In Situ LSPR Sensing of Secreted Insulin in Organ-on-Chip.

Organ-on-a-chip (OOC) devices offer new approaches for metabolic disease modeling and drug discovery by providing biologically relevant models of tissues and organs in vitro with a high degree of control over experimental variables for high-content screening applications. Yet, to fully exploit the potential of these platforms, there is a need to interface them with integrated non-labeled sensing modules, capable of monitoring, in situ, their biochemical response to external stimuli, such as stress or drugs. In order to meet this need, we aim here to develop an integrated technology based on coupling a localized surface plasmon resonance (LSPR) sensing module to an OOC device to monitor the insulin in situ secretion in pancreatic islets, a key physiological event that is usually perturbed in metabolic diseases such as type 2 diabetes (T2D). As a proof of concept, we developed a biomimetic islet-on-a-chip (IOC) device composed of mouse pancreatic islets hosted in a cellulose-based scaffold as a novel approach. The IOC was interfaced with a state-of-the-art on-chip LSPR sensing platform to monitor the in situ insulin secretion. The developed platform offers a powerful tool to enable the in situ response study of microtissues to external stimuli for applications such as a drug-screening platform for human models, bypassing animal testing.

Unravelling the Role of Electric and Magnetic Dipoles in Biosensing with Si Nanoresonators.

High refractive index dielectric nanoresonators are attracting much attention due to their ability to control both electric and magnetic components of light. Due to the combination of confined modes with reduced absorption losses, they have recently been proposed as an alternative to nanoplasmonic biosensors. In this context, we study the use of semirandom silicon nanocylinder arrays, fabricated with simple and scalable colloidal lithography for the efficient and reliable detection of biomolecules in biological samples. Interestingly, electric and magnetic dipole resonances are associated with two different transduction mechanisms: extinction decrease and resonance red shift. By contrasting both observables, we identify clear advantages in tracking changes in the extinction magnitude. Our data demonstrate that, despite its simplicity, the proposed platform is able to detect prostate-specific antigen in human serum with limits of detection meeting clinical needs.

Self-Calibrating On-Chip Localized Surface Plasmon Resonance Sensing for Quantitative and Multiplexed Detection of Cancer Markers in Human Serum.

The need for point-of-care devices able to detect diseases early and monitor their status, out of a lab environment, has stimulated the development of compact biosensing configurations. Whereas localized surface plasmon resonance (LSPR) sensing integrated into a state-of-the-art microfluidic chip stands as a promising approach to meet this demand, its implementation into an operating sensing platform capable of quantitatively detecting a set of molecular biomarkers in an unknown biological sample is only in its infancy. Here, we present an on-chip LSPR sensor capable of performing automatic, quantitative, and multiplexed screening of biomarkers. We demonstrate its versatility by programming it to detect and quantify in human serum four relevant human serum protein markers associated with breast cancer.

On-a-chip Biosensing Based on All-Dielectric Nanoresonators.

Nanophotonics has become a key enabling technology in biomedicine with great promises in early diagnosis and less invasive therapies. In this context, the unique capability of plasmonic noble metal nanoparticles to concentrate light on the nanometer scale has widely contributed to biosensing and enhanced spectroscopy. Recently, high-refractive index dielectric nanostructures featuring low loss resonances have been proposed as a promising alternative to nanoplasmonics, potentially offering better sensing performances along with full compatibility with the microelectronics industry. In this letter we report the first demonstration of biosensing with silicon nanoresonators integrated in state-of-the-art microfluidics. Our lab-on-a-chip platform enables detecting Prostate Specific Antigen (PSA) cancer marker in human serum with a sensitivity that meets clinical needs. These performances are directly compared with its plasmonic counterpart based on gold nanorods. Our work opens new opportunities in the development of future point-of-care devices toward a more personalized healthcare.

Dosimetric comparison of 3-dimensional conformal and field-in-field radiotherapy techniques for the adjuvant treatment of early stage endometrial cancer.

BACKGROUND: The purpose of this study is to compare field-in-field radiotherapy (FIF) with conformal radiotherapy (CRT) in terms of dosimetric benefits for early stage endometrial cancer patients. MATERIALS AND METHODS: Ten consecutive early stage endometrial cancer patients who underwent adjuvant external beam radiotherapy were included in the study. For each patient, two different treatment plans were created. FIF and CRT plans were compared for doses in the planning target volume (PTV), the organ at risk (OAR) volumes including rectum, bladder, bowel, bilateral femurs and bone marrow, the dose homogeneity index, and the monitor unit counts required for the treatment. RESULTS: The FIF technique significantly reduced the maximum dose of the PTV, rectum, bladder, bowel, left femur, right femur and bone marrow (p values were: <0.001, 0.031, 0.003, <0.001, 0.001, 0.001 and <0.001 respectively). When the OAR volumes irradiated with >30 and >45 Gy were compared, the results were in favor of the FIF technique. The volumes of rectum, bladder, bowel, left femur, right femur and bone marrow receiving more than the prescription dose of 45 Gy were significantly reduced with FIF technique (p values were 0.016, 0.039, 0.01, 0.04, 0.037 and 0.01 respectively). The dose homogeneity index (DHI) was significantly improved with FIF technique (p < 0.001). CONCLUSIONS: FIF allowed more homogeneous dose distribution in the PTV and reduced the doses received by OAR. Considering the lower maximum doses in the OAR and PTV, FIF technique seems to be more advantageous than CRT during adjuvant radiotherapy for early stage endometrial cancer patients.

Plasmon interferometers for high-throughput sensing.

In this letter, we demonstrate a refractive index sensor based on a subwavelength plasmon interferometer. Illumination of an atilt subwavelength slit-grove pair on a metal surface with monochromatic light generates high-contrast interference fringes of the transmitted light. Detection of the refractive index of the dielectric medium on the metal surface is based on examining the relative position of the interference fringes. Integration of the plasmon interferometer with a microfluidic channel provides a sensitive, high-throughput sensor with small detection volume.

Chemotherapy-induced Hepatitis B virus reactivation in HbsAg positive cancer patients: a single center experience.

Hepatitis B reactivation due to chemotherapy is a cause of serious morbidity and mortality in some of the patients with cancer. In this study, we retrospectively assessed the prevalence of hepatitis B reactivation among the patients undergoing cytotoxic chemotherapy. We investigated efficacy of lamivudine prophylaxis against hepatitis B reactivation as well.

The acute effect of tropisetron on ECG parameters in cancer patients.

OBJECTIVES: The 5-hydroxytryptamine 3 receptor antagonists, including tropisetron, ondansetron, granisetron, and dolasetron are agents used effectively for supportive care. They are used for the prevention and treatment of chemotherapy and radiotherapy-induced emesis. Despite their overall excellent safety profile, some electrocardiographic changes related to heart rate and repolarization were reported. Ondansetron, granisetron, and dolasetron were studied on this manner. But to our knowledge, there is no information about the cardiac side effects of tropisetron. In this study, we aimed to determine the acute effects of tropisetron on ECG parameters related to repolarization, heart rate, and systemic blood pressure. MATERIALS AND METHODS: Fifty-five cancer patients who received tropisetron for the prevention of acute chemotherapy-induced nausea and vomiting were enrolled into this single center, prospective study. Standard 12-lead ECG recordings were performed at baseline and 30 min after tropisetron (5 mg given over 1 min IV bolus) administration. P wave durations and corrected QT intervals were measured; P wave dispersion and QTc dispersion were calculated. RESULTS: In comparison with baseline, mean heart rate significantly decreased 30 min after administration of tropisetron. Tropisetron did not result in a significant change in P wave duration, corrected QT interval, P dispersion, and QTc dispersion. CONCLUSION: In this study, tropisetron did not show any ventricular and atrial arrhythmogenic effect because of repolarization abnormalities. Only it may cause a slight decrease in heart rate.

The acute effect of trastuzumab infusion on ECG parameters in metastatic breast cancer patients.

OBJECTIVES: Although trastuzumab therapy is known to be associated with congestive heart failure, its arrhythmogenic potential has not been studied in detail. The purpose of this study was to determine the acute influence of trastuzumab infusion on electrocardiogram (ECG) parameters in patients with metastatic breast cancer. PATIENTS AND METHODS: Twenty patients with HER2 overexpressing metastatic breast cancer and normal cardiac function were enrolled in this single-centre prospective study. Standard 12-lead ECG recordings were performed at baseline and after trastuzumab infusion (2 mg/kg given over 30 min). P-wave durations, QT and RR intervals were measured and QT dispersion (QTd) and P-wave dispersion (Pd) were calculated. RESULTS: In comparison with baseline, no statistically significant change in any ECG parameters, including QT and RR intervals, P wave durations, Pd and QTd, was observed after infusion of trastuzumab. CONCLUSION: In this study, no abnormality of atrial and ventricular depolarisation and repolarisation, indicated by Pd and QTd, was detected after infusion of trastuzumab. As Pd and QTd are both known to be associated with increased risk of serious arrhythmias and sudden death, it would appear that trastuzumab has no acute arrhythmogenic potential related to cardiac depolarisation and repolarisation.

Factors affecting survival in breast cancer patients following bone metastasis.

AIMS AND BACKGROUND: The purpose of the study was to identify prognostic factors that affect survival following bone metastasis in breast cancer patients with first metastases in the skeletal system. METHODS AND STUDY DESIGN: We analyzed retrospectively the data of 248 metastatic breast cancer patients whose first distant metastasis was in the skeleton. RESULTS: The median age of the patients at diagnosis was 46 years (range, 23-76). Nearly half of the patients were premenopausal (52.4%). The median disease-free survival was 24 months. For most of the patients (221), bone was the sole first metastatic site, and the disease remained confined to the bone in 99 of them. The remaining patients (n = 27) had both bone and visceral metastasis at the time of first relapse. One hundred and fourteen of the patients (46%) had died by the time of analysis. With the median follow-up of 50.5 months from diagnosis, median survival after bone metastasis was 32 months. In univariate analyses, statistically significant predictors for survival after bone metastasis were axillary lymph node status, T stage of disease, hormone receptor status of the primary tumor, the presence of lymphovascular invasion, involvement of skin, the presence of additional nonosseous metastatic sites at the time of bone relapse, and disease-free interval. In multivariate analyses, the presence of additional non-osseous metastatic sites at the time of bone relapse, T stage of disease, hormone receptor status of the primary tumor, and the presence of lymphovascular invasion were found to be significant independent prognostic factors. CONCLUSIONS: In the result of study, for patients with breast cancer, survival following bone metastasis is affected by secondary prognostic factors such as disease-free interval and extent of metastasis besides primary prognostic factors related to the primary tumor.

Transit thrombus entrapped in patent foramen ovale resolved without clinical embolic events.

We describe a case of impending paradoxic embolism in a 35-year-old woman who had a diagnosis of metastatic breast carcinoma. The patient presented with acute pulmonary embolism and was treated with anticoagulation therapy without any sign of a clinical embolic event.

Synchronous presentation of nasopharyngeal and renal cell carcinomas.

We report a rare case of synchronous presentation of nasopharyngeal and renal cell carcinomas in a-50-year old male patient with long standing smoking history. The patient was initially presented with a diagnosis of nasopharyngeal carcinoma. During staging process, the abdominal computed tomography detected a right renal solid mass, 6.5 cm in diameter, originating from posterior portion of the right renal cortex. Right radical nephrectomy was performed and pathological examination revealed renal cell carcinoma. Smoking was thought to be a risk factor for both cancers. Systemic evaluation of kidney should not be discarded in patients diagnosed with nasopharyngeal carcinoma living in western countries with a smoking history.

Synchronous presentation of nasopharyngeal and renal cell carcinomas

We report a rare case of synchronous presentation of nasopharyngeal and renal cell carcinomas in a-50-year old male patient with long standing smoking history. The patient was initially presented with a diagnosis of nasopharyngeal carcinoma. During staging process, the abdominal computed tomography detected a right renal solid mass, 6.5 cm in diameter, originating from posterior portion of the right renal cortex. Right radical nephrectomy was performed and pathological examination revealed renal cell carcinoma. Smoking was thought to be a risk factor for both cancers. Systemic evaluation of kidney should not be discarded in patients diagnosed with nasopharyngeal carcinoma living in western countries with a smoking history.