Near infrared photoimmunotherapy (NIR-PIT) is a newly developed molecular targeted cancer treatment, which selectively kills cancer cells or immune-regulatory cells and induces therapeutic host ...immune responses by administrating a cancer targeting moiety conjugated with IRdye700. The local exposure to near-infrared (NIR) light causes a photo-induced ligand release reaction, which causes damage to the target cell, resulting in immunogenic cell death (ICD) with little or no side effect to the surrounding normal cells. Moreover, NIR-PIT can generate an immune response in distant metastases and inhibit further cancer attack by combing cancer cells targeting NIR-PIT and immune regulatory cells targeting NIR-PIT or other cancer treatment modalities. Several recent improvements in NIR-PIT have been explored such as catheter-driven NIR light delivery, real-time monitoring of cancer, and the development of new target molecule, leading to NIR-PIT being considered as a promising cancer therapy. In this review, we discuss the progress of NIR-PIT, their mechanism and design strategies for cancer treatment. Furthermore, the overall possible targeting molecules for NIR-PIT with their application for cancer treatment are briefly summarised.
Traditional immunohistochemistry (IHC) has already become an essential method of diagnosis and therapy in cancer management. However, this antibody-based technique is limited to detecting a single ...marker per tissue section. Since immunotherapy has revolutionized the antineoplastic therapy, developing new immunohistochemistry strategies to detect multiple markers simultaneously to better understand tumor environment and predict or assess response to immunotherapy is necessary and urgent. Multiplex immunohistochemistry (mIHC)/multiplex immunofluorescence (mIF), such as multiplex chromogenic IHC and multiplex fluorescent immunohistochemistry (mfIHC), is a new and emerging technology to label multiple biomarkers in a single pathological section. The mfIHC shows a higher performance in cancer immunotherapy. This review summarizes the technologies, which are applied for mfIHC, and discusses how they are employed for immunotherapy research.
Triple-negative breast cancer (TNBC) is a group of heterogeneous and refractory breast cancers with the absence of estrogen receptor (ER), progesterone receptor (PgR) and epidermal growth factor ...receptor 2 (HER2). Over the past decade, antibody drug conjugates (ADCs) have ushered in a new era of targeting therapy. Since the epidermal growth factor receptor (EGFR) and epithelial cell adhesion molecule (EpCAM) are over expressed on triple-negative breast cancer, we developed novel ADCs by conjugating benzylguanine (BG)-modified monomethyl auristatin E (MMAE) to EpCAM- and EGFR-specific SNAP-tagged single chain antibody fragments (scFvs). Rapid and efficient conjugation was achieved by SNAP-tag technology. The binding and internalization properties of scFv-SNAP fusion proteins were confirmed by flow cytometry and fluorescence microscopy. The dose-dependent cytotoxicity was evaluated in cell lines expressing different levels of EGFR and EpCAM. Both ADCs showed specific cytotoxicity to EGFR or EpCAM positive cell lines via inducing apoptosis at a nanomolar concentration. Our study demonstrated that EGFR specific scFv-425-SNAP-BG-MMAE and EpCAM-specific scFv-EpCAM-SNAP-BG-MMAE could be promising ADCs for the treatment of TNBC.
In the last few decades, antibody-based diagnostic and therapeutic applications have been well established in medicine and have revolutionized cancer managements by improving tumor detection and ...treatment. Antibodies are unique medical elements due to their powerful properties of being able to recognize specific antigens and their therapeutic mechanisms such as blocking specific pathways, antibody-dependent cellular cytotoxicity, and complement-dependent cytotoxicity. Furthermore, modification techniques have paved the way for improving antibody properties and to develop new classes of antibody-conjugate-based diagnostic and therapeutic agents. These techniques allow arming antibodies with various effector molecules. However, these techniques are utilizing the most frequently used amino acid residues for bioconjugation, such as cysteine and lysine. These bioconjugation approaches generate heterogeneous products with different functional and safety profiles. This is mainly due to the abundance of lysine and cysteine side chains. To overcome these limitations, different site-direct conjugation methods have been applied to arm the antibodies with therapeutic or diagnostics molecules to generate unified antibody conjugates with tailored properties. This review summarizes some of the enzyme-based site-specific conjugation approaches.
This study aims to investigate the types of impoliteness strategies used in Putin's speech at the annexation ceremony. All of Putin's speeches were intentionally delivered to cause damage to the ...hearers' negative and positive faces. Culpeper's (2011) classifications of impoliteness, which consist of five strategies that are the opposite of politeness, were adopted. Both qualitative and quantitative analyses have been used to accomplish the study objectives. Putin mostly used the negative impoliteness strategy, directly attacking the West and their policies. Furthermore, he considered his authority to be higher than Kyiv and the West, and for this reason, he insulted, belittled, blamed, and accused them. In several texts, he used "bald on record" in a direct, concise, and clear tone when he talked to the President of Ukraine and his elites. The two remaining strategies, positive impoliteness and mock impoliteness, were rarely used. This work contributes to understanding the messages that Putin tried to convey and analyzes them politically.
The higher education sector has witnessed a drastic change due to new advanced technologies including computers and smartphones. As a result, higher education will need to establish a solid ...foundation aided by information communication technologies (ICT) where mobile applications can extend learning opportunities for students and graduates so they meet the requirements of the fast-changing jobs market. Many studies conducted in various contexts have revealed the drastic change of using mobile applications (henceforth apps) and advanced communication which help students develop their skills by means of using the digital environment.
The study aims at identifying the general impression of Iraqi private universities students about the future role of ICT and the mobile learning in higher education. Al-Maarif University College is selected as a case study to measure the extent of students’ reliance on the use of modern smartphones applications in research, study, and skills development in the field of specialization. The study also sheds light upon specifying the important variables and methods for enhancing the role of the mobile learning as a part of the electronic education for the private education sector in Iraq.
The present study aimed to evaluate the effect of knowing a second language (i.e., English) on learning a third language (i.e., Indonesian). In total, 40 Iraqi learners attending a general Indonesian ...course were selected and divided into two groups. The first group included 20 students who had different levels of English language proficiency in addition to their mother tongue (i.e., Arabic). The second group encompassed 20 students who only knew their mother tongue. Their final exam scores were the criteria for determining their third language achievement. According to the results, bilingualism of the participants (familiarity with English as a second/foreign language) positively affected their level of achievement in the third language (Indonesian). Therefore, English language proficiency was a key factor for these students' success in learning a third language. Overall, familiarity with a second language seems to influence the level of competence in a third language.
This paper explores selected aggressive and offensive spoken or written discourse material used by the American ex-president Donald Trump at different periods of time during his rule as the United ...States of America president. The data analysis model will be mainly conducted within the terminology and framework of Van Dijk’s model of critical discourse analysis (henceforth CDA). The research has adopted ten ideological categories to reveal the extent of power, racism and racial discrimination. The current study has mainly investigated how language is structured to show various meanings that indicate the relation of power used in social contexts. The study also tries to show the role of CDA in analyzing elements of power and hegemony and how language users operate them to achieve the goal of successful communication among participants. The abuse is resulted from the use of power as exercised by language users. The way language is perceived and manipulated can identify ideologies imposed by speakers, resulting in controlling addressees through power dominance. The primary objective of this research is to demonstrate the extent to which social power, abuse, and other unpleasant expressions are used in Trump’s political speeches. The research indicates that the majority of Trump’s spoken or written speech methods contain aspects of language that violate social norms and convey a sense of authority and superiority over other addressees.