Impact of Artifacts Caused by Intraoral Dental Materials in Magnetic Resonance Imaging

Objective: To evaluate the characteristics of artifacts produced by various intraoral dental materials in magnetic resonance imaging sequences and assess their impact on the diagnostic quality of the resultant images. Material and Methods: A clinical examination was conducted on forty-six patients who underwent magnetic resonance imaging for various brain pathologies. Parameters were recorded, including the location, span, and type of intraoral dental material. The impact of these artifacts on the diagnostic quality of the resultant image sequences was assessed. The reliability of the intra- and interobserver was calculated, and Fischer\u27s exact test was applied. P-value <0.05 was considered statistically significant. Results: The most common signal intensity artifact observed was hypointense with hyperintense rim artifacts in FLAIR (95.5%). The most common shape of the artifacts observed was circular/void shape (84.4%). There was a statistically significant difference between the various classes of intraoral dental materials and diagnostic acceptability (p=0.017). In the present study, 28% of the study population images were graded diagnostically unacceptable in the sequences evaluated (FLAIR 37.8%, T2 3.3%, SWI 24.4%, DWI 25%). Conclusion: Dental material artifacts interfered with the interpretation of magnetic resonance imaging at varying levels of diagnostic acceptability depending on the indication for which the imaging was performed

Impact of Artifacts Caused by Intraoral Dental Materials in Magnetic Resonance Imaging

Objective: To evaluate the characteristics of artifacts produced by various intraoral dental materials in magnetic resonance imaging sequences and assess their impact on the diagnostic quality of the resultant images. Material and Methods: A clinical examination was conducted on forty-six patients who underwent magnetic resonance imaging for various brain pathologies. Parameters were recorded, including the location, span, and type of intraoral dental material. The impact of these artifacts on the diagnostic quality of the resultant image sequences was assessed. The reliability of the intra- and interobserver was calculated, and Fischer's exact test was applied. P-value <0.05 was considered statistically significant. Results: The most common signal intensity artifact observed was hypointense with hyperintense rim artifacts in FLAIR (95.5%). The most common shape of the artifacts observed was circular/void shape (84.4%). There was a statistically significant difference between the various classes of intraoral dental materials and diagnostic acceptability (p=0.017). In the present study, 28% of the study population images were graded diagnostically unacceptable in the sequences evaluated (FLAIR 37.8%, T2 3.3%, SWI 24.4%, DWI 25%). Conclusion: Dental material artifacts interfered with the interpretation of magnetic resonance imaging at varying levels of diagnostic acceptability depending on the indication for which the imaging was performed

Lower-intensity CPX-351 plus venetoclax induction for adults with newly diagnosed AML unfit for intensive chemotherapy

Preclinical data suggest a rationale for combining CPX-351, a dual-drug liposomal encapsulation of daunorubicin and cytarabine, with venetoclax, a B-cell lymphoma-2 inhibitor. This phase 1b study evaluated lower-intensity CPX-351 combined with venetoclax in adults with acute myeloid leukemia (AML) considered unfit/ineligible for intensive chemotherapy. In a dose-exploration phase using a 3+3 design, patients received stepwise dosing of CPX-351 IV on days 1 and 3 plus venetoclax 400 mg orally on days 2 to 21 per cycle to determine the recommended phase 2 dose (RP2D) for this combination. During the expansion phase, additional patients received CPX-351 plus venetoclax at the identified RP2D. The primary end points were the RP2D and safety of CPX-351 combined with venetoclax. Secondary end points included preliminary efficacy and pharmacokinetics. Overall, 35 patients were enrolled in the study. A RP2D of CPX-351 30 units/m2 (daunorubicin 13.2 mg/m2 and cytarabine 30 mg/m2) plus venetoclax 400 mg was established. The safety profile of the combination was consistent with the known safety profiles of CPX-351 and venetoclax. Complete remission (CR)/CR with incomplete hematologic recovery (CRi) was achieved by 17 of 35 patients (49%), all after cycle 1; of these, 14 were negative for measurable residual disease. CR was achieved by 1 of 8 patients (13%) with a mutation in TP53, and CR/CRi was achieved by 15 of 26 patients (58%) with wild-type TP53. This study highlights that lower-intensity therapy of CPX-351 plus venetoclax as induction therapy provides a well-tolerated treatment option in adults with AML deemed unfit for intensive chemotherapy. This trial was registered at www.ClinicalTrials.gov as #NCT04038437

Abstract LB-101: Targeting pancreatic cancer stroma with Palmatine, a novel compound from herbal supplement.

Abstract Pancreatic ductal adenocarcinoma is the fourth leading cause of cancer related deaths with 5-year survival rates less than 6%. Survival periods with gemcitabine in combination with various agents average over 6 months. Desmoplasia is a striking feature of pancreatic cancer. It is characterized by formation of dense stroma surrounding the tumor. This dense stroma serves as a therapeutic barrier for many chemotherapeutic drugs, in turn decreasing their efficacy. Pancreatic stellate cells (PSCs) have been reported to be involved in the observed desmoplastic reaction. Therefore targeting this stroma can be an alternate approach to pancreatic cancer. Previous studies from our laboratory showed that Nexrutine, a herbal supplement inhibits proliferation of multiple pancreatic cancer cells through modulation of Stat3/NFκB/Cox-2 signaling and reduced the number of animals developing fibrosis in vivo. To the best of our knowledge, the effect of Nexrutine or its active components on pancreatic stroma has not been studied. In this study we evaluated the effect of Nexrutine and Palmatine, an active component of Nexrutine, for its ability to target the stroma. Our studies show for the first time that Palmatine (i) inhibits proliferation of PSCs as well as the tumor cells; (ii) inhibits hedgehog signaling as evidenced by GLI expression and reporter activity; (iii) modulates expression and activity of downstream targets of GLI including Patched1, IKKB-ε and anti-apoptotic protein Survivin. Remarkably Palmatine treatment inhibits invasive ability of PSCs that is associated with reduced levels of COL1A1. Overall this is the first study reporting the ability of Palmatine to modulate Hh signaling and may have utility either alone or in conjunction with Gemcitabine for treatment of pancreatic ductal adenocarcinoma. Supported by NCCAM (AT 005513-01A1 and AT 007448l; APK). Citation Format: Divya Chakravarthy, Jingjing Gong, Rosa F. Hwang, Addanki Pratap Kumar. Targeting pancreatic cancer stroma with Palmatine, a novel compound from herbal supplement. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-101. doi:10.1158/1538-7445.AM2013-LB-101</jats:p

Abstract 5392: Metabolic profiling of castrate-resistant prostate cancer reveals novel role for bile acids in driving castration resistance.

Abstract The 5-year survival for metastatic castrate-resistant prostate cancer patients is less than 30% despite significant progress in the understanding of prostate cancer biology and development of novel therapeutic agents. A major contributing factor for the observed low survival rate of patients with castrate resistant disease is the lack of knowledge regarding metabolic alterations and their underlying contributions during development of castrate-resistant phenotype. Studies conducted in our laboratory and others identified a potential role for 2-methoxyestradiol (2-ME2) to prevent prostate cancer development and progression through inhibition of the anti-apoptotic protein FLIP. The goal of the current study was to identify biochemical changes in response to castration and treatment with 2-ME2 in serum from transgenic adenocarcinoma of mouse prostate (TRAMP) mice using mass spectrometry based global profiling. We identified a total of 54 biochemicals of which 16 increased and 38 decreased in castrated animals compared to sham-castration. Treatment of sham-castrated animals with low and high doses of 2-ME2 altered 91 and 145 biochemicals respectively. On the other hand treatment of castrated animals modulated 89 and 106 biochemicals. Cumulative analysis of these data also identified alteration of 60 biochemicals associated with castration effect, 149 with treatment and 70 interactions between castration and treatment effects. Castration affected metabolites involved in variety of metabolic pathways including lipid, oxidative stress, energetics and bile acid. Given the data showing enhanced expression of FLIP in castrate-resistant prostate tumors and upregulation of bile acids in patients undergoing androgen deprivation therapy, we examined the activation of FLIP in prostate cancer cells in response to deoxycholic acid (DCA). Our data suggests that transcriptional activity of FLIP was higher in PC-3 cells treated with DCA. To the best of our knowledge, this is the first report demonstrating global metabolomic profiling of serum in response to castration and provide a framework for therapeutic targeting of bile acid metabolism. Supported by NIH CA 135451 (APK). Citation Format: Divya Chakravarthy, Paul Rivas, Brian Keppler, Jianhua Ruan, Rita Ghosh, Addanki Pratap Kumar. Metabolic profiling of castrate-resistant prostate cancer reveals novel role for bile acids in driving castration resistance. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5392. doi:10.1158/1538-7445.AM2013-5392 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.</jats:p