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Silk Reservoirs for Local Delivery of Cisplatin for Neuroblastoma Treatment: In Vitro and In Vivo Evaluations

Yavuz, Burcin; Zeki, Jasmine; Taylor, Jordan; Harrington, Kristin; Coburn, Jeannine M; Ikegaki, Naohiko; Kaplan, David L; Chiu, Bill
Neuroblastoma is the most common extracranial childhood tumor, and current treatment requires surgical resection and multidrug chemotherapy. Local, perioperative delivery of chemotherapeutics is a promising treatment method for solid tumors that require surgical removal. In this study, we have aimed to develop a controlled-release implant system to deliver cisplatin in tumor or tumor resection area. Silk fibroin, a biodegradable, nonimmunogenic biopolymer was used to encapsulate different doses of cisplatin in a reservoir system. The physical integrity of the reservoirs was characterized by evaluating the crystalline structure of silk secondary structure using FTIR spectroscopy. The in vitro release of cisplatin was evaluated in phosphate-buffered saline at 37°C, and the reservoirs were able to release the drug up to 30 days. The cytotoxicity of cisplatin and cisplatin reservoirs were tested on KELLY cells. Cytotoxicity data showed 3.2 μg/mL cisplatin was required to kill 50% of the cell population, and the released cisplatin from the silk reservoirs showed significant cytotoxicity up to 21 days. Intratumoral implantation of silk reservoirs into an orthotopic neuroblastoma mouse model decreased tumor growth significantly when compared with control subjects. These results suggest that silk reservoirs are promising carriers for cisplatin delivery to the tumor site.
PMCID:6640112
PMID: 30905702
ISSN: 1520-6017
CID: 5604032

Disseminated injection of vincristine-loaded silk gel improves the suppression of neuroblastoma tumor growth

Zeki, Jasmine; Taylor, Jordan S; Yavuz, Burcin; Coburn, Jeannine; Ikegaki, Naohiko; Kaplan, David L; Chiu, Bill
BACKGROUND:Advanced-stage neuroblastoma patients require multiagent chemotherapy. Intratumoral implantation of vincristine-loaded silk gel uses local diffusion to decrease orthotopic neuroblastoma tumor growth in mice. We hypothesize that injecting vincristine-loaded silk gel into 8 locations within the tumor, instead of only centrally, decreases the diffusion distance and improves tumor growth suppression. METHODS:and histologic examination. RESULTS:over 3 days. The time to inflection point was 6.6 days for central, 13.3 days for 8-point injection (P < .05). Using the sphere volume equation to approximate tumor volume, splitting the volume into 1/8 decreased the diffusion radius by 1/2. Histologic examination confirmed tumor necrosis adjacent to vincristine-loaded silk gel. CONCLUSION:Injecting vincristine-loaded sustained release silk gel at 8 separate locations halved the diffusion distance and doubled the time for the tumor to reach the growth inflexion point.
PMCID:6153071
PMID: 30061039
ISSN: 1532-7361
CID: 5604112

Endoscopic Excision of Benign Facial Masses in Children: A Review of Outcomes

Foster, Deshka; Sinclair, Tiffany J; Taylor, Jordan S; Dutta, Sanjeev; Lorenz, Hermann P; Bruzoni, Matias
PURPOSE/OBJECTIVE:Benign masses of the eyebrow and forehead are common in pediatric patients and can result in facial asymmetry, discomfort, or super-infection. Excision is classically conducted via an incision directly over the mass, which can produce sub-optimal cosmesis. Recently, an endoscopic approach using pediatric brow-lift equipment has been adopted. We reviewed our center's experience with endoscopic removal of benign facial lesions and compared these cases with an equivalent series of open cases. MATERIALS AND METHODS/METHODS:A retrospective chart review was conducted to identify pediatric cases of endoscopic and open removal of benign eyebrow or forehead lesions at our institution from 2009 to 2016. Clinical and cosmetic outcomes were reviewed. RESULTS:A total of 40 endoscopic and 25 open cases of excision of benign facial lesions in children were identified. For the patients who underwent endoscopic excision, the majority (85%) presented with a cyst located at the eyebrow. Histologic examination revealed 36 dermoid cysts (90%), 2 epidermal cysts, and 2 pilomatrixomas. Of the 36 cases with post-operative follow-up, 32 patients (89%) had an uncomplicated recovery with good cosmesis. Two patients had an eyebrow droop that resolved without intervention. One patient had localized numbness overlying the site, but no motor deficits. One patient presented with a recurrent dermoid cyst that required open resection. For the patients who underwent open excision, the majority (52%) had dermoid cysts located at the eyebrow. Of the 22 cases with follow-up, 20 of the patients had an uncomplicated recovery (90%). Comparing the rate of complications, there was no statistically significant difference between the two groups (P = 1.0). CONCLUSION/CONCLUSIONS:Endoscopic excision of benign forehead and eyebrow lesions in pediatric patients is feasible and yields excellent cosmetic results. When compared with open excision, complication rates are similar between both approaches and a facial scar can be avoided with an endoscopic approach.
PMID: 29446701
ISSN: 1557-9034
CID: 5603902

Dilation of Esophageal Stricture in a Pediatric Patient Using Functional Lumen Imaging Probe Technology Without the Use of Fluoroscopy [Case Report]

Taylor, Jordan S; Danzer, Enrico; Berquist, William E; Wall, James K
PMID: 29470294
ISSN: 1536-4801
CID: 5603922

Combined application of Indocyanine green (ICG) and laser lead to targeted tumor cell destruction

Taylor, Jordan S; Zeki, Jasmine; Ikegaki, Naohiko; Chen, Liaohai L; Chiu, Bill
PURPOSE/OBJECTIVE:Precise excision of neuroblastoma is challenging, especially when tumors adhere to vital structures. Indocyanine green (ICG), an FDA-approved dye with absorption peaking at 800 nm, can absorb the near IR laser energy and release heat in the dyed tissue. We hypothesize that by injecting ICG at tumor sites followed by precise laser application, tumor cell death can be selectively targeted. METHODS:Orthotopic neuroblastoma tumors were created in the adrenal gland of immunocompromised mice. Tumor, liver, kidney, and muscle tissues were chosen for ICG injection. Intervention variables included presence of tumor capsule, continuous vs. pulsed laser treatment and total energy delivered. Control groups included laser or ICG only. Tissues were stained with hematoxylin/eosin. RESULTS:Continuous wave laser generated excessive heat, causing damage in all tissues. When using pulsed laser treatment, liver, kidney, muscle, and intact tumor tissues showed no cell death when treated with laser alone or laser plus ICG. Tumor tissue with the capsule removed, however, showed cell death on histology. CONCLUSIONS:Pulsed laser treatment combined with ICG causes targeted tumor cell death in neuroblastoma tumor without capsule. No cell death was observed when tumor capsule was present, when only laser was used, or when applied over non-tumor tissues.
PMCID:9020883
PMID: 30244940
ISSN: 1531-5037
CID: 5603962

Impact of societal factors and health care delivery systems on gastroschisis outcomes

Taylor, Jordan S; Shew, Stephen B
Care of infants with gastroschisis is associated with a significant burden on health care delivery systems. Mortality rates in patients with gastroschisis have significantly improved over the past few decades. However, the condition is still associated with significant short-term and potentially long-term morbidity. Significant variations in clinical outcomes and resource utilization may be explained by several factors including provider and hospital experience, level of neonatal intensive care, variations in hospital regionalization of care, and differences in healthcare delivery systems. Reviewing and assessing these hospital and healthcare system related factors are paramount in addressing variations in gastroschisis care and improving outcomes for these vulnerable infants.
PMID: 30413263
ISSN: 1532-9453
CID: 5603992