplantation (hazard ratio, 2.13; 95% confidence interval, 1.07 to 4.25) were associated with diminished survival.
The incidence of DVT and PE in lung transplant recipients is high. Posttransplant surveillance and treatment based on findings are warranted