DSTYK inhibition increases the sensitivity of lung cancer cells to T cell-mediated cytotoxicity.

Lung cancer remains the leading cause of cancer-related death worldwide. We identify DSTYK, a dual serine/threonine and tyrosine non-receptor protein kinase, as a novel actionable target altered in non-small cell lung cancer (NSCLC). We also show DSTYK's association with a lower overall survival (OS) and poorer progression-free survival (PFS) in multiple patient cohorts.

A Fibrosis Biomarker Early Predicts Cardiotoxicity Due to Anthracycline-Based Breast Cancer Chemotherapy.

Anthracycline-based cancer chemotherapy (ACC) causes myocardial fibrosis, a lesion contributing to left ventricular dysfunction (LVD). We investigated whether the procollagen-derived type-I C-terminal-propeptide (PICP): (1) associates with subclinical LVD (sLVD) at 3-months after ACC (3m-post-ACC); (2) predicts cardiotoxicity 1-year after ACC (12m-post-ACC) in breast cancer patients (BC-patients); and (3) associates with LVD in ACC-induced heart failure patients (ACC-HF-patients). Echocardiography, serum PICP and biomarkers of cardiomyocyte damage were assessed in two independent cohorts of BC-patients: CUN (n = 87) at baseline, post-ACC, and 3m and 12m (n = 65)-post-ACC; and HULAFE (n = 70) at baseline, 3m and 12m-post-ACC.

Genomic characterization of individuals presenting extreme phenotypes of high and low risk to develop tobacco-induced lung cancer.

Single nucleotide polymorphisms (SNPs) may modulate individual susceptibility to carcinogens. We designed a genome-wide association study to characterize individuals presenting extreme phenotypes of high and low risk to develop tobacco-induced non-small cell lung cancer (NSCLC), and we validated our results. We hypothesized that this strategy would enrich the frequencies of the alleles that contribute to the observed traits.

The inhibitor of differentiation-1 (Id1) enables lung cancer liver colonization through activation of an EMT program in tumor cells and establishment of the pre-metastatic niche.

Id1 promotes carcinogenesis and metastasis, and predicts prognosis of non-small cell lung cancer (NSCLC)-adenocarcionoma patients. We hypothesized that Id1 may play a critical role in lung cancer colonization of the liver by affecting both tumor cells and the microenvironment. Depleted levels of Id1 in LLC (Lewis lung carcinoma cells, LLC shId1) significantly reduced cell proliferation and migration in vitro.

Bringing Model-Based Prediction to Oncology Clinical Practice: A Review of Pharmacometrics Principles and Applications.

Unlabelled: Despite much investment and progress, oncology is still an area with significant unmet medical needs, with new therapies and more effective use of current therapies needed. The emergent field of pharmacometrics combines principles from pharmacology (pharmacokinetics [PK] and pharmacodynamics [PD]), statistics, and computational modeling to support drug development and optimize the use of already marketed drugs. Although it has gained a role within drug development, its use in clinical practice remains scarce.

Early Prediction of Disease Progression in Small Cell Lung Cancer: Toward Model-Based Personalized Medicine in Oncology.

Predictive biomarkers can play a key role in individualized disease monitoring. Unfortunately, the use of biomarkers in clinical settings has thus far been limited. We have previously shown that mechanism-based pharmacokinetic/pharmacodynamic modeling enables integration of nonvalidated biomarker data to provide predictive model-based biomarkers for response classification.

Role of [¹⁸F]FDG PET in prediction of KRAS and EGFR mutation status in patients with advanced non-small-cell lung cancer.

Purpose: The tumour molecular profile predicts the activity of epidermal growth factor receptor (EGFR) inhibitors in non-small-cell lung cancer (NSCLC). However, tissue availability and tumour heterogeneity limit its assessment. We evaluated whether [(18)F]FDG PET might help predict KRAS and EFGR mutation status in NSCLC.

A population pharmacodynamic model for lactate dehydrogenase and neuron specific enolase to predict tumor progression in small cell lung cancer patients.

The development of individualized therapies poses a major challenge in oncology. Significant hurdles to overcome include better disease monitoring and early prediction of clinical outcome. Current clinical practice consists of using Response Evaluation Criteria in Solid Tumors (RECIST) to categorize response to treatment.

Randomized pharmacokinetic study comparing subcutaneous and intravenous palonosetron in cancer patients treated with platinum based chemotherapy.

Background: Palonosetron is a potent second generation 5- hydroxytryptamine-3 selective antagonist which can be administered by either intravenous (IV) or oral routes, but subcutaneous (SC) administration of palonosetron has never been studied, even though it could have useful clinical applications. In this study, we evaluate the bioavailability of SC palonosetron.

Patients And Methods: Patients treated with platinum-based chemotherapy were randomized to receive SC or IV palonosetron, followed by the alternative route in a crossover manner, during the first two cycles of chemotherapy.

Identification of tissue microRNAs predictive of sunitinib activity in patients with metastatic renal cell carcinoma.

Purpose: To identify tissue microRNAs predictive of sunitinib activity in patients with metastatic renal-cell-carcinoma (MRCC) and to evaluate in vitro their mechanism of action in sunitinib resistance.

Methods: We screened 673 microRNAs using TaqMan Low-density-Arrays (TLDAs) in tumors from MRCC patients with extreme phenotypes of marked efficacy and resistance to sunitinib, selected from an identification cohort (n = 41). The most relevant differentially expressed microRNAs were selected using bioinformatics-based target prediction analysis and quantified by qRT-PCR in tumors from patients presenting similar phenotypes selected from an independent cohort (n = 101).

Id1 and Id3 co-expression correlates with clinical outcome in stage III-N2 non-small cell lung cancer patients treated with definitive chemoradiotherapy.

Background: Inhibitor of DNA binding 1 (Id1) and 3 (Id3) genes have been related with the inhibition of cell differentiation, cell growth promotion and tumor metastasis. Recently, Id1 has been identified as an independent prognostic factor in patients with lung adenocarcinoma, regardless of the stage. Furthermore, Id1 may confer resistance to treatment (both, radiotherapy and chemotherapy).

Hypomagnesemia as a possible explanation behind episodes of severe pain in cancer patients receiving palliative care.

Within an oncology setting, certain chemotherapy drugs, such as cisplatin, may lead to magnesium loss causing nephropathy. Neurological and cardiovascular symptoms caused by hypomagnesaemia are well known. The relationship between serious hypomagnesemia and severe pain is not well documented but nevertheless, when faced with unexplained episodes of pain which do not respond to powerful analgesics, it is important to review blood magnesium levels.

The multimodal management of locally advanced N2 non-small cell lung cancer: is there a role for surgical resection? A single institution's experience.

Background: The management of operable locally advanced N2 non-small cell lung cancer (NSCLC) is a controversial topic. Concurrent chemoradiation (CT-RT) is considered the standard of care for inoperable or unresectable patients, but the role of trimodality treatment remains controversial. We present our institution's experience with the management of stage III (N2) NSCLC patients, analyzing whether the addition of surgery improves survival when compared with definitive CT-RT alone.

Concomitant cisplatin, paclitaxel, and hyperfractionated radiotherapy in locally advanced head and neck cancer: comparison of two different schedules.

Purpose: To determine feasibility and efficacy of concurrent paclitaxel and cisplatin with definitive hyperfractionated radiotherapy (HFRT) in locally advanced head-and-neck squamous cell carcinoma (HNSCC).

Patients And Methods: Forty-two patients stages III to IV head-and-neck squamous cell carcinoma were enrolled in 2 consecutive prospective trials from August 1998 to January 2006. In study 1, 16 patients received HFRT in 2 courses of 39.

An imbalance in Akt/mTOR is involved in the apoptotic and acantholytic processes in a mouse model of pemphigus vulgaris.

Pemphigus vulgaris (PV) is an autoimmune blistering disease characterized by the presence of IgG autoantibodies against Dsg3. Our aim was to investigate the molecular events implicated in the development and localization of apoptosis and acantholysis in PV. We used a passive transfer mouse model together with immunohistochemical (IHC) techniques and the TUNEL assay, with quantification analysis in the basal layer of the epidermis.

Adult onset Still's disease after first cycle of pemetrexed and gemcitabine for non-small cell lung cancer.

Pemetrexed is a multitargeted antifolate approved for the second-line treatment of locally advanced or metastatic non-small cell lung cancer. The combination of pemetrexed with gemcitabine has been studied in several clinical trials showing a promising antitumor activity with a mild toxicity profile. We present the case of a patient who experienced fever, arthralgia, skin rash and high serum ferritin levels after first cycle of this chemotherapy combination, compatible with an adult onset Still's disease.

Dosimetric analysis of the patterns of local failure observed in patients with locally advanced non-small cell lung cancer treated with neoadjuvant chemotherapy and concurrent conformal (3D-CRT) chemoradiation.

Purpose: Three-dimensional conformal radiation therapy (3D-CRT) represents an advance in the better delineation of the target contours and more accurate dose distributions. The purpose of this study was to identify local control prognostic factors in patients with locally advanced non-small cell lung cancer (LA-NSCLC) treated with 3D-CRT.

Material And Methods: Between April 1995 and March 2002, 65 patients (NSCLC stage IIIA: 20%, IIIB: 77%) were treated with cisplatin-based induction and concurrent chemotherapy chemotherapy and hyperfractioned 3D-CRT (1.

CT-guided permanent brachytherapy for patients with medically inoperable early-stage non-small cell lung cancer (NSCLC).

Seven patients with early stage T1N0M0 NSCLC who had medical contraindications for surgical resection were treated with CT-guided percutaneous implantation of (103)Pd or (125)I seeds. After the procedure, two patients developed pneumothorax and hemo/pneumothorax that was managed with aspirative drainage. One patient developed a focal pneumonitis 3 months after the procedure.

Activity of gefitinib in central nervous system metastases in patients with non-small-cell lung cancer: two case reports and a review of the literature.

Gefitinib is the first inhibitor of the epidermal growth factor receptor that has shown activity in non-small-cell lung cancer (NSCLC), but its potential value in the treatment of central nervous system (CNS) metastases has been rarely assessed. We report 2 cases of patients with CNS metastases responding to gefitinib and a review of all the cases previously published in the literature. Computerized and manual searches were performed to identify reports of patients with NSCLC with CNS metastases treated with gefitinib.

Assessment of the value of confirming responses in clinical trials in oncology.

The requirement for a second assessment to confirm initial tumour response is required by all response guidelines. Its rationale, however, is not clear. We have conducted this study to compare validity of response rate assessment determined with and without secondary confirmation.

Percutaneous CT-guided 103Pd implantation for the medically inoperable patient with T1N0M0 non-small cell lung cancer: a case report.

Three patients with early-stage T1N0M0 non-small cell lung cancer (NSCLC) who had medical contraindications for standard surgical resection were treated with CT-guided percutaneous implantation of (103)Pd seeds. The technique was proven safe in this small subset of patients without any complications related to the procedure or during short-term follow-up.

Paclitaxel, cisplatin, and vinorelbine combination chemotherapy in metastatic non-small-cell lung cancer.

Vinorelbine-cisplatin combination chemotherapy is a standard approach for the treatment of advanced non-small-cell lung cancer (NSCLC). The addition of paclitaxel as a third therapeutic agent seems promising. The aim of the present study was to evaluate the activity and toxicity of this new regimen.