Optimization of glucose oxidase production by Aspergillus niger

The glucose oxidase was produced by fermentation using Aspergillus niger isolated from potato as producer organism and glucose as the carbon source (substrate). Maximum production of the enzyme (1.59 ìmoleHQMin-1ml-1) was achieved at 10% glucose concentration after 48 h of submerged fermentation. The pH for the optimal production of enzyme was found to be 5.5 (enzyme activity 1.56 ìmoleHQMin-1ml-1). Addition of urea (0.2%) and KH2PO4 (0.4%) into the fermentation medium increases enzyme activity (2.01 and 2.96 ìmoleHQMin-1ml-1, respectively) while MgSO4·7H2O was found to inhibit GOX production by A. niger.Key words: Glucose oxidase, Aspergillus niger, glucose oxidase

ASSESSEMENT OF ANTI-INFLAMMATORY AND ANTI-ARTHRITIS ACTIVITY OF JATROPHA GOSSYPIFOLIA IN RATS

Objectives: To investigate anti-inflammatory and anti-arthritic activity of latex Jatropha gossypifolia in rodents.Methods: The anti-inflammatory and anti-arthrit activity of latex from Jatropha gossypifolia (JGL) were tested in two different vivo models namely carrageenan induced paw edema in rats and Freund adjuvant arthritis. These models represent acute inflammatory condition and chronic inflammatory condition respectively.Results: The results of the present study showed that latex of JGL possessed remarkable anti-inflammatory activity in carrageenan induced edema (acute model) and antiarthritic activity in CFA induced (subchronic model) arthritis in rats. Conclusion: The latex of the plant Jatropha gossypifolia possesses anti-inflammatory and anti-arthritic activity might be due to its rich flavonoids content.Â

Safety, tumor trafficking and immunogenicity of chimeric antigen receptor (CAR)-T cells specific for TAG-72 in colorectal cancer.

BackgroundT cells engineered to express chimeric antigen receptors (CARs) have established efficacy in the treatment of B-cell malignancies, but their relevance in solid tumors remains undefined. Here we report results of the first human trials of CAR-T cells in the treatment of solid tumors performed in the 1990s.MethodsPatients with metastatic colorectal cancer (CRC) were treated in two phase 1 trials with first-generation retroviral transduced CAR-T cells targeting tumor-associated glycoprotein (TAG)-72 and including a CD3-zeta intracellular signaling domain (CART72 cells). In trial C-9701 and C-9702, CART72 cells were administered in escalating doses up to 1010 total cells; in trial C-9701 CART72 cells were administered by intravenous infusion. In trial C-9702, CART72 cells were administered via direct hepatic artery infusion in patients with colorectal liver metastases. In both trials, a brief course of interferon-alpha (IFN-α) was given with each CART72 infusion to upregulate expression of TAG-72.ResultsFourteen patients were enrolled in C-9701 and nine in C-9702. CART72 manufacturing success rate was 100% with an average transduction efficiency of 38%. Ten patients were treated in CC-9701 and 6 in CC-9702. Symptoms consistent with low-grade, cytokine release syndrome were observed in both trials without clear evidence of on target/off tumor toxicity. Detectable, but mostly short-term (≤14 weeks), persistence of CART72 cells was observed in blood; one patient had CART72 cells detectable at 48 weeks. Trafficking to tumor tissues was confirmed in a tumor biopsy from one of three patients. A subset of patients had 111Indium-labeled CART72 cells injected, and trafficking could be detected to liver, but T cells appeared largely excluded from large metastatic deposits. Tumor biomarkers carcinoembryonic antigen (CEA) and TAG-72 were measured in serum; there was a precipitous decline of TAG-72, but not CEA, in some patients due to induction of an interfering antibody to the TAG-72 binding domain of humanized CC49, reflecting an anti-CAR immune response. No radiologic tumor responses were observed.ConclusionThese findings demonstrate the relative safety of CART72 cells. The limited persistence supports the incorporation of co-stimulatory domains in the CAR design and the use of fully human CAR constructs to mitigate immunogenicity

HGS-ETR1, a fully human TRAIL-receptor 1 monoclonal antibody, induces cell death in multiple tumour types in vitro and in vivo

Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in a variety of tumour cells through activation of TRAIL-R1 and TRAIL-R2 death signalling receptors. Here, we describe the characterisation and activity of HGS-ETR1, the first fully human, agonistic TRAIL-R1 mAb that is being developed as an antitumour therapeutic agent. HGS-ETR1 showed specific binding to TRAIL-R1 receptor. HGS-ETR1 reduced the viability of multiple types of tumour cells in vitro, and induced activation of caspase 8, Bid, caspase 9, caspase 3, and cleavage of PARP, indicating activation of TRAIL-R1 alone was sufficient to induce both extrinsic and intrinsic apoptotic pathways. Treatment of cell lines in vitro with HGS-ETR1 enhanced the cytotoxicity of chemotherapeutic agents (camptothecin, cisplatin, carboplatin, or 5-fluorouracil) even in tumour cell lines that were not sensitive to HGS-ETR1 alone. In vivo administration of HGS-ETR1 resulted in rapid tumour regression or repression of tumour growth in pre-established colon, non-small-cell lung, and renal tumours in xenograft models. Combination of HGS-ETR1 with chemotherapeutic agents (topotecan, 5-fluorouracil, and irinotecan) in three independent colon cancer xenograft models resulted in an enhanced antitumour efficacy compared to either agent alone. Pharmacokinetic studies in the mouse following intravenous injection showed that HGS-ETR1 serum concentrations were biphasic with a terminal half-life of 6.9–8.7 days and a steady-state volume of distribution of approximately 60 ml kg−1. Clearance was 3.6–5.7 ml−1 day−1 kg−1. These data suggest that HGS-ETR1 is a specific and potent antitumour agent with favourable pharmacokinetic characteristics and the potential to provide therapeutic benefit for a broad range of human malignancies

Gamma probes and their use in tumor detection in colorectal cancer

The purpose of this article is to summarize the role of gamma probes in intraoperative tumor detection in patients with colorectal cancer (CRC), as well as provide basic information about the physical and practical characteristics of the gamma probes, and the radiopharmaceuticals used in gamma probe tumor detection. In a significant portion of these studies, radiolabeled monoclonal antibodies (Mabs), particularly 125I labeled B72.3 Mab that binds to the TAG-72 antigen, have been used to target tumor. Studies have reported that intraoperative gamma probe radioimmunodetection helps surgeons to localize primary tumor, clearly delineate its resection margins and provide immediate intraoperative staging. Studies also have emphasized the value of intraoperative gamma probe radioimmunodetection in defining the extent of tumor recurrence and finding sub-clinical occult tumors which would assure the surgeons that they have completely removed the tumor burden. However, intraoperative gamma probe radioimmunodetection has not been widely adapted among surgeons because of some constraints associated with this technique. The main difficulty with this technique is the long period of waiting time between Mab injection and surgery. The technique is also laborious and costly. In recent years, Fluorine-18-2-fluoro-2-deoxy-D-glucose (18F-FDG) use in gamma probe tumor detection surgery has renewed interest among surgeons. Preliminary studies during surgery have demonstrated that use of FDG in gamma probe tumor detection during surgery is feasible and useful

A comprehensive overview of radioguided surgery using gamma detection probe technology

The concept of radioguided surgery, which was first developed some 60 years ago, involves the use of a radiation detection probe system for the intraoperative detection of radionuclides. The use of gamma detection probe technology in radioguided surgery has tremendously expanded and has evolved into what is now considered an established discipline within the practice of surgery, revolutionizing the surgical management of many malignancies, including breast cancer, melanoma, and colorectal cancer, as well as the surgical management of parathyroid disease. The impact of radioguided surgery on the surgical management of cancer patients includes providing vital and real-time information to the surgeon regarding the location and extent of disease, as well as regarding the assessment of surgical resection margins. Additionally, it has allowed the surgeon to minimize the surgical invasiveness of many diagnostic and therapeutic procedures, while still maintaining maximum benefit to the cancer patient. In the current review, we have attempted to comprehensively evaluate the history, technical aspects, and clinical applications of radioguided surgery using gamma detection probe technology

DataSet of the First Iteration of studying Wadi Hanifah's Place-Image and -Identity After the Rehabilitation

The survey producing this data was used for a study that aimed to examine the impacts of a large-scale rehabilitation project of an urban ecosystem, particularly in terms of its place-image and place-identity. The selected case-study was that of Wadi Hanifah, a valley located in Riyadh, Saudi Arabia. The questions aimed to examine the perceptions, uses, popularity, and attachment through the meanings and perceptions people tie to it, through the physical environment, and through the activities people par-take in at the Wadi. The data also provides basic information of age, gender, nationality, and residency

DataSet of the First Iteration of studying Wadi Hanifah's Place-Image and -Identity After the Rehabilitation

The survey producing this data was used for a study that aimed to examine the impacts of a large-scale rehabilitation project of an urban ecosystem, particularly in terms of its place-image and place-identity. The selected case-study was that of Wadi Hanifah, a valley located in Riyadh, Saudi Arabia. The questions aimed to examine the perceptions, uses, popularity, and attachment through the meanings and perceptions people tie to it, through the physical environment, and through the activities people par-take in at the Wadi. The data also provides basic information of age, gender, nationality, and residency.THIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV