Philadelphia University + Thomas Jefferson University


Highlighted Publications

Simone, B.A., Dan, T., Palagani, A., Jin, L., Han, S.Y., Wright, C., Savage, J.E., Gitman, R., Lim, M.K., Palazzo, J., Mehta, M.P., Simone, N.L. 2016, “Caloric restriction coupled with radiation decreases metastatic burden in triple negative breast cancer”, Cell Cycle, Volume 15, Issue 17, Pages 2265-2274.

We wanted to determine if using a caloric restriction (CR) as a systemic therapy, combined with radiation therapy (IR) to the primary tumor may impact metastatic disease. An orthotopic mouse model using a highly metastatic, luciferase-tagged triple negative breast cancer (TNBC) model was used. The mice was then treated with CR-only, IR-only and a combination of the two. Molecular analysis was conducted showing that CR decreases proliferation, increases apoptosis, increases survival and globally down regulates the IGF-1R signaling pathway. CR decreased metastatic burden and therefore may complement cytotoxic therapies being used in the clinical setting for metastatic disease.

Jin, L., Lim, M., Zhao, S., Sano, Y., Simone, B.A., Savage, J.E., Wickstrom, E., Camphausen, K., Pestell, R.G., Simone, N.L. 2014, “The metastatic potential of triple-negative breast cancer is decreased via caloric restriction-mediated reduction of the miR-17~92 cluster”, Breast Cancer Research and Treatment, Volume 146, Issue 1, Pages 41-50.

In this study, we found that 3 miRs in the miR-17~92 cluster is down regulated when caloric restriction (CR) is coupled with ionizing radiation (IR) in triple-negative breast cancer (TNBC) models. Four potential targets of the miR cluster related to the extracellular matrix (ECM) were analyzed through cDNA arrays and in silico, which were then confirmed through luciferase assays. Functionally, we demonstrated that CR decreases the metastatic potential of cells signifying the importance of the ECM.

Saleh, A.D., Simone, B.A., Palazzo, J., Savage, J.E., Sano, Y., Dan, T., Jin, L., Champ, C., Zhao, S., Lim, M., Sotgia, F., Camphausen, K., Pestell, R.G., Mitchell, J.B., Lisanti, M.P., Simone, N.L. 2013, “Caloric restriction augments radiation efficacy in breast cancer”, Cell Cycle, Volume 12, Issue 12, Pages 1955-1963.

Dietary modifications such as caloric restriction (CR) has shown to decrease tumor initiation and progression so we sought to determine if nutrient restriction could be used as a novel therapeutic intervention to improve cytotoxic therapies such as radiation (IR) and affect the molecular profiles of triple-negative breast cancer (TNBC). The most effective diet modification was a 30% reduction of the total daily caloric intake and that tumors treated with both CR and IR showed less proliferation and more apoptosis. We were able to confirm that the IGF-1R pathway (IGF-1R, IRS, PIK3ca and mTOR) became down-regulated.

Ørom, U.A., Lim, M.K., Savage, J.E., Jin, L., Saleh, A.D., Lisanti, M.P., Simone, N.L. 2012, “MicroRNA-203 regulates caveolin-1 in breast tissue during caloric restriction”, Cell Cycle, Volume 11, Issue 7, Pages 1291-1295.

We characterize the microRNA expression in mouse breast tissue before and after caloric restriction, reporting several changes in the microRNA expression profile. miR-203 is found to be highly induced by caloric restriction, and we demonstrate that caveolin-1 as well as p63 are direct targets of miR-203 in vivo during caloric restriction. In conclusion, we show that the microRNA response induced by caloric restriction can regulate important factors in processes such as longevity and aging and is an integral and important component of the cellular response to caloric restriction.


Recent Publications

Onco-metabolism: defining the prognostic significance of obesity and diabetes in women with brain metastases from breast cancer

Discrepancies between biomarkers of primary breast cancer and subsequent brain metastases: an international multicenter study

NRG Oncology–Radiation Therapy Oncology Group Study 1014: 1-Year Toxicity Report From a Phase 2 Study of Repeat Breast-Preserving Surgery and 3-Dimensional Conformal Partial-Breast Reirradiation for In-Breast Recurrence

Clinical-pathological features and treatment modalities associated with recurrence in DCIS and micro-invasive carcinoma: Who to treat more and who to treat less

Caloric restriction coupled with radiation decreases metastatic burden in triple negative breast cancer

Obesity and tumor growth: Inflammation, immunity, and the role of a ketogenic diet

Phase I trial of panobinostat and fractionated stereotactic re-irradiation therapy for recurrent high grade gliomas

A single activity with a practice quality improvement project for faculty and a quality improvement project for residents

Not so fast: Dietary restriction improves chemotherapy-related toxicity

Modeled risk of ischemic heart disease following left breast irradiation with deep inspiration breath hold

Active Breathing Coordinator reduces radiation dose to the heart and preserves local control in patients with left breast cancer: Report of a prospective trial

MicroRNA alterations driving acute and late stages of radiation-induced fibrosis in a murine skin model

What benefits could caloric restriction bring to cancer patients?

MicroRNAs: The short link between cancer and RT-induced DNA damage response

Intraoperative radiotherapy for breast cancer: The lasting effects of a fleeting treatment

MicroRNA expression altered by diet: Can food be medicinal?

The metastatic potential of triple-negative breast cancer is decreased via caloric restriction-mediated reduction of the miR-17~92 cluster

CD44 is prognostic for overall survival in the NCI randomized trial on breast conservation with 25 year follow-up

RE: Calorie or carbohydrate restriction? The ketogenic diet as another option for supportive cancer treatment

Selectively starving cancer cells through dietary manipulation: Methods and clinical implications