Role and regulation of GLUT1/3 during oral cancer progression and therapy resistance.

OBJECTIVE: This study aimed to determine whether glucose transporter-1/3 (GLUT1/3) increased expression could contribute to oral tumor severity. Furthermore, this study detected whether GLUT1/3 mRNA/protein was associated with oncogenic transcription factors (HIF1α, AP1 and NFκB) and whether by blocking GLUT1 along with cisplatin could sensitize drug-resistant OSCC cells. DESIGN: We used 120 post-operated human tissue samples, including 35 primary tumors (PT), 43 invasive tumors (N1-3), 17 recurrent chemoradiation-resistant tumors (RCRT), and 25 PT-adjacent normal tissues (AN). The cisplatin-resistant (CisR-SCC4/9) cells were generated using a drug escalation strategy from parental SCC4/9 cells. The BAY-876 treatment blocked GLUT1 in OSCC cells. Western Blot, Immunohistochemistry, and reverse transcription polymerase chain reaction (RT-PCR) were used to detect various proteins and mRNA. Cell survival was determined by MTT assay. RESULTS: GLUT1/3 expression was observed more in PT over AN tissue (PT > AN), N1-3 > PT, and .RCRT > PT. GLUT1 expression was maximum in the RCRT group and CisR-SCC4/9 cells over their parental counterpart, linked with tumor size (p=0.0037) and loco-regional invasiveness (p=0.0422). GLUT1/3 mRNA/protein was correlated (positively) with oncogenic transcription factors (TFs) like HIF1α, AP1 and NFκB. We found the degree of positive correlation of these TFs with GLUT1/3 was in the order c-Jun > HIF1α > Fra-2 > NFκB > c-Fos. Treatment of BAY-876 and cisplatin-induced cell death in both CisR-SCC4/9 cells, possibly by triggering apoptosis and autophagy. CONCLUSION: Collectively, our results demonstrated increased GLUT1/3 overexpression linked with oral tumor severity like invasion and therapy resistance, and it was powered mainly by c-Jun (AP1). Blocking GLUT1 receptors and cisplatin application can sensitize CisR-OSCC cells.

Crystallization and Rheology of Mono- and Diglycerides and Their Role in Stabilization of Emulsion Droplets in Model Topical Ointments.

The crystallization behavior of commercial mono- and diglycerides (MDG) in paraffin oil is studied to develop an in-depth understanding of the polymorphic transitions useful for the physical stability of petroleum oil-based topical emulsions. Optical microscopy and differential scanning calorimetry measurements showed the formation of plate-like and spherulite crystals at high and low temperatures, in sequence, while cooling a solution of MDG dissolved in oil. High-resolution NMR and X-ray scattering demonstrate that 1-monoglycerides (mixture of 1-glyceride monostearate and 1-glyceride monopalmitate) cocrystallize to an inverse-lamellar structure (Lα polymorph) that mainly forms plate-like crystals at a higher temperature. The Lα polymorph is seen to exist up to room temperature during the cooling process. At lower temperatures, 1,3-diglycerides (mixture of 1,3-glyceryl distearate and 1,3-glyceryl dipalmitate) crystallize into ß-polymorphs that form spherulites. The spherulites tend to assemble into elongated strands via aggregation, leading to the formation of a percolating network structure. The sizes of both types of crystals decrease with an increasing cooling rate, leading to a higher mechanical modulus due to the increased network connectivity of spherulites. In an emulsion, monoglycerides in the form of Lα polymorphs having plate-like crystal morphology show a higher affinity to the polar liquid/oil interface, thereby providing better interfacial stability compared to the spherulitic ß-polymorphs. However, diglycerides in the form of spherulites form bulk network structures which provide network stabilization to the suspended droplets. This work demonstrates that MDG, a commercially available ingredient that combines the differential functionality of monoglycerides and diglycerides, is an effective, bifunctional, emulsifying agent for petrolatum-based topical emulsions.

Prediction of significant hyperbilirubinemia in term neonates by early non-invasive bilirubin measurement.

BACKGROUND: Neonatal jaundice is a common problem. We evaluated the utility and best cut-off values of 24-and 48-hour transcutaneous bilirubin indices (TcBI) in predicting subsequent significant hyperbilirubinemia and evaluated various associated maternal and fetal risk factors. METHODS: TcBI at 24 and 48 hours and serum bilirubin levels at 72 hours of age were obtained for healthy, term, appropriate for gestational age neonates. Neonates with prematurity, birth weight <2500 g, ABO or Rh incompatibility, onset of clinical jaundice <24 hours, clinical suspicion of septicemia, positive pressure ventilation at birth, admission in neonatal intensive care unit and contraindications for BiliChek were excluded. Twently-four and 48-hour TcB indices were assessed as predictors of subsequent hyperbilirubinemia, defined as serum bilirubin >17 mg/dL after 72 hours of life and various cut-offs, and were evaluated by calculating sensitivity, specificity and predictive values. RESULTS: Of 500 newborns, 4.6% had significant hyperbilirubinemia, 27% had TcBI (mg/dL) <5 at 24 hours, and 27.4% had TcBI <8 at 48 hours. None of them had subsequent hyperbilirubinemia (100% negative predictive value). The percentage of newborns with subsequent hyperbilirubinemia increased from 3.4% to 13.2% as their 24-hour TcBI increased from 6 to above 9 mg/dL and from 4.2% to 7.4% as their 48-hour TcBI increased from 8 to above 11 mg/dL. The best cut-off value was TcBI (mg/dL) 7 (odd ratio=4.86, 95% confidence interval: 1.66-15.22) at 24 hours and 10 (odd ratio=2.87, 95% confidence interval: 1.04-8.29) at 48 hours. Area under the receiver operating characteristic curve for 24- and 48-hour measurements was 0.750 and 0.715, respectively. Maternal premature rupture of membranes, deep transverse arrest, post-date pregnancy, and fetal distress were significant risk factors for hyperbilirubinemia. CONCLUSIONS: Twenty-four and 48-hour TcB indices are good predictors of subsequent hyperbilirubinemia. Twenty-four-hour TcBI had better predictive ability than 48-hour TcBI.