Independent validation of CT radiomics models in colorectal liver metastases: predicting local tumour progression after ablation.

Objectives: Independent internal and external validation of three previously published CT-based radiomics models to predict local tumor progression (LTP) after thermal ablation of colorectal liver metastases (CRLM).

Materials And Methods: Patients with CRLM treated with thermal ablation were collected from two institutions to collect a new independent internal and external validation cohort. Ablation zones (AZ) were delineated on portal venous phase CT 2-8 weeks post-ablation.

Imaging-calculated splenic volume is associated with response in melanoma patients treated with immunotherapy.

Predicting the roughly 50% of melanoma patients that will respond to immunotherapy is challenging. We tested if splenic volume could be a predictive biomarker. Splenic volume was measured by a semiautomated commercial software tool in pre- and post-treatment PET/CT, CT or MRI in 50 melanoma patients treated with immune checkpoint inhibitors.

Targeting immunosuppressive macrophages overcomes PARP inhibitor resistance in BRCA1-associated triple-negative breast cancer.

Despite objective responses to PARP inhibition and improvements in progression-free survival compared to standard chemotherapy in patients with BRCA-associated triple-negative breast cancer (TNBC), benefits are transitory. Using high dimensional single-cell profiling of human TNBC, here we demonstrate that macrophages are the predominant infiltrating immune cell type in BRCA-associated TNBC. Through multi-omics profiling we show that PARP inhibitors enhance both anti- and pro-tumor features of macrophages through glucose and lipid metabolic reprogramming driven by the sterol regulatory element-binding protein 1 (SREBP-1) pathway.

Inactivation of the Prolyl Isomerase Pin1 Sensitizes BRCA1-Proficient Breast Cancer to PARP Inhibition.

PARP inhibitor monotherapies are effective to treat patients with breast, ovary, prostate, and pancreatic cancer with BRCA1 mutations, but not to the much more frequent BRCA wild-type cancers. Searching for strategies that would extend the use of PARP inhibitors to BRCA1-proficient tumors, we found that the stability of BRCA1 protein following ionizing radiation (IR) is maintained by postphosphorylational prolyl-isomerization adjacent to Ser1191 of BRCA1, catalyzed by prolyl-isomerase Pin1. Extinction of Pin1 decreased homologous recombination (HR) to the level of BRCA1-deficient cells.

Destruction of a Microtubule-Bound MYC Reservoir during Mitosis Contributes to Vincristine's Anticancer Activity.

Tightly regulated activity of the transcription factor MYC is essential for orderly cell proliferation. Upon deregulation, MYC elicits and promotes cancer progression. Proteasomal degradation is an essential element of MYC regulation, initiated by phosphorylation at Serine62 (Ser62) of the MB1 region.

Serial-omics of P53-/-, Brca1-/- Mouse Breast Tumor and Normal Mammary Gland.

This study demonstrates a liquid-liquid extraction for the sequential tandem mass spectrometry (LC-MS/MS) analysis of non-polar lipids, polar metabolites, proteins and phosphorylation sites from a single piece of tissue. Extraction of 10 mg BRCA-/-, p53-/- breast tumor tissue or normal mammary gland tissue with methyl-tert-butyl ether (MTBE) results in three phases: an upper non-polar phase containing 1,382 lipids, a lower polar phase with 805 metabolites and a precipitated protein pellet with 4,792 proteins with 1,072 phosphorylation sites. Comparative analysis revealed an activated AKT-mTOR pathway in tumors.

Genomic characteristics of trastuzumab-resistant Her2-positive metastatic breast cancer.

Purpose: Resistance to trastuzumab therapy is linked to phosphoinositol 3-kinase (PI3K) pathway activation. One key downstream effector and regulator of this pathway is the mechanistic target of rapamycin (mTOR). In 2011, a phase I/II study evaluated the combination of trastuzumab and everolimus (a mTOR inhibitor) for treatment of Her2-positive metastatic breast cancer (MBC) for patients who had progressed on trastuzumab-based therapy.

Neurocysticercotic Calcifications and Hippocampal Sclerosis: A Case-Control Study.

Objective: The exact role of calcified neurocysticercotic lesions (CNLs) in epilepsy is yet unknown and controversial. Although the relationship between CNLs, epilepsy and mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) has already been addressed, to our knowledge, no study has actually provided strong statistical evidence, nor reported the ODDS ratio for these associations. Therefore, we designed this case-control study to assess the likelihood of having MTLE-HS versus other forms of epilepsy in the presence of CNLs.