Regulation of Genetically Engineered Food Products: A Market-Oriented Perspective

Only twenty years after the landmark Asilomar meeting where scientists discussed the opportunities and possible risks presented by the ability to transfer DNA from one organism to another,' bioengineered products have moved outside the confines of the laboratory into commercial uses in the pharmaceutical and food-processing industries. Recent advances in molecular biology and the application of new technologies to the production of food have opened the door to a new world of bioengineered food. Agricultural biotechnology has the potential to "meet the needs of a rapidly growing population and minimize the toxic influences of traditional farming practices on the environment." Furthermore, it promises to improve human nutritional intake and can even aim to satisfy our desire for novel or exotic foods with aesthetically appealing textures, appearances and tastes. At the same time, however, the public remains suspicious of the uses to which genetic engineering may be put, as well as somewhat wary of the foods derived from genetically engineered organisms. Critics of the new technology have long argued that recombinant DNA techniques and products derived from them pose significant and ill-understood risks to human health and safety) Against this backdrop, the federal Food and Drug Administration ("FDA") has sought to fulfill its statutory mission to protect the safety and wholesomeness of the food supply) Because the FDA has chosen to address the novel issues raised by the application of biotechnology to food through existing statutory authority, manufacturers and producers of bioengineered food, as well as others concerned with the availability of safe, nutritious and inexpensive food, have sought clarification from the FDA about how these decades-old standards will be applied. In the near-term future at least, the FDA'S response, published in l992, appears likely to direct commercial efforts at bioengineered foods into channels that may not realize the full benefits of biotechnology, both from consumerist and marketing perspectives, as quickly and efficiently as possible

Acupuncture Treatment for Bortezomib-Induced Peripheral Neuropathy: A Case Report

Peripheral neuropathy is a common and severe dose-limiting side effect of the chemotherapy agent, bortezomib, in multiple myeloma patients. Treatment with narcotics, antidepressants, and anticonvulsants has limited response and potential significant side effects. Acupuncture has been reported to be effective in treating diabetic neuropathy and chemo-induced peripheral neuropathy. There has not been report on the effect of acupuncture in treating bortezomib-induced peripheral neuropathy specifically. Here, we report a successful case of using acupuncture to relieve bortezomib-induced peripheral neuropathy symptoms

A tumor growth inhibition model based on M-protein levels in subjects with relapsed/refractory multiple myeloma following single-agent carfilzomib use

Change in tumor size estimated using longitudinal tumor growth inhibition (TGI) modeling is an early predictive biomarker of clinical outcomes for multiple cancer types. We present the application of TGI modeling for subjects with multiple myeloma (MM). Longitudinal time course changes in M‐protein data from relapsed and/or refractory MM subjects who received single‐agent carfilzomib in phase II studies (n = 456) were fit to a TGI model. The tumor growth rate estimate was similar to that of other anti‐myeloma agents, indicating that the model is robust and treatment‐independent. An overall survival model was subsequently developed, which showed that early change in tumor size (ECTS) at week 4, Eastern Cooperative Oncology Group performance status (ECOG PS), hemoglobin, sex, percent bone marrow cell involvement, and number of prior regimens were significant independent predictors for overall survival (P < 0.001). ECTS based on M‐protein modeling could be an early biomarker for survival in MM following exposure to single‐agent carfilzomib

Pharmacokinetics and safety of elotuzumab combined with lenalidomide and dexamethasone in patients with multiple myeloma and various levels of renal impairment: Results of a phase Ib study

AbstractIntroductionThe present study evaluated the pharmacokinetics and safety of elotuzumab, a humanized IgG1 monoclonal antibody against signaling lymphocyte activation molecule-F7, combined with lenalidomide and dexamethasone, in patients with multiple myeloma (MM) and renal impairment.Patients and MethodsPatients with MM and normal renal function (NRF) (creatinine clearance [CrCl] ≥ 90 mL/min), severe renal impairment (SRI) (CrCl < 30 mL/min, not requiring dialysis), or end-stage renal disease (ESRD) (requiring dialysis) were enrolled in this open-label, phase Ib study. Elotuzumab (10 mg/kg), lenalidomide (5-25 mg), and dexamethasone (40 mg) were administered in 28-day cycles until disease progression or unacceptable toxicity developed. The primary endpoint was single-dose elotuzumab pharmacokinetics.ResultsA total of 26 patients (median age, 63 years) were treated (NRF, n = 8; SRI, n = 9; ESRD, n = 9). The median baseline CrCl was 105 mL/min (range, 84-146 mL/min) for those with NRF and 26 mL/min (range, 15-33 mL/min) for those with SRI. Twenty-three patients (89%) had received previous therapy (median, 2 regimens; range, 1-7). Treatment was discontinued in 6 patients with NRF, 4 with SRI, and 5 with ESRD, primarily because of disease progression. The mean elotuzumab serum concentrations were comparable across groups (n = 23). No statistically significant differences were observed in the maximum observed serum concentration, area under the concentration–time curve from time 0 to the last quantifiable serum concentration, or area under the concentration–time curve from time 0 to infinity when the SRI and ESRD groups were compared with the NRF group (P > .05). All patients had ≥ 1 adverse event (AE). Of the 8 patients with NRF, 9 with SRI, and 9 with ESRD, 7, 8, and 7 experienced grade 3 to 4 AEs. The overall response rates were 75% in the NRF, 67% in the SRI, and 56% in the ESRD groups.ConclusionThe results of the present study support the use of elotuzumab for the treatment of patients with MM and renal dysfunction without dose adjustment

Landslide investigation using Electrical Resistivity Imaging (ERI) method at Kg. Chuchoh Puteri, Kuala Krai, Kelantan, Malaysia

The possible landslide in Kg. Chuchoh Puteri, Kuala Krai, Kelantan were investigated using the electrical resistivity imaging (ERI) technique. The survey for the collecting of data was conducted along six lines. Each survey line was 200 meters long, with 5 meters between electrodes. ABEM Terrameter LS 1 is used to record all the data and RES2DINV software is used to process it. While conducting the geophysical survey, the relationship between resistivity and conductivity is reciprocal. A pole-dipole array configuration was utilised in survey Lines 1, 2, 4 and 5 and in survey Lines 3 and 6, a Schlumberger array configuration. Survey Lines 2, 3, and 6 are primarily indicated as having a high probability of experiencing a landslide using the pseudosection 2-D profile. The findings reveal varying resistivity at a depth of study between 40 and 80 meters for a survey line length of 200 meters. In general, the resistivity survey's seven pseudosections showed two distinct types of soils: dry residual soil (1–1500 Ωm) and weathered volcanic rocks (>1500 Ωm). Residual soils with varying saturation levels, hard soil and weathered volcanic rock, have dominated the soil profile. These profiles can generally be divided into two (2) zones: thin/thick layers of loose to dense residual soils (10–100 Ωm; Zone A) and thin/thick layers of dense and hard material (> 1000 Ωm)

Increased Prevalence of Bisphosphonate-Related Osteonecrosis of the Jaw with Vitamin D Deficiency in Rats

Necrotic bone exposure in the oral cavity has recently been reported in patients treated with nitrogen-containing bisphosphonates as part of their therapeutic regimen for multiple myeloma or metastatic cancers to bone. It has been postulated that systemic conditions associated with cancer patients combined with tooth extraction may increase the risk of osteonecrosis of the jaw (ONJ). The objective of this study was to establish an animal model of bisphosphonate-related ONJ by testing the combination of these risk factors. The generation of ONJ lesions in rats resembling human disease was achieved under the confluence of intravenous injection of zoledronate (ZOL; 35 µg/kg every 2 weeks), maxillary molar extraction, and vitamin D deficiency [VitD(−)]. The prevalence of ONJ in the VitD(−)/ZOL group was 66.7%, which was significantly higher (p < .05, Fisher exact test) than the control (0%), VitD(−) (0%), and ZOL alone (14.3%) groups. Similar to human patients, rat ONJ lesions prolonged the oral exposure of necrotic bone sequestra and were uniquely associated with pseudoepitheliomatous hyperplasia. The number of terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate–biotin nick-end label–positive (TUNEL+) osteoclasts significantly increased on the surface of post–tooth extraction alveolar bone of the VitD(−)/ZOL group, where sustained inflammation was depicted by [18F]fluorodeoxyglucose micro-positron emission tomography (µPET). ONJ lesions were found to be associated with dense accumulation of mixed inflammatory/immune cells. These cells, composed of neutrophils and lymphocytes, appeared to juxtapose apoptotic osteoclasts. It is suggested that the pathophysiologic mechanism(s) underpinning ONJ may involve the interaction between bisphosphonates and compromised vitamin D functions in the realm of skeletal homeostasis and innate immunity. © 2010 American Society for Bone and Mineral Research

Primary plasma cell leukemia: consensus definition by the International Myeloma Working Group according to peripheral blood plasma cell percentage

Primary plasma cell leukemia (PCL) has a consistently ominous prognosis, even after progress in the last decades. PCL deserves a prompt identification to start the most effective treatment for this ultra-high-risk disease. The aim of this position paper is to revisit the diagnosis of PCL according to the presence of circulating plasma cells in patients otherwise meeting diagnostic criteria of multiple myeloma. We could identify two retrospective series where the question about what number of circulating plasma cells in peripheral blood should be used for defining PCL. The presence of ?5% circulating plasma cells in patients with MM had a similar adverse prognostic impact as the previously defined PCL. Therefore, PCL should be defined by the presence of 5% or more circulating plasma cells in peripheral blood smears in patients otherwise diagnosed with symptomatic multiple myeloma.Funding: This work has been supported in part by grants from the Instituto de Salud Carlos III, Spanish Ministry of Health (FIS PI19/00669), Fondo Europeo de Desarrollo Regional (FEDER) and 2017SGR00792 (AGAUR; Generalitat de Catalunya)

A Phase II Trial of AZD6244 (Selumetinib, ARRY-142886), an Oral MEK1/2 Inhibitor, in Relapsed/Refractory Multiple Myeloma

AZD6244 is a MEK1/2 inhibitor with significant preclinical activity in multiple myeloma (MM) cells. This phase 2 study used a two-stage Simon design to determine the AZD6244 response rate in patients with relapsed or refractory MM