ABSTRACT
New approaches to cancer immunotherapy have been developed, showing the ability to harness the immune system to treat and eliminate cancer. For many solid tumors, therapy with checkpoint inhibitors has shown promise. For hematologic malignancies, adoptive and engineered cell therapies are being widely developed, using cells such as T lymphocytes, as well as natural killer (NK) cells, dendritic cells, and potentially others. Among these adoptive cell therapies, the most active and advanced therapy involves chimeric antigen receptor (CAR)-T cells, which are T cells in which a chimeric antigen receptor is used to redirect specificity and allow T cell recognition, activation and killing of cancers, such as leukemia and lymphoma. Two autologous CAR-T products have been approved by several health authorities, starting with the U.S. Food and Drug Administration (FDA) in 2017. These products have shown powerful, inducing, long-lasting effects against B cell cancers in many cases. In distinction to the results seen in hematologic malignancies, the field of using CAR-T products against solid tumors is in its infancy. Targeting solid tumors and trafficking CAR-T cells into an immunosuppressive microenvironment are both significant challenges. The goal of this review is to summarize some of the most recent aspects of CAR-T cell design and manufacturing that have led to successes in hematological malignancies, allowing the reader to appreciate the barriers that must be overcome to extend CAR-T therapies to solid tumors successfully.
ABSTRACT
Cancer stem cells (CSCs) with their self-renewal ability are accepted as cells which initiate tumors. CSCs are regarded as interesting targets for novel anticancer therapeutic agents because of their association with tumor recurrence and resistance to conventional therapies, including radiotherapy and chemotherapy. Chimeric antigen receptor (CAR)-T cells are engineered T cells which express an artificial receptor specific for tumor associated antigens (TAAs) by which they accurately target and kill cancer cells. In recent years, CAR-T cell therapy has shown more efficiency in cancer treatment, particularly regarding blood cancers. The expression of specific markers such as TAAs on CSCs in varied cancer types makes them as potent tools for CAR-T cell therapy. Here we review the CSC markers that have been previously targeted with CAR-T cells, as well as the CSC markers that may be used as possible targets for CAR-T cell therapy in the future. Furthermore, we will detail the most important obstacles against CAR-T cell therapy and suggest solutions.
ABSTRACT
Background: Since the introduction of 4 trocar laparoscope as a golden standard practiced worldwide, there has been an attempt to possibly reduce the number of trocars to achieve better results. Nowadays the alternative 3 or even 2- port LCs have gained attention due to their potential impact on decreasing post-operative pain, leaving less scars behind and maintaining cosmetic superiority. This study aimed at investigating the superiority of 3 port LCs vs the conventional 4 port ones in terms of their technical feasibility, safety and other benefits
Methods: In this clinical trial study, 100 patients with gall bladder stones admitted at Sina Hospital, in Tabriz from Sep. 2013 to Sep. 2014 were randomly divided into two groups of 50 each; one was treated using 4 port technique and the other by means of 3 port technique. Intraoperative findings and postoperative complications were carefully recorded and analyzed
Results: The two parameters- conversion of surgery and bile duct injury- were nil for both groups. Gall bladder perforation in 3- port group happened to be less than 4-port group [17.50 vs 28.50] that is [P=0.027]. No significant difference was reported on other factors including liver bed bleeding or length of operation
Conclusion: The fact that in port 3 LCs the operating time will not take any longer and complications are no more than those in 4-port LCs proves them technically safe and feasible. additionally 3-port LCs have some postoperative advantages such as less scars and maintained cosmetic superiority
ABSTRACT
Objective: OCT4B1, a novel variant of OCT4, is expressed in cancer cell lines and tis-sues. Based on our previous reports, OCT4B1 appears to have a crucial role in regulating apoptosis as well as stress response [heat shock proteins [HSPs]] pathways. The aim of the present study was to determine the effects of OCT4B1 silencing on the expression of high molecular weight HSPs in three different human tumor cell lines
Materials and Methods: In this experimental study, OCT4B1 expression was suppressed in AGS [gastric adenocarcinoma], 5637 [bladder tumor] and U-87MG [brain tumor] cell lines using RNAi strategy. Real-time polymerase chain reaction [PCR] array was employed for expression level analysis and the fold changes were calculated using RT2 Profiler PCR array data analysis software version 3.5
Results: Our data revealed up-regulation of HSPD1 [from HSP60 family] as well as HSPA14, HSPA1L, HSPA4, HSPA5 and HSPA8 [from HSP70 family] following OCT4B1 knock-down in all three cell lines. In contrast, the expression of HSP90AA1 and HSP90AB1 [from HSP90 family] as well as HSPA1B and HSPA6 [from HSP70 family] was down-regulated under similar conditions. Other stress-related genes showed varying expression pattern in the examined tumor cell lines
Conclusion: Our data suggest a direct or indirect correlation between the expression of OCT4B1 and HSP90 gene family. However, OCT4B1 expression was not strongly correlated with the expression of HSP70 and HSP60 gene families
ABSTRACT
Background: recent studies have shown the immunomodulatory effect of vitamin D3 through down-regulation of Toll-like receptor [TLR] expression in human monocytes. In this study, the effects of vitamin D treatment on TLR2 and TLR4 expression on monocytes derived from type 2 diabetes was investigated
Materials and Methods: to assess the influence of vitamin D3 on expression of TLR2 and TLR4 on monocytes from patients with type II diabetes, peripheral blood sample was taken of 30 patients. Peripheral blood mononuclear cells [PBMCs] were isolated by density gradient centrifuge and then monocytes were isolated from these cells with using the magnetic activated cell sorting [MACS]. To investigate the effect of vitamin D3 on the expression of TLR2 and TLR4, monocytes were cultured in the presence of vitamin D3 [10[-9] M] for 48 hours. Then the expression of TLR2 and TLR4 was determined by Real-time PCR
Results: we found that vitamin D3 suppresses the mRNA expression of TLR2 and TLR4 in patients with type II diabetes. TLR2 and TLR4 expression in the patients exposed to vitamin D3 were significantly decreased in comparison with patients who were not treated with vitamin D3
Conclusion: it can be concluded that vitamin D3 supplements may be further analyzed as a therapeutic option by reducing TLR2 and TLR4 expression in patients with type II diabetes
ABSTRACT
Absent in Melanoma 2 [AIM2] is an intracellular microbial dsDNA sensor which plays an important role in production of proinflammatory cytokines through Apoptosis associated Speck-like protein containing a Caspase activation and recruitment domain [ASC] and Caspase-1. Micro-RNAs [miRNAs] play important roles in regulation of immune related genes. However, there is little information regarding the effects of miRNAs on the AIM2 and ASC expression. To determine the mRNA levels of AIM2 and ASC in Jurkat cell line following introducing miRNA-143 [MiR-143]. MiR-143, a scrambled sequence and PBS were introduced separately, to the Jurkat cell lines and the mRNA levels of AIM2 and ASC were examined in parallel with beta-actin and GAPDH [as housekeeping genes] using Real-Time PCR technique. The mRNA levels of AIM2 and ASC were significantly increased in the MiR-143 transfected Jurkat cells when compared to the scrambled sequence or PBS treated cells. MiR-143 can lead to increased expression of AIM2 and ASC mRNAs. Considering the significance of AIM2 and ASC in DNA sensing and inflammosome formation, it can be considered as a therapeutic agent for the treatment of chronic infectious diseases, especially viral infections
ABSTRACT
Chemokines and their receptors are expressed in different types of malignancies. CC chemokines MIP-1alpha [CCL3], MIP-1beta [CCL4] and RANTES [CCL5] is believed to be anti-tumor and also aid to the metastasis in tumor microenvironment. CCR2 and CCR5 are special G-protein receptors for these chemokines. Due to the important role of CCR5 chemokine receptor in tumor biology, this project is designed to examine delta 32 mutation in CCR5 gene regards breast cancer. This experimental study was performed during 2007-8 on delta healthy adults and 36 breast cancer patients by Gap-PCR. The demographic information also was collected by questionner and t-test Chi-square was used for statistical analysis of data. Our results showed that none of breast cancer patients had CCR5-delta 32 mutation while 3 [3%] cases of controls had heterozygotic form of this mutation. Our results showed that there is not any CCR5-delta 32 mutation in patients. Therefore, it appears that this mutation don't play any role in breast cancer
Subject(s)
Humans , Female , Mutation/genetics , Prevalence , Receptors, CCR5/genetics , Chemokines, CC , Surveys and QuestionnairesABSTRACT
Systemic lupus erythematosus [SLE] can affect all organ systems including the respiratory tract and skeletal muscles. Some of the respiratory findings can be attributed to respiratory muscle involvement. The purpose of this study was to clarify the characteristics of pulmonary function tests [PFT], especially maximum inspiratory pressure [MIP] and maximum expiratory pressure [MEP] in females with systemic lupus erythematosus [SLE]. During a 12-mounth period, forced vital capacity [FVC], FEV1, FEF25-75, MIP, and MEP were measured prospectively in 76 consecutive female patients, suffering active SLE. The measured values were compared to an age-matched group of healthy women. FVC was lower in the patients than in controls [2.81versus 3.64] P=0.000. Maximal inspiratory pressure [PImax] was lower in the female patients than in 78 controls [3.42 versus 7.36]P=0.000. Maximal expiratory pressure [PEmax] was lower in the female patients than in controls [4.14versus 9.68 kPa] P=0.000, There were no correlations between PImax or PEmax and parameters of disease activity. Mouth occlusion pressure within the first 0.1 s of inspiration was higher in SLE patients than in controls [2.43 versus 1.38]; however, the difference was not statistically significant [P=0.16]. This study provides evidence of inspiratory and expiratory muscle weakness in SLE and may cause FVC reduction as well. The pathophysiologic mechanisms and the prognostic significance should be further investigated