Oncofetal Chondroitin Sulfate Is a Highly Expressed Therapeutic Target in Non-Small Cell Lung Cancer.

Broad-spectrum therapeutics in non-small cell lung cancer (NSCLC) are in demand. Most human solid tumors express proteoglycans modified with distinct oncofetal chondroitin sulfate (CS) chains that can be detected and targeted with recombinant VAR2CSA (rVAR2) proteins and rVAR2-derived therapeutics. Here, we investigated expression and targetability of oncofetal CS expression in human NSCLC.

In Vivo Delivery of a DNA-Encoded Monoclonal Antibody Protects Non-human Primates against Zika Virus.

Zika virus (ZIKV) infection is endemic to several world regions, and many others are at high risk for seasonal outbreaks. Synthetic DNA-encoded monoclonal antibody (DMAb) is an approach that enables in vivo delivery of highly potent mAbs to control infections. We engineered DMAb-ZK190, encoding the mAb ZK190 neutralizing antibody, which targets the ZIKV E protein DIII domain.

Adapting the Ideas of Translational Science for Translational Family Science.

Family science has been doing translational science since before it came into vogue. Nevertheless, the field has been subjected to the same forces in the broader academy that have created a widening chasm between discovery and practice. Thus, the primary objective of this article is to translate the principles, concepts, and models of translational science to solidify an identity for family science and help the field move forward in broader academic, care delivery, and policy arenas.

Relevance of platinum-sensitivity status in relapsed/refractory extensive-stage small-cell lung cancer in the modern era: a patient-level analysis of southwest oncology group trials.

Background: Extensive-stage small-cell lung cancer (SCLC) patients who progress after platinum-based chemotherapy are traditionally categorized as platinum sensitive (progression ≥ 90 days from last platinum dose) or refractory (progression < 90 days), a practice arising from seminal observations of worse survival in refractory patients. Subsequent trials accounted for platinum sensitivity, resulting in higher sample sizes and increased resource use.

Methods: To assess whether platinum-sensitivity status remains associated with outcomes, patient-level data from recent Southwest Oncology Group trials in second- and/or third-line extensive-stage SCLC were pooled.

Southwest Oncology Group S0802: a randomized, phase II trial of weekly topotecan with and without ziv-aflibercept in patients with platinum-treated small-cell lung cancer.

Purpose: Development of new therapies for previously treated small-cell lung cancer (SCLC) is a major unmet need. Here, we describe a randomized, phase II trial of weekly topotecan with or without ziv-aflibercept (VEGF-trap) in this clinical setting.

Patients And Methods: Patients with previously treated SCLC (one line of platinum-based chemotherapy), performance status of 0 to 1, adequate organ function, treated brain metastases, and no recent vascular events or bleeding diatheses were eligible.

FN14 expression correlates with MET in NSCLC and promotes MET-driven cell invasion.

The five-year survival rate in advanced non-small cell lung cancer (NSCLC) remains below ten percent. The invasive and metastatic nature of NSCLC tumor cells contributes to the high mortality rate, and as such the mechanisms that govern NSCLC metastasis is an active area of investigation. Two surface receptors that influence NSCLC invasion and metastasis are the hepatocyte growth factor receptor (HGFR/MET) and fibroblast growth factor-inducible 14 (FN14).

Objective review of mediastinal lymph node examination in a lung cancer resection cohort.

Background: Accurate staging of resected lung cancer requires mediastinal lymph node (MLN) examination. MLN dissection (MLND) and systematic sampling (SS) are acceptable procedures; random sampling (RS) and no sampling (NS) are not. Forty percent of US lung cancer resections have NS.

Pathologic lymph node staging practice and stage-predicted survival after resection of lung cancer.

Background: Lymph node status is the most important prognostic factor in resectable nonsmall-cell lung cancer (NSCLC). We examined the relationship between the pattern of lymph node examination (including the number and anatomic location of resected lymph nodes), pathologic nodal stage, and survival after NSCLC resection.

Methods: Retrospective review of all NSCLC resections in the Memphis Metropolitan Area from January 1, 2004, to December 31, 2007.

Quality of surgical resection for nonsmall cell lung cancer in a US metropolitan area.

Background: Curative treatment of early stage nonsmall cell lung cancer (NSCLC) requires good quality surgical resection (GQR). The degree of compliance with national recommendations for GQR is poorly defined. We sought to quantitatively define the degree of compliance in a consecutive series of NSCLC resections.

Epidermal growth factor receptor polymorphisms and risk for toxicity in paediatric patients treated with gefitinib.

Purpose: To investigate associations between germline genetic variations in the epidermal growth factor receptor (EGFR) and toxicity in paediatric patients treated with gefitinib.

Patients And Methods: Gefitinib treatment and toxicity data from five paediatric clinical trials were combined. EGFR genotypes evaluated included -191C>A, -216G>T, Arg497Lys and intron 1 CA sequence repeat number.

Outcome of surgical resection for pathologic N0 and Nx non-small cell lung cancer.

Purpose: Metastasis to lymph nodes (LNs) connotes poor prognosis in non-small cell lung cancer (NSCLC). Sufficient LNs must be examined to accurately determine LN negativity. Patients with no LNs examined (pNx) have an indeterminate stage, may have undetected disease and erroneous assignment to a low-risk group.

Complications of bariatric surgery: implications for the covering physician.

Bariatric surgery is the only effective option for sustained weight loss for morbidly obese patients. The increasing prevalence of obesity in America and the application of a laparoscopic approach to bariatric surgery have combined to dramatically increase the number of patients undergoing these types of operations. The number of bariatric surgeons and centers devoted to surgery of the morbidly obese is also rising.

An assessment of the antinociceptive efficacy of intrathecal and epidural contulakin-G in rats and dogs.

Contulakin-G is a novel conopeptide with an incompletely defined mechanism of action. To assess nociceptive activity we delivered Contulakin-G as a bolus intrathecally (0.03, 0.

Opiate pharmacology of intrathecal granulomas.

Background: Chronic intrathecal morphine infusion produces intradural granulomas. The authors examined a variety of opioids infused intrathecal for analgesic activity and toxicity.

Methods: Two sets of experiments were undertaken in dogs with chronic intrathecal catheters: (1) Six-hour intrathecal infusions were used to determine the full analgesic dose and the maximum tolerated dose.

Time course and role of morphine dose and concentration in intrathecal granuloma formation in dogs: a combined magnetic resonance imaging and histopathology investigation.

Background: Intrathecal morphine infusion leads to intrathecal granulomas. In dogs, the authors examined time course of granuloma formation and the role of concentration in granuloma development.

Methods: Dogs were prepared with lumbar intrathecal catheters and vest-mounted pumps.

Safety evaluation of intrathecal substance P-saporin, a targeted neurotoxin, in dogs.

Intrathecal (IT) substance P-Saporin (SP-SAP), a 33-kDa-targeted neurotoxin, produces selective destruction of superficial neurokinin 1 receptor (NK1r)-bearing cells in the spinal dorsal horn. In rats, SP-SAP prevents the formation of hyperalgesia and can reverse established neuropathic pain behavior in rodents. To determine the safety of this therapeutic modality in a large animal model, beagles received bolus IT lumbar injections of vehicle, SP-SAP (1.

Further results of incorporating innovative procedures in a surgical residency.

The instruction in precipitously advancing surgical technologies remains a real challenge to every surgery program. Our institution's ongoing experience with an identified center for student and resident education and clinical investigation provides an option for addressing these needs in a general surgery residency. Over the past 8 years, we have developed and described previously the Center for Advanced Surgical Technologies (CAST) in a joint undertaking of the Department of Surgery and the Norton Hospital, an affiliated hospital on our medical school campus.

The use of intrathecal midazolam in humans: a case study of process.

Unlabelled: Early preclinical work demonstrated the potential role of spinal benzodiazepine pharmacology in regulating spinal nociceptive transmission. We review this preclinical activity and the evolving implementation of intrathecal midazolam in humans for pain management. Important elements in this development for use in humans are issues pertinent to safety and the preclinical reports that have increased our understanding of intrathecal midazolam toxicity.

Tissue injury models of persistent nociception in rats.

The purpose of this chapter is to provide guidance to the novice investigator as to two models of ongoing nociception in rats. The models described herein are the formalin test, in which an irritant is injected subcutaneously into a dorsal paw and the numbers of flinches produced over 60 min are counted, and a mild burn model that produces a transitory primary and secondary thermal and mechanical hyperalgesia lasting approx 90 min. These models allow assessment of spinal sensitization, which may be an important factor when considering plasticity associated with human pain states.

Assessment of acute thermal nociception in laboratory animals.

Models of acute nociception using a thermal stimulus are widely employed as screening methods for nociceptive properties of new drug compounds. In this chapter, detailed descriptions for conducting of two of the most commonly used models; the hot plate test and the "Hargreaves test," are described. These models are applicable to both rats and mice and have the advantage of allowing repeated and multiple testing using a single animal because the stimulus is transitory and produces no tissue damage.

Chronically infused intrathecal morphine in dogs.

Background: Despite the extensive use of intrathecal morphine infusion for pain, no systematic safety studies exist on its effects in high concentrations. The authors assessed the effects of morphine and clonidine given 28 days intrathecally in dogs.

Methods: Beagles with lumbar intrathecal catheters received solutions delivered by a vest-mounted infusion pump.

The consequences of methylmercury exposure on interactive functions between astrocytes and neurons.

Methylmercury (MeHg) is a highly neurotoxic, environmentally ubiquitous chemical that exerts its toxic effects by largely unknown mechanisms. Maintenance of optimal intracellular concentrations of glutathione (GSH) is vital for cellular defenses against damage from free radicals. Since astrocytes play an essential role in providing GSH precursors to neurons, studies were directed at the effect of MeHg on cystine transport in both cell types.