H MR spectroscopy monitoring of changes in choline peak area and line shape after Gd-contrast administration

Fifteen percent loss in the peak area of choline containing compounds (Cho) was recently observed in ¹H MR spectra of contrast-enhancing tumor at 5–10 min after Gd-contrast administration [Magn. Reson. Med. 37:222–225, 1997]. In this study, chemical shift imaging (CSI, 1500/135 ms PRESS) was used to assess the spectral changes in 47 Gd-enhancing glial brain tumors and metastatic brain tumors measured at 0–5, 5–10, and/or 10–15 min after administration of Gd-contrast. Percent Cho peak area losses measured at these times, 3 ± 3, 12 ± 2, and 14 ± 3 SEM, respectively, coincided with trends of line narrowing and up-field shift of the Cho peak. Significant changes in creatine and N-acetyl acetate signals were not observed. It is concluded that the Gd-induced loss of tumor Cho signal measured after 5 min, typically required for post contrast-MRI and the positioning of the CSI volume on tumor, shows little further change with time, if any.     

Hybrid Nanoreactors: Enabling an Off‐the‐Shelf Strategy for Concurrently Enhanced Chemo‐immunotherapy

Immunosuppressive tumors generally exhibit poor response to immune checkpoint blockade based cancer immunotherapy. Rationally designed hybrid nanoreactors are now presented that have integrated functions as Fenton catalysts and glutathione depletion agents for amplifying the immunogenic cell death and activating immune cells. A simple physical mixture of nanoreactors and chemodrugs in combination with immune checkpoint blockades show synergistically and concurrently enhanced chemo‐immunotherapy efficacy, inhibiting the growth of both treated primary immunosuppressive tumors and untreated distant tumors. The off‐the‐shelf strategy uses tumor antigens generated in situ and avoids cargo loading, and is thus a substantial advance in personalized nanomedicine for clinical translation.     

Promising anticancer drug thapsigargin: A perspective toward the total synthesis

The guaianolide ring containing sesquiterpene thapsigargin is found in the roots and fruits of Mediterranean plant Thapsia garganica L. It is known for its activity as a potent antagonist for Ca²⁺-ATPase (sarco–endoplasmic reticulum Ca²⁺-ATPase) inhibition. Recently, a prodrug mipsagargin is being investigated to target the blood vessel of the cancer cells for the treatment of tumors. The limited natural supply (low isolation and only localized growth (Mediterranean area)) from the natural sources strongly urges for the development of chemical synthetic strategies to access these natural products. This review pertain the various strategies used so far in the thapsigargin’s synthesis, focusing on major contributions in the total synthesis till date.     

Proteomic profiling of pancreatic ductal carcinoma cell lines treated with trichostatin-A

A pancreatic adenocarcinoma cell line (Paca44) was treated with trichostatin-A (TSA), a potent inhibitor of histone deacetylases, in order to evaluate the effect of this drug on protein expression. Master maps of control and treated Paca44 cells were generated by analysis with the PDQuest software. The comparison between such maps showed up- and downregulation of 51 polypeptide chains, out of a total of 700 spots detected by a medium-sensitivity stain, micellar Coomassie Brilliant Blue. Fingerprinting by matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF)-mass spectrometry analysis enabled the identification of 22 of these spots. Among these proteins, of particular interest are the two downregulated proteins nucleophosmin and translationally controlled tumor protein, as well as the upregulated proteins programmed cell death protein 5 (also designated as TFAR19) and stathmin (oncoprotein 18). The modulation of these four proteins is consistent with our observation that TSA is able to inhibit cell growth of Paca44 by causing cell cycle arrest at the G2 phase and apoptotic cell death.     

A mathematical model of combined therapies against cancer using viruses and inhibitors

This paper deals with a procedure for combined therapies against cancer using oncolytic viruses and inhibitors. Replicating genetically modified adenoviruses infect cancer cells, reproduce inside them and eventually cause their death (lysis). As infected cells die, the viruses inside them are released and then proceed to infect other tumor cells. The successful entry of virus into cancer cells is related to the presence of the coxsackie-adenovirus receptor (CAR). Mitogen-activated protein kinase kinase (known as MEK) inhibitors can promote CAR expression, resulting in enhanced adenovirus entry into cancer cells. However, MEK inhibitors can also cause G1 cell-cycle arrest, inhibiting reproduction of the virus. To design an effective synergistic therapy, the promotion of virus infection must be optimally balanced with inhibition of virus production. We introduce a mathematical model to describe the effects of MEK inhibitors and viruses on tumor cells, and use it to explore the reduction of the tumor size that can be achieved by the combined therapies. Furthermore, we find an optimal dose of inhibitor: P _optimal = 1 − μ/δ for a certain initial density of cells (where μ is the removal rate of the dead cells and δ is the death rate of the infected cells). The optimal timing of MEK inhibitors is also numerically studied. This work was supported by the National Natural Science Foundation of China (Grant No. 10571023)     

Numerical simulation of magnetic fluid hyperthermia based on multiphysics coupling and recommendation on preferable treatment conditions

In this study, we established a multiphysics coupling model of magnetic fluid hyperthermia (MFH), using complex magnetic permeability to solve the magnetic losses of magnetic nanoparticles (MNPs). The experiments were performed to verify the validity of numerical coupling method. The optimal treatment time (OTT) was regarded as the time required for the lowest temperature point of the tumor to attain the damage criteria. The OTT increased by about 42 s as the tumor radius increased by 1 cm, and decreased by 10 s for the increase in MNP dose per gram of tumor by 1 mg. To achieve cost-effective therapies under moderate treatment conditions, the preferable ranges of external magnetic field intensity H₀ and frequency f, MNP radius R and volume fraction $?$ are 3–11 kA/m, 200–500 kHz, 8–10 nm, and 5%–10%, respectively. It is greatly encouraged to adopt the combination of higher H₀ (8–11 kA/m) and lower f (200–300 kHz), and the conjunction of higher R and $?$. There was a slight thermal damage to normal tissues due to eddy current loss. In conclusion, MFH can provide an excellent therapeutic effect for deep tumors.     

Diet and gastrointestinal signal on T1-weighted magnetic resonance imaging of mice

In magnetic resonance (MR) imaging of small animals, the gastrointestinal contents may give rise to intense signals on T1-weighted images. The aim of this study was to determine the optimal dietary preparation to reduce gastrointestinal signals in mice and to evaluate the usefulness of this approach. Images of the mouse trunk were obtained using a T1-weighted, three-dimensional fast low-angle shot sequence under various dietary conditions and were compared with respect to the gastrointestinal signals and image quality. The dietary preparation studied included giving alternative diets for 24 h, intestinal cleansing, and 6-h fasting. Mice with and without dietary preparation underwent MR lymphography using gadofluorine 8, and the visualization of abdominal lymph nodes was compared. In the absence of dietary preparation, hyperintense areas were conspicuous in the gastrointestinal system, whereas on the images taken from mice fed potato or sweet potato for 24 h before imaging, gastrointestinal hyperintensity was less prominent. This preparation also reduced artifactual signals and resulted in higher-quality images of the kidneys. Intestinal cleansing, which consisted of 24-h fasting and laxative intake, did not reduce the gastrointestinal signals and caused signal changes that were indicative of fatty liver development. Some of the abdominal lymph nodes of the mice that did not receive dietary preparation were visualized on MR lymphography source images but not on maximum intensity projection (MIP) images. In contrast, on the MIP images of mice fed potato, all the lymph nodes delineated on the source images were successfully visualized. In conclusion, feeding mice potato or sweet potato for 24 h before MR imaging reduces the gastrointestinal signals and image degradation due to artifacts. Appropriate dietary preparations facilitate the display of target structures on MIP images and are expected to enhance the capabilities of small animal MR imaging.     

Well-posedness and stability for an elliptic-parabolic free boundary problem modeling the growth of multi-layer tumors

In this paper we study a free boundary problem modeling the growth of multi-layer tumors. This free boundary problem contains one parabolic equation and one elliptic equation, defined on an unbounded domain in R2 of the form 0 〈 y 〈p（x,t）, where p（x,t） is an unknown function. Unlike previous works on this tumor model where unknown functions are assumed to be periodic and only elliptic equations are evolved in the model, in this paper we consider the case where unknown functions are not periodic functions and both elliptic and parabolic equations appear in the model. It turns out that this problem is more difficult to analyze rigorously. We first prove that this problem is locally well-posed in little H61der spaces. Next we investigate asymptotic behavior of the solution. By using the principle of linearized stability, we prove that if the surface tension coefficient y is larger than a threshold value y〉0, then the unique flat equilibrium is asymptotically stable provided that the constant c representing the ratio between the nutrient diffusion time and the tumor-cell doubling time is sufficiently small.