scholarly journals Combined Therapy with microRNA-Expressing Salmonella and Irradiation in Melanoma

2021 ◽  
Vol 9 (11) ◽  
pp. 2408
Author(s):  
Wonsuck Yoon ◽  
Yongsung Park ◽  
Seunghyun Kim ◽  
Yongkeun Park ◽  
Chul Yong Kim
Keyword(s):  
Radiation Therapy ◽  
Anticancer Drugs ◽  
Combined Therapy ◽  
Treatment Strategies ◽  
Research Strategy ◽  
Combination Strategy ◽  
Resistant Mouse ◽  
Anticancer Efficacy ◽  
Radiation Resistant ◽  
Novel Strategy

Anticancer treatment strategies using bacteria as a vector are currently expanding with the development of anticancer drugs. Here, we present a research strategy to develop anticancer drugs using bacteria that contain miRNAs. We also present a strategy for the development of novel bacterial anticancer drugs in combination with radiation. Salmonella strains expressing miRNA were produced by modifying the miRNA expression vector encoding INHA, a radiation-resistant gene developed previously. The anticancer effect of INHA was confirmed using skin cancer cell lines. We also tested a combination strategy comprising bacteria and radiation for its anticancer efficacy against radiation-resistant mouse melanoma to increase the efficacy of radiation therapy as a novel strategy. The recombinant strain was confirmed to promote effective cell death even when combined with radiation therapy, which exerts its cytotoxicity by enhancing reactive oxygen species production. Moreover, a combination of bacterial and radiation therapy enhanced radiotherapy efficacy. When combined with radiation therapy, bacterial therapy exhibited effective anti-cancer properties even when administered to animals harboring radiation-resistant tumors. This strategy may promote the secretion of cytokines in cells and more effectively reduce the number of bacteria remaining in the animal. Thus, this study may lead to the development of a strategy to improve the effectiveness of radiation therapy using Salmonella expressing cancer-specific miRNA for intractable cancers such as those resistant to radiation.

scholarly journals Lipid–Saporin Nanoparticles for the Intracellular Delivery of Cytotoxic Protein to Overcome ABC Transporter-Mediated Multidrug Resistance In Vitro and In Vivo

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 498
Author(s):  
Guan-Nan Zhang ◽  
Pranav Gupta ◽  
Ming Wang ◽  
Anna Maria Barbuti ◽  
Charles R. Ashby ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Anticancer Drugs ◽  
Tyrosine Kinases ◽  
Cellular Proliferation ◽  
Treatment Strategies ◽  
Anticancer Efficacy

Although the judicious use of anticancer drugs that target one or more receptor tyrosine kinases constitutes an effective strategy to attenuate tumor growth, drug resistance is commonly encountered in cancer patients. The ATP-binding cassette transporters are one of the major contributors to the development of multidrug resistance as their overexpression significantly decreases the intracellular concentration and thus, the efficacy of certain anticancer drugs. Therefore, the development of treatment strategies that would not be susceptible to efflux or excretion by specific ABC transporters could overcome resistance to treatment. Here, we investigated the anticancer efficacy of saporin, a ribosome-inactivating protein. Since saporin has poor permeability across the cell membrane, it was encapsulated in a lipid-based nanoparticle system (EC16-1) that effectively delivered the formulation (EC16-1/saporin) intracellularly and produced anti-cancer efficacy. EC16-1/saporin, at nanomolar concentrations, significantly inhibited the cellular proliferation of parental and ABCB1- and ABCG2-overexpressing cancer cells. EC16-1/saporin did not significantly alter the subcellular localization of ABCB1 and ABCG2. In addition, EC16-1/saporin induced apoptosis in parental and ABCB1- and ABCG2-overexpressing cancer cells. In a murine model system, EC16-1/saporin significantly inhibited the tumor growth in mice xenografted with parental and ABCB1- and ABCG2-overexpressing cancer cells. Our findings suggest that the EC16-1/saporin combination could potentially be a novel therapeutic treatment in patients with parental or ABCB1- and ABCG2-positive drug-resistant cancers.

scholarly journals Downregulation of MicroRNA-330 Correlates with the Radiation Sensitivity and Prognosis of Patients with Brain Metastasis from Lung Cancer

2017 ◽  
Vol 42 (6) ◽  
pp. 2220-2229 ◽  
Author(s):  
Li-Peng Jiang ◽  
Zhi-Tu Zhu ◽  
Yue Zhang ◽  
Chun-Yan He
Keyword(s):  
Lung Cancer ◽  
Logistic Regression ◽  
Radiation Therapy ◽  
Survival Rate ◽  
Brain Metastasis ◽  
Cox Regression ◽  
Radiation Sensitivity ◽  
Extracranial Metastasis ◽  
Radiation Resistant ◽  
N Stage

Background: The present study sought to explore the role of microRNA-330 (miR-330) in predicting the radiation response and prognosis of patients with brain metastasis (BM) from lung cancer (LC). Methods: Patients with BM from LC were identified and classified into radiation-sensitive and radiation-resistant groups according to the overall survival rate, local and distant recurrence rate after conventional whole-brain radiation therapy. Quantitative realtime polymerase chain reaction (qRT-PCR) was used to detect miR-330 expression in serum. Receiver operating characteristic (ROC) curves were used to evaluate the prognostic value of miR-330 for the radiation sensitivity of brain metastasis from LC. Related clinical factors for radiation sensitivity were assessed by logistic regression analysis, and a survival analysis was conducted using COX regression and the Kaplan-Meier method. Results: MiR-330 exhibited lower expression in the radiation-sensitive group than in the radiation-resistant group. The area under the ROC curve of miR-330 for predicting radiation sensitivity was 0.898 (optimal cut-off value, 0.815), with a sensitivity of 71.7% and a specificity of 90.1%. After radiation therapy, patients with low miR-330 expression, compared to patients with high miR-330 expression, displayed a lower survival rate and a median survival time. MiR-330 expression was correlated with extracranial metastasis, maximum BM diameter, tumor-node-metastasis (TNM) stage and node (N) stage. Logistic regression and COX regression analyses revealed that extracranial metastasis, TNM stage, N stage and miR-330 expression were factors that influenced both radiation sensitivity and individual prognostic factors in patients with BM from LC. Conclusions: These findings indicate that the downregulation of miR-330 correlates with radiation sensitivity and poor prognosis in patients with BM from LC.

scholarly journals Nanoparticle-Mediated Tumor Vascular Disruption: A Novel Strategy in Radiation Therapy

2016 ◽  
Vol 96 (2) ◽  
pp. S97 ◽  
Author(s):  
S. Kunjachan ◽  
A. Detappe ◽  
R. Kumar ◽  
S. Sridhar ◽  
M. Makrigiorgos ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Vascular Disruption ◽  
Novel Strategy

scholarly journals The Multidrug Resistance-Reversing Activity of a Novel Antimicrobial Peptide

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1963
Author(s):  
Qiu-Xu Teng ◽  
Xiaofang Luo ◽  
Zi-Ning Lei ◽  
Jing-Quan Wang ◽  
John Wurpel ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Antimicrobial Peptides ◽  
Anticancer Drugs ◽  
Anticancer Agents ◽  
Abc Transporters ◽  
Intracellular Accumulation ◽  
The Past ◽  
Novel Strategy ◽  
New Generation ◽  
Abcb1 Transporter

The overexpression of ATP-binding cassette (ABC) transporters is a common cause of multidrug resistance (MDR) in cancers. The intracellular drug concentration of cancer cells can be decreased relative to their normal cell counterparts due to increased expression of ABC transporters acting as efflux pumps of anticancer drugs. Over the past decades, antimicrobial peptides have been investigated as a new generation of anticancer drugs and some of them were reported to have interactions with ABC transporters. In this article, we investigated several novel antimicrobial peptides to see if they could sensitize ABCB1-overexpressing cells to the anticancer drugs paclitaxel and doxorubicin, which are transported by ABCB1. It was found that peptide XH-14C increased the intracellular accumulation of ABCB1 substrate paclitaxel, which demonstrated that XH-14C could reverse ABCB1-mediated MDR. Furthermore, XH-14C could stimulate the ATPase activity of ABCB1 and the molecular dynamic simulation revealed a stable binding pose of XH-14C-ABCB1 complex. There was no change on the expression level or the location of ABCB1 transporter with the treatment of XH-14C. Our results suggest that XH-14C in combination with conventional anticancer agents could be used as a novel strategy for cancer treatment.

scholarly journals CDK4/6 inhibitors: a novel strategy for tumor radiosensitization

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Yilan Yang ◽  
Jurui Luo ◽  
Xingxing Chen ◽  
Zhaozhi Yang ◽  
Xin Mei ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Clinical Studies ◽  
Cell Cycle Progression ◽  
Combined Therapy ◽  
Small Sample ◽  
Combination Strategies ◽  
Novel Strategy ◽  
Underlying Mechanisms

Abstract Recently, the focus of enhancing tumor radiosensitivity has shifted from chemotherapeutics to targeted therapies. Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors are a novel class of selective cell cycle therapeutics that target the cyclin D-CDK4/6 complex and induce G1 phase arrest. These agents have demonstrated favorable effects when used as monotherapy or combined with endocrine therapy and targeted inhibitors, stimulating further explorations of other combination strategies. Multiple preclinical studies have indicated that CDK4/6 inhibitors exhibit a synergistic effect with radiotherapy both in vitro and in vivo. The principal mechanisms of radiosensitization effects include inhibition of DNA damage repair, enhancement of apoptosis, and blockade of cell cycle progression, which provide the rationale for clinical use. CDK4/6 inhibitors also induce cellular senescence and promote anti-tumor immunity, which might represent potential mechanisms for radiosensitization. Several small sample clinical studies have preliminarily indicated that the combination of CDK4/6 inhibitors and radiotherapy exhibited well-tolerated toxicity and promising efficacy. However, most clinical trials in combined therapy remain in the recruitment stage. Further work is required to seek optimal radiotherapy-drug combinations. In this review, we describe the effects and underlying mechanisms of CDK4/6 inhibitors as a radiosensitizer and discuss previous clinical studies to evaluate the prospects and challenges of this combination.

Optimizing Sequence of PD-L1 Immune-Checkpoint Inhibitors and Radiation Therapy in Bladder Cancer

2020 ◽  
Vol 6 (3) ◽  
pp. 295-302
Author(s):  
Côme Tholomier ◽  
Gautier Marcq ◽  
Surashri Shinde-Jadhav ◽  
Mina Ayoub ◽  
Jia Min Huang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Radiation Therapy ◽  
Tumor Growth ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Combined Therapy ◽  
Tumor Growth Rate ◽  
Significant Difference ◽  
Rate Of Response

BACKGROUND: New bladder preserving strategies are needed for muscle invasive bladder cancer (MIBC). Combined therapy of immune-checkpoint inhibitors and radiation was shown to have synergistic antitumoral effects in preclinical studies. OBJECTIVES: We aim to evaluate whether the sequence of administration of this combined therapy impacts antitumoral response. METHODS: We developed an in-vivo syngeneic MIBC mouse model where murine bladder cancer cells (MB49) were injected subcutaneously in the right flank of C57BL/6 mice. Mice were then randomized to the following treatments: control, anti-programmed cell death ligand 1 (PD-L1) alone, radiation alone (XRT) consisting of 6.25 Gy x2 fractions, concurrent anti-PD-L1 with XRT, neoadjuvant anti-PD-L1 followed by XRT, or XRT followed by adjuvant anti-PD-L1 therapy. Tumor growth, survival, and rate of response were analyzed. RESULTS: Total of 60 mice were randomized. One-way analysis of variance showed statistically significant difference in tumor growth rate across the treatment arms (p = 0.029). Importantly, timing of immunotherapy (neoadjuvant, concurrent, or adjuvant) did not alter either tumor growth or survival (p > 0.05). The rate of response was also similar in each combination arm (p > 0.05). CONCLUSION: Combining anti-PD-L1 immunotherapy and radiation therapy offers optimal antitumoral responses. Timing of immunotherapy (neoadjuvant, concurrent, or adjuvant) does not appear to affect outcomes. Whether the toxicity profile differs across various sequential deliveries of combination therapy requires further evaluation.

scholarly journals Idiopathic Radiation Recall Dermatitis Developing Nine Months after Cessation of Cisplatin Therapy in Treatment of Squamous Cell Carcinoma of the Tonsil

2012 ◽  
Vol 2012 ◽  
pp. 1-3 ◽  
Author(s):  
Stephen M. Melnyk ◽  
Kenneth F. More ◽  
Edward F. Miles
Keyword(s):  
Squamous Cell Carcinoma ◽  
Radiation Therapy ◽  
Radiation Dose ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Combined Therapy ◽  
Suspected Case ◽  
Radiation Recall ◽  
Radiation Recall Dermatitis ◽  
Recall Dermatitis

To report on a suspected case of idiopathic radiation recall dermatitis in an individual nine months after radiation and chemotherapy treatment of squamous cell carcinoma of the right tonsil. Radiation recall dermatitis is the development of a reaction in a previously irradiated area of skin after the administration of an aggravating medication. A review of the literature revealed several cases of radiation recall dermatitis that occur following radiation therapy and the institution of chemotherapy. Other medications have also been implicated in radiation recall dermatitis; however, this patient has not started any new medications since completion of his combined therapy. The patient developed this skin reaction in a distribution pattern identical to the area that received the highest radiation dose suggesting a possible link between radiation recall dermatitis and radiation dose. Radiation recall dermatitis is a reaction that is typically seen shortly after the reinstitution of chemotherapy during radiation therapy. This case illustrates that other medical etiologies are possible and suggests a relationship between radiation recall dermatitis and the total radiation dose an area receives.

scholarly journals The microenvironment in mature B-cell malignancies: a target for new treatment strategies

Blood ◽  
2009 ◽  
Vol 114 (16) ◽  
pp. 3367-3375 ◽  
Author(s):  
Jan A. Burger ◽  
Paolo Ghia ◽  
Andreas Rosenwald ◽  
Federico Caligaris-Cappio
Keyword(s):  
B Cell ◽  
Residual Disease ◽  
Current Knowledge ◽  
Treatment Strategies ◽  
B Cell Malignancies ◽  
Accessory Cells ◽  
Specialized Tissue ◽  
New Treatment ◽  
Novel Strategy ◽  
Secondary Lymphoid Organs

AbstractDespite major therapeutic advances, most mature B-cell malignancies remain incurable. Compelling evidence suggests that crosstalk with accessory stromal cells in specialized tissue microenvironments, such as the bone marrow and secondary lymphoid organs, favors disease progression by promoting malignant B-cell growth and drug resistance. Therefore, disrupting the crosstalk between malignant B cells and their milieu is an attractive novel strategy for treating selected mature B-cell malignancies. Here we summarize the current knowledge about the cellular and molecular interactions between neoplastic B lymphocytes and accessory cells that shape a supportive microenvironment, and the potential therapeutic targets that are emerging, together with the new problems they raise. We discuss clinically relevant aspects and provide an outlook into future biologically oriented therapeutic strategies. We anticipate a paradigm shift in the treatment of selected B-cell malignancies, moving from targeting primarily the malignant cells toward combining cytotoxic drugs with agents that interfere with the microenvironment's proactive role. Such approaches hopefully will help eliminating residual disease, thereby improving our current therapeutic efforts.

Sign in / Sign up

Export Citation Format

Share Document