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Objective(s): Miltuximab® is a chimeric antibody targeting Glypican-1 (GPC-1), a cell surface antigen which is overexpressed in solid cancers. Miltuximab® has shown promising safety and efficacy in radioimmunotherapy models of prostate cancer. This first in human study used Miltuximab® radiolabelled with Gallium-67 ([67Ga]Ga-DOTA-Miltuximab®). The primary study endpoint was to establish safety and tolerability of Miltuximab®. Secondary endpoints were biodistribution, tumour targeting and pharmacokinetic analysis.Methods: Four cohorts of three patients (9 with advanced prostate cancer, 2 with pancreatic and 1 with bladder cancer) were dosed with 1 mg, ~250 MBq of [67Ga]Ga-DOTA-Miltuximab®. Cohort 1 received [67Ga]Ga-DOTA-Miltuximab® alone, while cohorts 2-4 were pre-infused with increasing doses (3.5, 11.5 and 24 mg, respectively) of unlabelled Miltuximab®-DOTA 1 hour prior to [67Ga]Ga-DOTA-Miltuximab®. Safety and tolerability were assessed by clinical and standard laboratory assessments. Patients underwent whole body gamma-camera scans and SPECT/CT scans up to 144 h post-infusion. Total organ radiation exposure was determined by dosimetry of whole-body gamma scans.Results: The dosing regimen was well tolerated, with no drug-related adverse events observed. Liver and spleen uptake of [67Ga]Ga-DOTA-Miltuximab® was observed. Liver uptake was reduced by pre-infusion of unlabelled Miltuximab®-DOTA. Dosimetry analysis showed a favorable exposure profile. [67Ga]Ga-DOTA-Miltuximab® targeting to tumour sites was observed in two prostate cancer patients who had failed enzalutamide treatment. Higher doses of unlabelled antibody achieved lower liver uptake and increased antibody serum half life.Conclusions: This study is the first in human for Miltuximab® a first in class antibody targeting GPC-1. The trial met its primary endpoint of safety, demonstrating its potential as a safe and tolerable monoclonal antibody. This safety data, together with targeting to tumour lesions and biodistribution information supports the further clinical development of Miltuximab® as a theranostic agent in a planned Phase I human trial.Trial registration: ANZCTR, ACTRN12616000787482, https://www.anzctr.org.

Background. When asked about employees' political behavior in the workplace, they often see it as signs of good behavior and see it as an ugly act that achieves personal goals at the expense of others, and May be harmful to the goals of the organization or individuals. Objectives. This study aimed to test a model of factors affecting political behavior in the sports industry. In the study, other objectives such as the moderating role of political skills and will, as well as the mediating role of the perception of organizational politics are discussed. Methods. The sample size of the present research is 705 people which are employees of the Ministry of Sport and federations (of football, volleyball, handball, basketball, weight-lifting, wrestling, taekwondo, veterans and disabled). These were selected by simple random sampling and a questionnaire was used to evaluate the variables under study. Results. The results did not show significant direct relationship between inter-organizational factors and show that perception of organizational politics mediated the relationship between inter-organizational factors and political behavior. The results showed that political skills and will, played the role of the moderator of organizational factors with political behavior. Conclusion. Politics is a fact of life in the organizations. Those who are not able to observe their political behavior cannot understand the fact that organization is a political system. Thus, the organizations should lead to the politicization and managers should make necessary attempts towards reaching organizational goals which is important.

Today’s fast-growing demands at the global level for mobile applications (apps) cause customers to call for the customization of their apps to fit their individualized needs and business realms. Customization is a challenge for apps-development companies when they want to satisfy their numerous users in a crowded competitive market. Moreover, pursuing customization involves additional challenges when ramping up app development projects in order to meet demands at a larger scale. To address this challenge, we proposed a framework to systematize and support mobile apps’ development consistently with a customer-driven approach and modular design philosophy. From a practical point of view, the proposed framework integrates quality function deployment (QFD), axiomatic design (AD) principles, and practices from the ITIL (Information Technology Infrastructure Library) framework. The framework supports a systematic process for translating customer needs into design parameters as well as supporting prioritization of ITIL practices for further development. The effectiveness of the framework was explored in practice through a case study about an app supporting relief in the 2020 COVID-19 pandemic, as well as a survey among potential users. The assessment of the framework indicated an average score ranging between 3.58 and 3.92 in a five-point Likert scale for all of the items used in the survey.

Harvesting practices of potato is one of the most difficult, troublesome and sensitive stages. Potatoes enter the machine with huge amounts of clod and stones: In the meantime separation of potato some stone and clod, which are the same size as of that the potatoes, shall be confide red a major problem. Many methods of study by investigators are based on physical properties of potato, stone and clod. In the present research with regards to the farm conditions and economic situation of the Iranian farmers, the beveled conveyor method is recommended. In this method, primarily a schematic design of the separating section of the stones and clod and the crop was produced and important parameters such as the surface angle, conveyor-belt motion speed and type of the conveyor, which play a key role in the separation stage, were studied. The test was carried out on the factorial basis and complete random block, using 3 angles factors in 5 levels (5,10,15.17.5 and 20 degrees) and the speed on 5 levels (100,200,300,400 and 600 RPM) and the belt type with 2 surfaces (soft and rough) repeated 5 times. The SPSS software was used to analyze data. The result revealed that the ideal combination of the angle, speed and belt type for acquiring the highest separation rate and the least amount of mix clod, stones of the separated potatoes are the order, and the crop would be the angle 15 degrees, the speed of 300 RPM, with the use of soft belt, and the angle of 17.5 degrees and the speed of 200 RPM is recommended for a rough belt.

Objectives: Miltuximab ® is a chimeric antibody targeting Glypican-1 (GPC-1), a cell surface antigen which is overexpressed in solid cancers. Miltuximab ® has shown promising safety and efficacy in radioimmunotherapy models of prostate cancer. This first in human study used Miltuximab ® radiolabelled with Gallium-67 ([ 67 Ga]Ga-DOTA-Miltuximab ® ). The primary study endpoint was to establish safety and tolerability of Miltuximab ® . Secondary endpoints were biodistribution, tumour targeting and pharmacokinetic analysis., Methods: Four cohorts of three patients (9 with advanced prostate cancer, 2 with pancreatic and 1 with bladder cancer) were dosed with 1 mg, ~250 MBq of [ 67 Ga]Ga-DOTA-Miltuximab ® . Cohort 1 received [ 67 Ga]Ga-DOTA-Miltuximab ® alone, while cohorts 2-4 were pre-infused with increasing doses (3.5, 11.5 and 24 mg, respectively) of unlabelled Miltuximab ® -DOTA 1 hour prior to [ 67 Ga]Ga-DOTA-Miltuximab ® . Safety and tolerability were assessed by clinical and standard laboratory assessments. Patients underwent whole body gamma-camera scans and SPECT/CT scans up to 144 h post-infusion. Total organ radiation exposure was determined by dosimetry of whole-body gamma scans., Results: The dosing regimen was well tolerated, with no drug-related adverse events observed. Liver and spleen uptake of [ 67 Ga]Ga-DOTA-Miltuximab ® was observed. Liver uptake was reduced by pre-infusion of unlabelled Miltuximab ® -DOTA. Dosimetry analysis showed a favorable exposure profile. [ 67 Ga]Ga-DOTA-Miltuximab ® targeting to tumour sites was observed in two prostate cancer patients who had failed enzalutamide treatment. Higher doses of unlabelled antibody achieved lower liver uptake and increased antibody serum half life., Conclusions: This study is the first in human for Miltuximab ® a first in class antibody targeting GPC-1. The trial met its primary endpoint of safety, demonstrating its potential as a safe and tolerable monoclonal antibody. This safety data, together with targeting to tumour lesions and biodistribution information supports the further clinical development of Miltuximab ® as a theranostic agent in a planned Phase I human trial., (© 2021 mums.ac.ir All rights reserved.)

'Mutated in Colorectal Cancer' (MCC) is emerging as a multifunctional protein that affects several cellular processes and pathways. Although the MCC gene is rarely mutated in colorectal cancer, it is frequently silenced through promoter methylation. Previous studies have reported loss of heterozygosity (LOH) of the closely linked MCC and APC loci in both colorectal and lung cancers. APC promoter methylation is a marker of poor survival in non-small cell lung cancer (NSCLC). However, MCC methylation has not been previously studied in lung cancer. Therefore, we wanted to determine if MCC is silenced through promoter methylation in lung cancer and whether this methylation is associated with LOH of the MCC locus or methylation of the APC gene. Three polymorphic markers for the APC/MCC locus were analysed for LOH in 64 NSCLC specimens and matching normal tissues. Promoter methylation of both genes was determined using methylation specific PCR in primary tumours. LOH of the three markers was found in 41-49% of the specimens. LOH within the MCC locus was less common in adenocarcinoma (ADC) (29%) than in squamous cell carcinoma (SCC) (72%; P=0.006) or large cell carcinoma (LCC) (75%; P=0.014). However, this LOH was not accompanied by MCC promoter methylation, which was found in only two cancers (3%). In contrast, 39% of the specimens showed APC methylation, which was more common in ADC (58%) than in SCC (13%). Western blotting revealed that MCC was expressed in a subset of lung tissue specimens but there was marked variation between patients rather than between cancer and matching non-cancer tissue specimens. In conclusion, we have shown that promoter methylation of the APC gene does not extend to the neighbouring MCC gene in lung cancer, but LOH is found at both loci. The variable levels of MCC expression were not associated with promoter methylation and may be regulated through other cellular mechanisms., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)