جستجوی مقالات مرتبط با کلیدواژه « oncolytic virus » در نشریات گروه « پزشکی »

According to numerous studies, colorectal cancer will probably become more common over the next few decades. This phenomenon causes by population growth, ageing, and rising rates of crucial risk factors from people's lifestyle, such as idleness and malnutrition. The approach of Surgery to remove malignancies is typically the first step of colon cancer treatment. There may also be a recommendation for additional therapies like chemotherapy and radiation therapy. However, there is always a need to develop novel cancer treatment strategies due to drug resistance and lack of targeted approaches. This study aimed to evaluate the effects of oncolytic Coxsackievirus A21 on the colorectal cancer mouse model.

Colorectal cancer mouse modelling was carried out by injecting 5×106 CT-26 cells (a colonic carcinoma cell line) into the left flank of female BALB/c mice. After noticing the palpable tumor, proceed to treat them with oncolytic Coxsackievirus A21 (106 TCID50/ml, twice at one-week interval). The mice in each group were put to death ten days after the last therapy to assess the efficacy of the treatment.

The present study results demonstrated that treatment with Coxsackievirus A21 increased the level of NO production, LDH, and IFN-γ levels and significantly reduced the secretion of IL-4, IL-10, and TGF-β in compared with control group.

In our mouse model of colorectal cancer, the Coxsackievirus A21 therapy encouraged favorable outcomes. The current study also showed that inducing innate anti-tumor immunity, which was more potent than that seen with monotherapy, and immune deviation from anti-inflammatory cytokines (like IL-4, IL-10, and TGF-β) to pro-inflammatory cytokine IFN-γ might contribute to the beneficial effects of the combination.

Colorectal cancer (CRC) is a common type of cancer that has a high death rate and is be- coming more common in developed countries. Currently, there are several treatment options available for CRC patients, and clinical trials are being conducted to improve conventional therapies. This study investigates the combined impact of Bacillus coagulans (B.C) and Newcastle disease virus (NDV) on the growth of human colorectal adenocarcinoma cells (HT29 cell line).

The HT29 cell line was cultured under controlled laboratory conditions. They were treated with Fluorouracil (5-FU), NDV, and B.C., after which various assessments were conducted to determine the effects of these treat- ments. These assessments included MTT assay for cytotoxicity, evaluation of cell viability, and measurement of caspase 8 and 9 activity levels. The significance of the data was determined at a threshold of P<0.05 following analysis.

The usage of NDV and B.C significantly increased cell death and reduced cell growth in the HT29 cell line, when compared to the control group. Moreover, the combined application of NDV and B.C along with 5-FU exhibited a synergistic effect in decreasing the proliferation of HT29 cells. Additionally, the results indicated that intrinsic apoptosis pathway was activated by B.C and NDV.

It appears that utilizing oncolytic viruses (OV) and bacteria in conjunction with chemotherapy drugs could potentially aid in reducing the growth of colorectal cancer cells. However, further research is necessary, including animal studies, to confirm the efficacy of this treatment method.

Autophagy is a highly conserved mechanism in eukaryotic cells which removes the dysfunctional organelles from the cell. Autophagy has immense physiological and pathological roles in cells. There are a variety of reports showing the dual function of autophagy as a tumor suppression and promotion phenomenon. Therefore, targeted therapy approaches like virotherapy can be a promising cancer treatment. Vesicular stomatitis virus (VSV) is a well-known oncolytic virus which mutations in its matrix (M) protein including M51R, make it a better candidate for oncotargeting. Moreover, beclin-1 is one of the key regulators of autophagy and also apoptosis.

In the present study, the level of autophagy markers such as beclin-1 and LC3 were investigated concerning the apoptosis process induction by VSV M-protein. Two colorectal cancer cell lines HCT116 and SW480 and one normal colon epithelial cell line (FHC) which expressing VSV M51R mutant M-protein were compared regarding autophagy versus apoptosis. All experiments were conducted at least in triplicate.

The results showed that the elevated level of caspase 3 and reduced amount of beclin-1 in transfected SW480 cells may be an acceptable description for apoptosis.

In HCT116 cells domination of autophagy, plays a supportive mechanism for the cells to survive in response to M51R M-protein stress. Suppression of autophagy as an adjunct can be a promising way to eliminate resistance to cancer treatment. We have quantitively evaluated the Beclin-1 and LC3-II as autophagy markers, Future evaluation of these two along with other markers like P62 will reduce the limitations of this study.

Reovirus type 3 Dearing (ReoT3D), a wild type oncolytic virus (OV) from the Reoviridae family, kills KRAS mutant cancer cells. However, the use of oncolytic viruses (OVs) has faced with some limitations such as immune responses, and delivery of OVs to the tumor sites in systemic therapy. To solve this, and also to increase the anti-cancer effects of these OVs, mesenchymal stem cells (MSCs) might be used as an effective vehicle for OVs delivery. In this study, we examined the anti-cancer effects of human Adipose Derived-MSCs (AD-MSCs) as a vehicle of ReoT3D against human gliobastoma cells.

Here, AD-MSCs were characterized and toxicity of ReoT3D on them was determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Then, capability of AD-MSCs for virus production was assessed by real-time PCR, and different in vitro anti-cancer experiments were applied for our anti-cancer purposes.

Our results from toxicity assay revealed that the isolated and provoked AD-MSCs were resistant to nontoxic concentration multiplicity of infection (MOI) >1 pfu/cells of ReoT3D. In addition, the results indicated that AD-MSCs were susceptible for virus life cycle complementation and were capable for production of virus progenies. Furthermore, our results showed that AD-MSCs had oncolysis effects and increased the anti-cancer effects of ReoT3D.

AD-MSCs as a susceptible host for oncolytic reovirus could increase the anti-cancer activity of this OV against glioblastoma multiforme (GBM) cell line.

Huh-7 is a cell line that was derived from a liver tumor of a Japanese man. Hepatocellular carcinoma (HCC) is considered as a primary liver cancer. Highly resistant tumor to treatment which causes the death of many patients annually. Thus, targeting the cancer cells by using a new method could be effective in therapy of this cancer. Reoviruses are oncolytic viruses that can infect and kill tumor cells, which have an activated Ras signaling pathways, while normal cells are resistant to infection and replication of these viruses. The aim of this study was to evaluate the effect of oncolytic human reovirus on Huh 7 cell line in vitro.

Human reovirus serotype 3, Huh-7 cell line, and normal human fibroblasts were used in this study. After virus purification and plaque assay, human reoviruses were inoculated into the Huh-7 cells and human normal fibroblasts as negative control. Virus cytopathic effect, cell viability, and viral RNA replication were assessed at the different time of post-infection.

Virus cytopathic effects and cell lysis were clearly observed and reovirus RNA replication was detected in the Huh-7 cells, whereas normal human fibroblasts were resistant against reovirus infection.

The result of the present study showed that human reoviruses serotype 3 can destroy the Huh-7 cells. Accordingly, the use of human reovirus could be considered as a potential therapy for HCC and liver cancer.

Oncolytic Herpes simplex virus type 1 (HSV-1) has emerged as a promising strategy for cancer therapy. However, development of novel oncolytic mutants has remained a major challenge owing to low efficiency of conventional genome editing methods. Recently, CRISPR-Cas9 has revolutionized genome editing. In this study, we aimed to evaluate the capability of CRISPR-Cas9 to manipulate the UL39 gene to create oncolytic HSV-1. Herein, three sgRNAs were designed against the UL39 gene and transfected into HEK-293 cell line followed by infection with HSV-1 KOS. After three rounds of plaque purification, several HSV-1 mutants were identified by PCR analysis and sequencing. One of these mutations in which 55 nucleotides were deleted resulted in a frameshift mutation that in turn produced a truncated protein with only 167 amino acids from 1137 amino acids. Functional analysis in Vero and primary fibroblast cells revealed that viral replication was significantly lower and plaque size was smaller in the HSV-1 mutant compared with HSV-1 KOS. Moreover, the relative amount of viral genome present in the supernatants of infected cells (Vero and primary fibroblast cells) with HSV-1 mutant was significantly decreased compared with those of HSV-1 KOS. Our data revealed that targeting UL39 with CRISPR-Cas9 could develop oncolytic HSV-1.

The  ability  of  the  reovirus  to  destroy  various  cancer  cells  in  vitro  and,  the  success  of  the  virus  in  conducting  clinical  trial  phases  of  cancer  therapy  has  attracted  the  attention  of  researchers  toward  the  virus.  One  of  the  main  needs  for  the  investigation  of  the  viral  effects  and  the  virus-host  cell  interaction  is  preparation  of  the  purified  virus.  Most  of  the  protocols  have  been  based  on  the  use  of  suspended  cell  culture  equipment  that  normally  does  not  exist  in  the  research  laboratories.  We  optimized  a  virus  purification  method  that  was  based  on  using  cell  culture  flask  and  adherent  cells.

L-929 cells were used for reovirus propagation.  After sufficient CPE, the cells were collected and pelleted.  Using  Vertrel-XF  treatment  and  ultracentrifugation  on  the  cesium  chloride  (CsCl)  gradient,  purified  reovirus  was  obtained.  It  was  subsequently  concentrated  by  filtration  using  a  100kDa  Amicon  unit.  Finally,  infectivity  and  the  number  of  purified  human  reoviruses  were  evaluated  by  plaque  assay. The  band  of  purified  human  reovirus  was  aspirated  form  the  ultracentrifugation  tube  and  then  was  dialysed  and  concentrated  by  filtration  in  Amicon  unit.  The  titer  of  purified  human  reovirus  was  determined to be  3×1012  PFUs/ml.

In  present  study,  we  established  a  protocol  for  the  purification  of  human  reovirus  without  need  for  equipment  of  suspension  cell  culture. 

Although,  the  time-consuming  dialysis  procedure  was  removed  from  the  end  of  the  work  and  replaced  with  a  rapid  and  simple  filtration  method,  the  high  titer  of  purified  human  reovirus  was  acquired.