Transport of molecules across tumor vasculature

The vascular-extravascular exchange of fluid and solute molecules in a tissue is determined by three transport parameters (vascular permeability, P, hydraulic conductivity, L_p, and reflection coefficient, ); the surface area for exchange, A; and the transluminal concentration and pressure gradients. The transport parameters and the exchange area for a given molecule are governed by the structure of the vessel wall. In general, tumor vessels have wide interendothelial junctions; large number of fenestrae and transendothelial channels formed by vesicles; and discontinuous or absent basement membrane. While these factors favor movement of molecules across tumor vessels, high interstitial pressure and low microvascular pressure may retard extravasation of molecules and cells, especially in large tumors. These characteristics of the transvascular transport have significant implications in tumor growth, metastasis, detection and treatment.     

Prostaglandin E1-induced Catalepsy in the Rat: Role of Putative Neutrotransmitters

Prostaglandin E₁ (PGE₁) produced dose-related catalepsy in rats when administered intracerebroventricularly. PGE₁ induced catalepsy was significantly inhibited after pretreatment with pharmacological agents known to attenuate central serotonergic and cholinergic activity. It was also inhibited by PGF₂ and naloxone. On the contrary, treatments enhancing central dopaminergic activity also reduced the cataleptic effect of PGE₁. The results suggest that PGE₁ induces catalepsy in rats by modulating activity of central neurotransmitters.     

Anticancer Mechanism of Curcumin on Human Glioblastoma

Glioblastoma (GBM) is the most malignant brain tumor and accounts for most adult brain tumors. Current available treatment options for GBM are multimodal, which include surgical resection, radiation, and chemotherapy. Despite the significant advances in diagnostic and therapeutic approaches, GBM remains largely resistant to treatment, with a poor median survival rate between 12 and 18 months. With increasing drug resistance, the introduction of phytochemicals into current GBM treatment has become a potential strategy to combat GBM. Phytochemicals possess multifarious bioactivities with multitarget sites and comparatively marginal toxicity. Among them, curcumin is the most studied compound described as a potential anticancer agent due to its multi-targeted signaling/molecular pathways properties. Curcumin possesses the ability to modulate the core pathways involved in GBM cell proliferation, apoptosis, cell cycle arrest, autophagy, paraptosis, oxidative stress, and tumor cell motility. This review discusses curcumin’s anticancer mechanism through modulation of Rb, p53, MAPK, P13K/Akt, JAK/STAT, Shh, and NF-κB pathways, which are commonly involved and dysregulated in preclinical and clinical GBM models. In addition, limitation issues such as bioavailability, pharmacokinetics perspectives strategies, and clinical trials were discussed.     

Alterations in Breast Cancer Biomarkers Following Neoadjuvant Therapy

Annals of Surgical Oncology - Biomarker changes in patients with residual disease (RD) after neoadjuvant systemic therapy (NAT) have unclear consequences. This study examined the prevalence of...     

Comparison of multiple oncotype DX® from the same patient

For women with breast cancer in whom multiple Oncotype DX^® Recurrence Scores (RS) are obtained, RS concordance utilizing current NCCN recommendations has not been evaluated. Patients with two or more RS were identified. RS were stratified by NCCN guidelines and compared for concordance. Twenty-four patients were evaluated. RS concordance varied by tumor type: 100% in the same tumor, 91.7% in multiple ipsilateral tumors, 71.4% in contralateral tumors, and 66.7% in in-breast recurrent tumors. RS concordance for multiple assays in the same patient is not high enough to omit Oncotype DX^® testing for each tumor.     

Kidney transplant program waitlisting rate as a metric to assess transplant access

Kidney transplant program performance in the United States is commonly measured by posttransplant outcomes. Inclusion of pretransplant measures could provide a more comprehensive assessment of transplant program performance and necessary information for patient decision-making. In this study, we propose a new metric, the waitlisting rate, defined as the ratio of patients who are waitlisted in a center relative to the person-years referred for evaluation to a program. Furthermore, we standardize the waitlisting rate relative to the state average in Georgia, North Carolina, and South Carolina. The new metric was used as a proof-of-concept to assess transplant-program access compared to the existing transplant rate metric. The study cohorts were defined by linking 2017 United States Renal Data System (USRDS) data with transplant-program referral data from the Southeastern United States between January 1, 2012 and December 31, 2016. Waitlisting rate varied across the 9 Southeastern transplant programs, ranging from 10 to 22 events per 100 patient-years, whereas the program-specific waitlisting rate ratio ranged between 0.76 and 1.33. Program-specific waitlisting rate ratio was uncorrelated with the transplant rate ratio (r = −.15, 95% CI, −0.83 to 0.57). Findings warrant collection of national data on early transplant steps, such as referral, for a more comprehensive assessment of transplant program performance and pretransplant access.