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Biomedical subjects

Michael J Rossi

Publications and source records attributed to Michael J Rossi.

7 recordsLinked to original sources
PubMed2006

Potent antitumor activity of a novel cationic pyridinium-ceramide alone or in combination with gemcitabine against human head and neck squamous cell carcinomas in vitro and in vivo.

In this study, a cationic water-soluble ceramide analog L-threo-C6-pyridinium-ceramide-bromide (L-t-C6-Pyr-Cer), which exhibits high solubility and bioavailability, inhibited the growth of various human head and neck squamous cell carcinoma (HNSCC) cell lines at low IC50 concentrations, independent of their p53 status. Consistent with its design to target negatively charged intracellular compartments, L-t-C6-Pyr-Cer accumulated mainly in mitochondria-, and nuclei-enriched fractions upon treatment of human UM-SCC-22A cells [human squamous cell carcinoma (SCC) of the hypopharynx] at 1 to 6 h. In addition to its growth-inhibitory function as a single agent, the supra-additive interaction of L-t-C6-Pyr-Cer with gemcitabine (GMZ), a chemotherapeutic agent used in HNSCC, was determined using isobologram studies. Then, the effects of this ceramide, alone or in combination with GMZ, on the growth of UM-SCC-22A xenografts in SCID mice was assessed following the determination of preclinical parameters, such as maximum tolerated dose, clearance from the blood, and bioaccumulation. Results demonstrated that treatment with L-t-C6-Pyr-Cer in combination with GMZ significantly prevented the growth of HNSCC tumors in vivo. The therapeutic efficacy of L-t-C6-Pyr-Cer/GMZ combination against HNSCC tumors was approximately 2.5-fold better than that of the combination of 5-fluorouracil/cis-platin. In addition, liquid chromatography/mass spectroscopy analysis showed that the levels of L-t-C6-Pyr-Cer in HNSCC tumors were significantly higher than its levels in the liver and intestines; interestingly, the combination with GMZ increased the sustained accumulation of this ceramide by approximately 40%. Moreover, treatment with L-t-C6-Pyr-Cer/GMZ combination resulted in a significant inhibition of telomerase activity and decrease in telomere length in vivo, which are among downstream targets of ceramide.

Animals↗
PubMed2005

Video informed consent improves knee arthroscopy patient comprehension.

PURPOSE: The purpose of this study was to test the hypothesis that video informed consent improves knee arthroscopy patient comprehension and satisfaction compared with traditional verbal informed consent. TYPE OF STUDY: Prospective, randomized controlled trial. METHODS: Consecutive patients having informed consent in preparation for knee arthroscopy by a single surgeon were stratified by educational level < or =12th grade or greater than 12th grade, then randomized to video or traditional verbal informed consent groups. Immediately after the informed consent process, patients completed an outcome questionnaire evaluating comprehension and satisfaction. RESULTS: Patients in the video group showed significantly higher comprehension (78.5%) than patients in the verbal group (65.4%) (P = .00001). In the subgroup with < or = 12th grade education level, the video patients scored 73.1% comprehension and the verbal patients only 54.2% (P = .0011). In the subgroup with greater than 12th grade education level, the video patients scored 82.3% and the verbal patients scored 72.2% (P = .0002). There was no significant difference in subjective self-assessment of satisfaction between groups. CONCLUSIONS: Video informed consent improves knee arthroscopy patient comprehension compared with traditional verbal informed consent. LEVEL OF EVIDENCE: Level I.

Adolescent↗
PubMed2005

Inhibition of growth and telomerase activity by novel cationic ceramide analogs with high solubility in human head and neck squamous cell carcinoma cells.

OBJECTIVES: Head and neck squamous cell carcinoma (HNSCC) is notoriously resistant to chemotherapy. The sphingolipid ceramide and its analogs have been demonstrated to exert antitumor activity in many cell types; however, the effectiveness of these analogs has been limited by potency and solubility. This study focuses on the effects of novel highly soluble cationic pyridinium-ceramides, alone and in combination with various chemotherapeutic agents, on cell survival, telomerase activity, and cell cycle arrest in HNSCC cell lines in vitro. METHODS: The concentration of pyridinium-ceramides and chemotherapeutic agents that inhibited cell growth by 50% (IC50) was determined by MTT cell survival assays. The cell cycle profiles were determined by flow cytometry. Telomerase activity was determined by telomerase repeat amplification protocol (TRAP) assay. RESULTS: Treatment of the human UM-SCC-22A (SCC of the hypopharynx) cells, as well as various other HNSCC cell lines, with C6-Pyr-Cer resulted in the inhibition of cell survival with an IC50 concentration of approximately 250 to 300 nM at 96 hours, whereas its IC50 was greater than 1000 nM in noncancerous Wi-38 human lung fibroblasts, and adult human epidermal keratinocytes. Moreover, treatment with C6-Pyr-Cer also resulted in cell cycle arrest in G0/G1, which correlated with a significant inhibition of telomerase activity in UM-SCC-22A cells. Additional results demonstrated that the combination of C6-Pyr-Cer with gemcitabine (GMZ) or doxorubicin (DOX), which have the lowest IC50 concentrations among various chemotherapeutic drugs in these cells, enhances the effects of these drugs in the inhibition of telomerase and cell growth. CONCLUSIONS: These data suggest that the novel C6-Pyr-Cer with high solubility and bioavailability may lead to the development of new therapeutic strategies that target telomerase for the treatment of HNSCC.

Antineoplastic Agents↗
PubMed2004

Arthroscopic visualization of the posterior compartments of the knee.

PURPOSE: The purpose of this study is to test the hypothesis that the efficacy of routine arthroscopic evaluation of the posterior compartments of the knee outweighs the morbidity or inefficiency. TYPE OF STUDY: Prospective cohort analysis. METHODS: One hundred consecutive knees underwent posteromedial and posterolateral evaluation according to an algorithm designed to maximize efficiency of technique. Loose bodies were defined as expected when preoperative imaging or arthroscopy of the rest of the knee revealed loose bodies. The number of attempts required for visualization or visualization not accomplished, morbidity (subjective femoral condylar scuffing or complications associated with the technique), and findings were recorded. RESULTS: With regard to posteromedial, directly inserting the camera (as opposed to an obdurator) resulted in instrument breakage. In this study, 82% of posteromedial compartments were visualized on the first attempt, and 3% were not visualized. We found that 66% of femoral condyles had no damage, 28% mild, 3% moderate, and 3% severe. Loose bodies were found in 4 of 11 (36%) when expected and 0 of 86 when not expected, a significant difference. Five other posteromedial positive findings were observed. With regard to posterolateral, 93% of compartments were visualized on the first attempt, directly with the camera via the anterolateral portal. All were visualized. We found that 96% of femoral condyles had no damage, 4% mild, and 0% moderate or severe. Damage occurred significantly less frequently than with posteromedial. No findings were noted. CONCLUSIONS: Despite inefficiency, we recommend an obdurator for posteromedial visualization via the anterolateral portal. Posteromedial visualization was associated with morbidity but was efficacious in some cases and is strongly recommended when loose bodies are expected. Posterolateral visualization directly with the camera and via the anterolateral portal is efficient and associated with minimal morbidity but was not efficacious in the cohort evaluated. LEVEL OF EVIDENCE: Level II.

Adolescent↗
PubMed2003

The skier's knee.

Knee injuries in skiers have unique epidemiology and distinct mechanisms. Conversely, evaluation and treatment of the skier's knee is similar to evaluation and treatment of knee injuries in other athletes. A greater understanding of the epidemiology and mechanisms of knee injuries in skiers may aid arthroscopic clinicians and related researchers treating or investigating knee injuries in both skiers and in other athletes.

Athletic Injuries↗
PubMed2002

Biochemical mechanisms of the generation of endogenous long chain ceramide in response to exogenous short chain ceramide in the A549 human lung adenocarcinoma cell line. Role for endogenous ceramide in mediating the action of exogenous ceramide.

Treatment of A549 cells with C(6)-ceramide resulted in a significant increase in the endogenous long chain ceramide levels, which was inhibited by fumonisin B1 (FB1), and not by myriocin (MYR). The biochemical mechanisms of generation of endogenous ceramide were investigated using A549 cells treated with selectively labeled C(6)-ceramides, [sphingosine-3-(3)H]d-erythro-, and N-[N-hexanoyl-1-(14)C]d-erythro-C(6)-ceramide. The results demonstrated that (3)H label was incorporated into newly synthesized long chain ceramides, which was inhibited by FB1 and not by MYR. Interestingly, the (14)C label was not incorporated into long chain ceramides. Taken together, these results show that generation of endogenous ceramide in response to C(6)-ceramide is due to recycling of the sphingosine backbone of C(6)-ceramide via deacylation/reacylation and not due to the elongation of its fatty acid moiety. Moreover, the generation of endogenous long chain ceramide in response to C(6)-ceramide was completely blocked by brefeldin A, which causes Golgi disassembly, suggesting a role for the Golgi in the metabolism of ceramide. In addition, the generation of endogenous ceramide in response to short chain exogenous ceramide was induced by d-erythro- but not l-erythro-C(6)-ceramide, demonstrating the stereospecificity of this process. Interestingly, several key downstream biological activities of ceramide, such as growth inhibition, cell cycle arrest, and modulation of telomerase activity were induced by d-erythro-C(6)-ceramide, and not l-erythro-C(6)-ceramide (and inhibited by FB1) in A549 cells, suggesting a role for endogenous long chain ceramide in the regulation of these responses.

Adenocarcinoma↗