Effective treatment of mouse metastatic prostate cancer by low electric field enhanced chemotherapy

Plotnikov, A.N.; Niego, Be׳eri; Ophir, R; Korenstein, Rafi; Keisari, Yona

doi:10.1002/pros.20435

Cited by 16 publications

(6 citation statements)

References 19 publications

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“…Our results agreed with those of previous studies . Our results were also supported by the basic research studies that have shown that CT or radiotherapy is more effective in immunocompetent mice than in immunodeficient mice and that immunosuppression counteracts the effect of CRT . The attraction of increased numbers of TILs before neoadjuvant treatment was reported to imply that a tumor was originally immunogenic .…”

Section: Discussionsupporting

confidence: 92%

Significance of tumor‐infiltrating lymphocytes before and after neoadjuvant therapy for rectal cancer

et al. 2018

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Neoadjuvant therapy for locally advanced rectal cancer is becoming increasingly common. However, biomarkers predicting the response to neoadjuvant therapy have not been established. Tumor‐infiltrating lymphocytes (TILs) have a crucial effect on tumor progression and survival outcome as the primary host immune response, and an antitumor immune effect has been reported to contribute to the response to radiotherapy and chemotherapy. We investigated the significance of TILs before and after neoadjuvant treatment and the change in the density of those TILs. Sixty‐four patients who underwent radical resection after neoadjuvant treatment for locally advanced rectal cancer were enrolled. The number of TIL subsets was examined using immunohistochemical staining of pretreatment biopsy samples and post‐treatment resected specimens. In both the neoadjuvant chemotherapy cohort and the neoadjuvant chemoradiotherapy cohort, a low density of CD8+ TILs in pretreatment biopsy samples was associated with a poor response, and a low density of CD8+ TILs in post‐treatment resected specimens was similarly associated with a poor response. In the neoadjuvant chemoradiotherapy cohort, the density of CD8+ TILs in post‐treatment resected specimens was significantly increased compared with that in pretreatment biopsy samples. We concluded that T lymphocyte‐mediated immune reactions play an important role in tumor response to neoadjuvant treatment for rectal cancer, and the evaluation of TILs in pretreatment biopsy samples might be a predictor of the clinical effectiveness of neoadjuvant treatment. Furthermore, neoadjuvant therapy, especially chemoradiotherapy, could induce the activation of the local immune status.

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Section: Discussionsupporting

confidence: 92%

Significance of tumor‐infiltrating lymphocytes before and after neoadjuvant therapy for rectal cancer

et al. 2018

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“…39 These locally amplified fields are thought to inhibit cell proliferation. 39 The enhancement of the chemotherapeutic effect by electric fields, electrochemotherapy, [40][41][42][43] is believed to result from the synergy between the chemotherapeutic drug and field-induced electroporation of metastatic cell membranes. 43 The model reaction studied in this paper, the double proton transfer in the formic acid dimer (or related dimers), has been studied primarily in the absence of external fields.…”

Section: Introductionmentioning

confidence: 99%

Effects of external electric fields on double proton transfer kinetics in the formic acid dimer

Arabi

Matta

2011

Phys. Chem. Chem. Phys.

134

124

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Molecules can be exposed to strong local electric fields of the order of 10(8)-10(10) V m(-1) in the biological milieu. The effects of such fields on the rate constant (k) of a model reaction, the double-proton transfer reaction in the formic acid dimer (FAD), are investigated. The barrier heights and shapes are calculated in the absence and presence of several static homogenous external fields ranging from 5.14 × 10(8) to 5.14 × 10(9) V m(-1) using density functional theory (DFT/B3LYP) and second order Møller-Plesset perturbation theory (MP2) in conjunction with the 6-311++G(d,p) Pople basis set. Conventional transition state theory (CTST) followed by Wigner tunneling correction is then applied to estimate the rate constants at 25 °C. It is found that electric fields parallel to the long axis of the dimer (the line joining the two carbon atoms) lower the uncorrected barrier height, and hence increase the raw k. These fields also flatten the potential energy surface near the transition state region and, hence, decrease the multiplicative tunneling correction factor. The net result of these two opposing effects is that fields increase k(corrected) by a factor of ca. 3-4 (DFT-MP2, respectively) compared to the field-free k. Field strengths of ∼3 × 10(9) V m(-1) are found to be sufficient to double the tunneling-corrected double proton transfer rate constant at 25 °C. Field strengths of similar orders of magnitudes are encountered in the scanning tunneling microscope (STM), in the microenvironment of a DNA base-pair, in an enzyme active site, and in intense laser radiation fields. It is shown that the net (tunneling corrected) effect of the field on k can be closely fitted to an exponential relationship of the form k = aexp(bE), where a and b are constants and E the electric field strength.

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“…In addition, preclinical studies have demonstrated that the density of CD4+ and CD8+TILs is positively associated with good response after RT, CT and CRT [42]. Furthermore, basic studies of breast and prostate cancer suggest that RT or CT may be more sufficient in immunocompetent mice than immunosuppressive ones [43, 44]. We have found that the addition of CT to RT can not significantly improve OS in the low risk group.…”

Section: Discussionmentioning

confidence: 86%

Identification of a five B cell-associated gene prognostic and predictive signature for advanced glioma patients harboring immunosuppressive subtype preference

Zhang

Wang

et al. 2016

Oncotarget

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High grade gliomas contribute to most brain tumor mortality. A few studies reported that the immune system affected glioma development, and immune biomarkers helped understand the disease and formulate effective immunotherapy for patients. Currently, no B lymphocyte-based prognostic signature was reported in gliomas. By applying 78 B cell lineage-specific genes, we conducted a whole-genome gene expression analysis in 782 high grade gliomas derived from three independent datasets by Cox regression analysis and risk score method for signature identification, and then used Gene Ontology, Gene Set Enrichment Analysis, and other statistical methods for functional annotations of the signature-defined differences. We developed a five B cell-associated gene signature for prognosis of high grade glioma patients, which is independent of clinicopathological and genetic features. The signature identified high risk patients suitable for chemoradiotherapy, whereas low risk patients should rule out chemotherapy with radiotherapy only. We found that tumors of TCGA Mesenchymal subtype and wild type IDH1 were preferentially stratified to the high risk group, which bore strong immunosuppressive microenvironment, while tumors of TCGA Proneural subtype and mutated IDH1 were significantly accumulated to the low risk group, which exhibited less immunosuppressive state. The five B cell-associated gene signature predicts poor survival of high risk patients bearing strong immunosuppression and helps select optimal therapeutic regimens for glioma patients.

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Effective treatment of mouse metastatic prostate cancer by low electric field enhanced chemotherapy

Abstract: Our results suggest that LEFCT-EC is an effective method for the destruction of metastatic prostate tumors.

Cited by 16 publications

References 19 publications

Significance of tumor‐infiltrating lymphocytes before and after neoadjuvant therapy for rectal cancer

Significance of tumor‐infiltrating lymphocytes before and after neoadjuvant therapy for rectal cancer

Effects of external electric fields on double proton transfer kinetics in the formic acid dimer

Identification of a five B cell-associated gene prognostic and predictive signature for advanced glioma patients harboring immunosuppressive subtype preference

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