Rapid detection and destruction of squamous cell carcinoma of the head and neck by nano‐quadrapeutics

Survival and quality of life remain poor for patients with head and neck squamous cell carcinoma (HNSCC) that cannot be fully resected safely, and form therapy‐resistant residual and recurrent tumors. We report novel cell‐level technology, quadrapeutics. Quadrapeutics converts surgery, drug, and radiation therapies into on‐demand microtreatment that unites the diagnosis and treatment in 1 rapid procedure by using 4 standard components: (1) targeted gold colloids; (2) liposomal drugs; (3) a laser pulse; and (4) radiation, all at safe doses. The therapeutic strength of quadrapeutics increases with cancer aggressiveness. In animal models of a primary and microscopic residual HNSCC, quadrapeutics increased the efficacy of standard chemoradiation therapy by more than 17‐fold by using only 3% to 6% of clinical doses of drug and radiation, did not cause side effects, and detected residual microtumors in vivo intraoperatively. Quadrapeutics can be applied to detect and eradicate HNSCC and similar microtumors in a safe and rapid theranostic procedure. © 2015 Wiley Periodicals, Inc. Head Neck 37: 1547–1555, 2015     

Left ventricular assist device support reverses altered cardiac expression and function of natriuretic peptides and receptors in end-stage heart failure

OBJECTIVE: Atrial (ANP) and B-type natriuretics peptides (BNP) via their guanylyl cyclase-A (GC-A) receptor not only regulate arterial blood pressure and volume but also exert local antihypertrophic, antifibrotic and lusitropic effects in the heart. To elucidate whether cardiac hypertrophy/insufficiency and reversal is associated with changes in the local responsiveness to NPs, we compared the mRNA expression of ANP, BNP and receptors and the responsiveness of GC-A to ANP in left ventricular tissue obtained from 10 patients with congestive heart failure (CHF) before and after hemodynamic unloading by left ventricular assist device (LVAD) support. METHODS AND RESULTS: Quantitative "real time" RT-PCR demonstrated that the mRNA expression levels of ANP, BNP and the NP-metabolizing NPR-C receptor were both markedly increased in human failing hearts. GC-A mRNA expression levels were not different from nonfailing hearts, but cGMP production by GC-A in response to ANP was nearly abolished. Reversal of cardiomyocyte hypertrophy during LVAD support was accompanied by normalization of ANP, BNP and NPR-C mRNA levels and a significant recovery of GC-A responsiveness to ANP. CONCLUSION: In CHF patients, increased local clearance by NPR-C receptors and diminished responsiveness of cardiac GC-A might impair the local antihypertrophic effects of natriuretic peptides and contribute to the progression of cardiac hypertrophy and insufficiency. Reverse remodeling during LVAD support reverses these changes and can thereby recuperate the local protective effects of ANP and BNP.     

Association of coronary atherosclerosis with insulin resistance in patients with impaired glucose tolerance

OBJECTIVES: The purpose of the study was to evaluate the role of insulin resistance (IR) in the development of coronary atherosclerosis in patients with impaired glucose tolerance. METHODS AND RESULTS: The study group consisted of 42 patients with impaired glucose tolerance. Based upon coronary angiography the patients were divided into group A--with prior myocardial infarction and critical coronary stenosis (n=20) and group B--without prior myocardial infarction and without critical coronary stenosis (n=22). In each patient glucose disposal rate (GDR) during metabolic clamp, insulinaemia in the fasting state and during the clamp, glycaemia during oral glucose tolerance test (OGTT), BMI and body mass composition were measured. The groups did not differ in age, BMI, percent fat content and distribution, and blood pressure. Fasting insulinaemia (56.7 microU/ml) was higher in group A than in group B (22.3 microU/ml). GDR in group A (2.96 mg/kg b.m./min) was lower than in group B (5.36 mg/kg b.m./min). There was a negative correlation between the number of critically narrowed coronary vessels and GDR in group A. GDR below 3.97 mg/kg b.m./min was found, based on regression analysis, to be a powerful risk factor for myocardial infarction. CONCLUSIONS: The relationship between IR and severity of coronary atherosclerosis implies its unfavourable role in the development of atherosclerosis. The present findings indicate a negative role of IR in the development of myocardial infarction and suggest that it is an independent risk factor, which identifies high-risk patients requiring treatment that would increase tissue insulin sensitivity.     

Proximal Esophageal Contractions in Laryngectomized Patients

After laryngectomy for treatment of laryngeal cancer, the distal esophageal contractions have low amplitude. Our hypothesis is that proximal esophageal contractions are also impaired. We studied the proximal esophageal contractions in 20 laryngectomized patients (16 men) with a mean age of 44.2 years, 12 rehabilitated patients with esophageal speech, and 12 controls (7 men, mean age of 46.5 years). We used the manometric method with continuous perfusion. All subjects were studied in the sitting position and performed five swallows of a 5-ml bolus of water alternated with five dry swallows. The contractions were measured 2 cm below the high-pressure zone of the pharyngoesophageal transition. The results showed that the amplitude and duration of contractions were different in laryngectomized patients compared with controls. The amplitude of contractions of patients (wet swallows: 37.3 ± 20.7 mmHg, mean ± SD) was lower than that of controls (81.1 ± 31.7 mmHg). The duration of contractions was also lower in laryngectomized patients (2.2 ± 0.7 s) than in controls (2.6 ± 0.6 s). We conclude that the proximal esophageal contraction amplitude and duration of laryngectomized patients are lower than controls, a fact suggesting that laryngectomy may affect the proximal esophageal contractions.