Clinical trials of cellular therapies for the treatment of colorectal cancer: a narrative review

Colorectal cancer (CRC) treatment using common chemotherapy approaches has drawbacks such as side effects, costs, and resistance of cancer cells which affects patients’ prolonged survival, and quality of life. The immune cells have pivotal roles in regulating tumor progression in the tumor microenvironment (TME). The most important CRC cellular immunotherapies include the use of tumor-derived cells such as tumor-infiltrating lymphocytes (TILs) and lymph node lymphocytes (LNLs), peripheral blood mononuclear cells (PBMCs), derived cells, including T cells, natural killer (NK) cells, cytokine-induced killer (CIK) cells, and chimeric antigen receptor (CAR) cells. Although adoptive cell therapy has some advantages, some disadvantages have been reported. TILs cells are strictly directed against tumor-specific antigens; however, they are inefficient due to immune editing. CIK cells have a major histocompatibility complex (MHC)-independent cytotoxic effect and need concurrent high-dose interleukin (IL)-2 administration. In addition, chimeric antigen receptor-T cells (CAR-T cells) are MHC-independent that overcome MHC downregulation by the tumor. They are potent in recognizing any cell surface antigen and are applicable to a broad range of patients and T-cell populations. Here, the researchers present the most popular cancer cellular immunotherapy approaches and discuss their clinical relevance by referring to data obtained from CRC clinical trials. To date, clinical experience and efficacy suggest that combining more than one immunotherapy intervention, in combination with other treatments like chemotherapy, radiotherapy, and targeted therapy, is promising for cancer therapy

Curcuma purpurascens BI. rhizome accelerates rat excisional wound healing: involvement of Hsp70/Bax proteins, antioxidant defense, and angiogenesis activity

Elham Rouhollahi,1 Soheil Zorofchian Moghadamtousi,2 Fatemeh Hajiaghaalipour,3 Maryam Zahedifard,2 Faezeh Tayeby,2 Khalijah Awang,4 Mahmood Ameen Abdulla,3 Zahurin Mohamed1 1Pharmacogenomics Laboratory, Department of Pharmacology, Faculty of Medicine, 2Institute of Biological Sciences, Faculty of Science, 3Department of Biomedical Science, Faculty of Medicine, 4Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia Purpose: Curcuma purpurascens BI. is a member of Zingiberaceae family. The purpose of this study is to investigate the wound healing properties of hexane extract of C. purpurascens rhizome (HECP) against excisional wound healing in rats.Materials and methods: Twenty four rats were randomly divided into 4 groups: A) negative control (blank placebo, acacia gum), B) low dose of HECP, C) high dose of HECP, and D) positive control, with 6 rats in each group. Full-thickness incisions (approximately 2.00 cm) were made on the neck area of each rat. Groups 1–4 were treated two-times a day for 20 days with blank placebo, HECP (100 mg/kg), HECP (200 mg/kg), and intrasite gel as a positive control, respectively. After 20 days, hematoxylin and eosin and Masson’s trichrome stainings were employed to investigate the histopathological alterations. Protein expressions of Bax and Hsp70 were examined in the wound tissues using immunohistochemistry analysis. In addition, levels of enzymatic antioxidants and malondialdehyde representing lipid peroxidation were measured in wound tissue homogenates.Results: Macroscopic evaluation of wounds showed conspicuous elevation in wound contraction after topical administration of HECP at both doses. Moreover, histopathological analysis revealed noteworthy reduction in the scar width correlated with the enhanced collagen content and fibroblast cells, accompanied by a reduction of inflammatory cells in the granulation tissues. At the molecular level, HECP facilitates wound-healing process by downregulating Bax and upregulating Hsp70 protein at the wound site. The formation of new blood vessel was observed in Masson’s trichrome staining of wounds treated with HECP (100 and 200 mg/kg). In addition, HECP administration caused a significant surge in enzymatic antioxidant activities and a decline in lipid peroxidation.Conclusion: These findings suggested that HECP accelerated wound-healing process in rats via antioxidant activity, angiogenesis effect and anti-inflammatory responses involving Hsp70/Bax. Keywords: Zingiberaceae, wound closure, immunohistochemistry, antioxidant enzyme activity, inflammatory cell