Adipose derived mesenchymal stem cell secretome formulation as a biotherapeutic to inhibit growth of drug resistant triple negative breast cancer.

In the present study, a protocol was developed for processing of human adipose derived mesenchymal stem cell secretome formulation of varying concentration. Its molecular composition was evaluated, and its effectiveness in vitro using breast cancer cell lines, and in vivo in a nude mice breast cancer model was studied to determine its role in suppressing triple negative breast cancer in a dose dependent manner. Because the secretome could have value as an add-on therapy along with a current drug, the effectiveness of the secretome both in monotherapy and in combination therapy along with paclitaxel was evaluated. The results showed significant cell kill when exposed to the secretome above 20 mg/ml at which concentration there was no toxicity to normal cells. 70 mg/ml of SF showed 90 ± 10% apoptosis and significant decrease in CD44+/CD24-, MDR1+ and PDL-1+ cancer cells. In vivo, the tumor showed no growth after daily intra tumor injections at 50 mg/ml and 100 mg/ml doses whereas substantial tumor growth occurred after saline intra tumor injection. The study concludes that SF is a potential biotherapeutic for breast cancer and could be used initially as an add-on therapy to other standard of care to provide improved efficacy without other adverse effects.

Exploring the utility of fibreoptic endoscopic evaluation of swallowing in young children- A comparison with videofluoroscopy.

OBJECTIVES/HYPOTHESIS: In adults, fibreoptic endoscopic evaluation of swallowing (FEES) has established its place in the assessment of dysphagia and aspiration vis-à-vis the current gold standard, videofluoroscopic swallow study (VFSS), almost at parity. However, in children with quite a different set of factors in play, its role is not certain. The primary objective was to measure the accuracy of FEES in young children with dysphagia, compared to VFSS. The secondary objective was to correlate other endoscopic findings with aspiration in videofluoroscopy. STUDY DESIGN: Prospective, observational. METHODOLOGY: Sixty-five children, aged 0.4-36 months with suspected oropharyngeal dysphagia and aspiration underwent FEES and VFSS. Sensitivity, specificity, positive predictive value, negative predictive value, accuracy and diagnostic agreement of FEES were calculated using VFSS as the gold standard. To test the statistical significance of the difference in two measurements, Mc Nemar's Chi-square test was used and to test the agreement between FEES and VFSS, Kappa value was calculated. To test the statistical significance of the association of endoscopic findings with VFSS findings, Chi-square test was used. RESULTS: FEES performed in young children was found to be less sensitive (50%) but more specific of aspiration (82%) with an accuracy of 77% in comparison with VFSS. The reverse was true of penetration (81%, 44% and 59% respectively). The agreement between FEES and VFSS in young children, on all parameters were low (k = 0.061-0.302). Endoscopic findings such as glottic secretions (P = 0.02), weak or diminished laryngeal adductor reflex (LAR) (P = 0.001) and penetration (P = 0.01) were significantly associated with aspiration in VFSS. Excessive secretions in the hypopharynx had a stronger correlation with oesophageal dysmotility (P = 0.02) than pharyngeal dysphagia (P = 0.05). CONCLUSION: FEES in young children appears to have a low agreement with VFSS unlike in adults. Aspiration observed in FEES is likely to be significant since specificity is high. FEES negative for aspiration may be interpreted taking into account, the aspiration risk of the subject and/or other endoscopic risk factors (penetration, weak/absent LAR & glottic secretions), if VFSS is not a viable alternative.

Injectable deferoxamine nanoparticles loaded chitosan-hyaluronic acid coacervate hydrogel for therapeutic angiogenesis.

In this study, an injectable chitosan-hyaluronic acid (CS-HA) based hydrogel was designed incorporating pro-angiogenic molecule, deferoxamine loaded PLGA nanoparticles (DFO NPs), for enhancing angiogenesis. DFO-NPs were prepared by double emulsion solvent diffusion technique and characterized for their physicochemical properties. The DLS and SEM analysis showed an average particle size of 220±71nm with spherical morphology and the encapsulation efficiency was found to be 30±5%. An ECM mimicking chitosan-hyaluronic acid (CS-HA) coacervate hydrogel was prepared. Both free DFO and DFO NPs were entrapped into the prepared CS-HA composite hydrogel. The hydrogels were characterized by SEM, FTIR and Rheology. Addition of DFO NPs did not affect the injectablility and flowability of developed hydrogels. In vitro DFO release from the prepared composite hydrogels showed controlled release over a period of 10days. Both the hydrogel systems showed excellent cyto-compatability and good cell proliferation for rASCs as well as HUVECs. The DFO and DFO NPs loaded composite hydrogels revealed effective tube formation in comparison with control hydrogels without DFO and DFO NPs. The in vivo angiogenic evaluation of the free DFO and DFO NPs (0.025%w/w) loaded composite hydrogels were studied by injecting the developed hydrogel subcutaneously into mice for 2-4 weeks. The DFO NPs loaded composite hydrogel had enhanced neovascularization when compared to control gels. Thus, the developed DFO NPs loaded composite hydrogel could potentially be used for therapeutic angiogenesis.

Easy and Safe Method for Facial Nerve Identification in Parotid Surgery.

Background A safe and easy anatomical landmark is proposed to identify the facial nerve in parotid surgery. The facial nerve forms the center point between the base of the styloid process and the origin of the posterior belly of the digastric muscle. Objective To evaluate the consistency, accuracy, and safety of the landmark in identifying the facial nerve. Methods The study was designed in three steps: a cadaver study, a radiologic study, and a prospective clinical study. Anatomy was initially studied in two cadavers. Then the images of 200 temporal styloid regions were studied for consistency of the presence of the styloid base. In the second part of the radiologic study, the distance between the styloid base and the origin of the posterior belly of the digastric muscle was studied in 50 parotid regions. The clinical study involved 25 patients who underwent parotidectomy. Results The styloid base was present in all the images studied. The mean distance between the styloid base and the origin of the posterior belly of the digastric was found to be 0.72 cm (range: 0.45-0.99 cm). The facial nerve could be identified consistently and safely in all patients. Conclusion This trident landmark provided safe, accurate, and easy identification of the facial nerve using two fixed bony landmarks.