Optimizing interstitial photodynamic therapy with custom cylindrical diffusers

Interstitial photodynamic therapy (iPDT) has shown promise recently as a minimally invasive cancer treatment, partially due to the development of non‐toxic photosensitizers in the absence of activation light. However, a major challenge in iPDT is the pre‐treatment planning process that specifies the number of diffusers needed, along with their positions and allocated powers, to confine the light distribution to the target volume as much as possible. In this work, a new power allocation algorithm for cylindrical light diffusers including those that can produce customized longitudinal (tailored) emission profiles is introduced. The proposed formulation is convex to guarantee the minimum over‐dose possible on the surrounding organs‐at‐risk. The impact of varying the diffuser lengths and penetration angles on the quality of the plan is evaluated. The results of this study are demonstrated for different photosensitizers activated at different wavelengths and simulated on virtual tumors modeling virtual glioblastoma multiforme cases. Results show that manufacturable cylindrical diffusers with tailored emission profiles can significantly outperform those with conventional flat profiles with an average damage reduction on white matter of 15% to 55% and on gray matter of 23% to 58%.      

Tomographic molecular imaging and 3D quantification within adult mouse organs

A convenient technology to quantify three-dimensional (3D) morphological features would have widespread applications in biomedical research. Based on combined improvements in sample preparation, tomographic imaging and computational processing, we present a procedure for high-resolution 3D quantification of structures within intact adult mouse organs. Using the nonobese diabetic (NOD) mouse model, we demonstrate a correlation between total islet beta-cell volume and the onset of type-1 diabetes.     

MicroRNA in leukemia: Tumor suppressors and oncogenes with prognostic potential

Leukemia is known as a progressive malignant disease, which destroys the blood-forming organs and results in adverse effects on the proliferation and development of leukocytes and their precursors in the blood and bone marrow. There are four main classes of leukemia including acute leukemia, chronic leukemia, myelogenous leukemia, and lymphocytic leukemia. Given that a variety of internal and external factors could be associated with the initiation and progression of different types of leukemia. One of the important factors is epigenetic regulators such as microRNAs (miRNAs) and long noncoding RNAs (ncRNA). MiRNAs are short ncRNAs which act as tumor suppressor (i.e., miR-15, miR-16, let-7, and miR-127) or oncogene (i.e., miR-155, miR-17-92, miR-21, miR-125b, miR-93, miR-143-p3, miR-196b, and miR-223) in leukemia. It has been shown that deregulation of these molecules are associated with the initiation and progression of leukemia. Hence, miRNAs could be used as potential therapeutic candidates in the treatment of patients with leukemia. Moreover, increasing evidence revealed that miRNAs could be used as diagnostic and prognostic biomarkers in monitoring patients in early stages of disease or after received chemotherapy regimen. It seems that identification and development of new miRNAs could pave to the way to the development new therapeutic platforms for patients with leukemia. Here, we summarized various miRNAs as tumor suppressor and oncogene which could be introduced as therapeutic targets in treatment of leukemia.     

PNU-74654 enhances the antiproliferative effects of 5-FU in breast cancer and antagonizes thrombin-induced cell growth via the Wnt pathway

The Wnt/β-catenin pathway is one of the most common pathways dysregulated in breast cancer, and may, therefore, be a potential-therapeutic target. We have investigated the effects of PNU-74654 in breast cancer, as a Wnt/β-catenin inhibitor, either alone or in combination with fluorouracil (5-FU). PNU-74654 suppressed cell growth at an IC ₅₀ of 122 ± 0.4 μmol/L and synergistically enhanced the antiproliferative activity of gemcitabine by modulating the Wnt pathway. Using a 3D cell culture model, we found that the PNU-74654 caused tumor shrinkage. It reduced the migration of MCF-7 cells (by an 18% reduction in invasive behavior) after the treatment with PNU-74654 through perturbation of E-cadherin and MMP3/9. PNU-74654/5-FU combination enhanced the percentages of cells in S-phase and significantly increased apoptosis. Moreover, our data showed that this agent was able to inhibit the growth of tumor in a xenograft model, although this effect was more pronounced in the animals treated with PNU-74654 plus 5-FU. These data show the ability of PNU-74654 to specifically target Wnt pathway, interfere with cell proliferation, induce-apoptosis, reduce-migration, and synergistically interact with 5-FU, supporting further studies on this novel therapeutic-approach for breast cancer.