Nanoparticle albumin-bound (nab)-paclitaxel (Abraxane) is an albumin-bound 130-nm particle form of paclitaxel that demonstrated higher efficacy and was well tolerated compared with solvent-based paclitaxel (Taxol) and docetaxel (Taxotere) in clinical trials for metastatic breast cancer. Nab-paclitaxel enhances tumor targeting through gp60 and caveolae-mediated endothelial transcytosis and the association with the albumin-binding protein SPARC (secreted protein, acidic and rich in cysteine) in the tumor microenvironment. The overexpression of human epidermal growth factor receptor-2 (HER2) in breast cancer has been shown to correlate with resistance to paclitaxel. To evaluate the importance of HER2 and SPARC status in determining the relative efficacy of nab-paclitaxel compared with polysorbate-based docetaxel, nude mice bearing six different human tumor xenografts were treated with nab-paclitaxel (MX-1: 15 mg/kg, once a week for 3 weeks; LX-1, MDA-MB-231/HER2+, PC3, and HT29: 50 and 120 mg/kg, every 4 days three times ; MDA-MB-231: 120 and 180 mg/kg, every 4 days three times) and polysorbate-based docetaxel (15 mg/kg). HER2 and SPARC status were analyzed by RT-PCR and immunohistochemical staining. MDA-MB-231 and MX-1 breast and LX-1 lung cancers were HER2 negative and low in SPARC expression. Nab-paclitaxel at submaximum-tolerated dosage was significantly more effective than polysorbate-based docetaxel at its maximum-tolerated dosage in these three HER2-negative tumors. The HER2-positive tumors had variable SPARC expression, with MDA-MB-231/HER2+

Background Aspiration pneumonia represents an under-reported complication of chemoradiotherapy in head-and-neck cancer. This study evaluated the incidence, risk factors, and mortality of aspiration pneumonia in a large cohort of head-and-neck cancer patients treated with concurrent chemoradiotherapy. Methods Patients with head-and-neck cancer diagnosed between 2000 and 2009 were identified from the SEER-Medicare database. Aspiration pneumonia was identified from Medicare billing claims. The cumulative incidence, risk factors, and survival after aspiration pneumonia were estimated and compared to a non-cancer population. Results Of 3,513 head-and-neck cancer patients, 801 patients developed aspiration pneumonia at a median time of 5 months after initiating treatment. The 1- and 5-year cumulative incidence of aspiration pneumonia was 15.8% and 23.8% for head-and-neck cancer patients and 3.6% and 8.7% for non-cancer controls, respectively. Among cancer patients multivariate analysis identified independent risk factors (p<0.05) for aspiration pneumonia including hypopharyngeal and nasopharyngeal tumors, male gender, older age, increased comorbidity, no surgery prior to radiation, and care received at a teaching hospital. Among cancer patients who experienced aspiration pneumonia, 674 (84%) were hospitalized of which 301 (45%) were admitted to an intensive care unit. Thirty-day mortality after hospitalization for aspiration pneumonia was 32.5%. Aspiration pneumonia was associated with a 42% increased risk of death (HR=1.42, p<0.001) after controlling for confounders. Conclusions This study found that nearly one-quarter of elderly patients will develop aspiration pneumonia within 5 years of chemoradiotherapy for head-and-neck cancer. A better understanding of mitigating factors will help identify patients at risk for this potentially lethal complication.

MicroRNAs are gene regulators that work through a posttranscriptional repression mechanism. Dysregulation of microRNA expression could lead to a variety of disorders, in particular, human cancer, and has also been implicated in antihormone therapy resistance. However, little is known whether microRNAs have a role in estrogen-independent growth, leading to tamoxifen resistance in estrogen receptor (ER)-positive tumors. In this study, we use an in vivo selection system against a microRNA library using the MCF-7 model and demonstrate that miR-101 promotes estrogen-independent growth and causes the upregulation of phosphorylated Akt (pAkt) without impacting the ER level or activity. Importantly, although miR-101 suppresses cell growth in normal estradiol (E2)-containing medium, it promotes cell growth in E2-free medium. Moreover, estrogen deprivation greatly enhances miR-101-mediated Akt activation. Finally, we show that MAGI-2 (membrane-associated guanylate kinase), a scaffold protein required for PTEN (phosphatase and tensin homolog) activity, is a direct target for miR-101; suppression of MAGI-2 by miR-101 reduces PTEN activity, leading to Akt activation. Taken together, these results not only establish a role for miR-101 in estrogen-independent signaling but also provide a mechanistic link between miR-101 and Akt activation.

Compared with standard modeling approaches, GCE models improve stratification of elderly patients with cancer according to their risk of dying from cancer relative to overall mortality.