Definitive local therapy to head and neck squamous cell carcinoma with distant metastasis.

Objectives: Data on the efficacy of including definitive local therapy to the primary site for head and neck squamous cell carcinoma (HNSCC) patients with synchronous distant metastasis are lacking. In multiple different solid tumor types, there has been benefit when using systemic therapy followed by local consolidative therapy (stereotactic ablative radiotherapy or surgery) directed at metastases. We proposed to retrospectively evaluate patients at our institution that received definitive treatment to the primary.

Proteomic profile of melanoma cell-derived small extracellular vesicles in patients' plasma: a potential correlate of melanoma progression.

Molecular profiling of small extracellular vesicles (sEV) isolated from plasma of cancer patients emerges as promising strategy for biomarkers discovery. We investigated the proteomic profiles of sEV immunoselected using anti-CSPG4 antibodies from 15 melanoma patients' plasma. The proteomes of sEV separated into melanoma cell-derived (MTEX) and non-malignant cell-derived (NMTEX) were compared using high-resolution mass spectrometry.

Extracellular HMGB-1 activates inflammatory signaling in tendon cells and tissues.

Background: Increasing evidence indicates that secretion of high mobility group box 1 protein (HMGB-1) is functionally associated with tendinopathy development. However, the underlying effect and mechanism of extracellular HMGB-1 on tendon cells are unclear.

Methods: We tested the effect of exogenous HMGB-1 on cell growth, migration, and inflammatory signaling responses with isolated rat Achilles tendon cells.

Pulse Pressure and the Risk of End-Stage Renal Disease Among Chinese Adults in Singapore: The Singapore Chinese Health Study.

Background Although hypertension is an established risk factor for chronic kidney disease, less is known about the relationship of pulse pressure (PP), a measure of arterial stiffness, with chronic kidney disease. We investigated the association of systolic blood pressure (BP), diastolic BP, PP, and mean arterial pressure with the risk of end-stage renal disease (ESRD) in the prospective population-based Singapore Chinese Health Study. Methods and Results We used data from 30 636 participants who had BP measured at ages 46 to 85 years during follow-up I interviews between 1999 and 2004.

DASH Dietary Pattern, Mediation by Mineral Intakes, and the Risk of Coronary Artery Disease and Stroke Mortality.

Background The association of the Dietary Approaches to Stop Hypertension ( DASH ) dietary pattern with stroke and coronary artery disease ( CAD ) mortality has not been evaluated in Asian populations, and the role of mineral intakes as potential mediators is not clear. Methods and Results We used data from 57 078 participants of the Singapore Chinese Health Study aged 45 to 74 years at baseline (1993-1998). Information on usual diet was collected by a validated 165-item food frequency questionnaire at recruitment, and mortality information was obtained via registry linkage up to December 31, 2014.

PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS.

Background: The rarity of mutations in PALB2, CHEK2 and ATM make it difficult to estimate precisely associated cancer risks. Population-based family studies have provided evidence that at least some of these mutations are associated with breast cancer risk as high as those associated with rare BRCA2 mutations. We aimed to estimate the relative risks associated with specific rare variants in PALB2, CHEK2 and ATM via a multicentre case-control study.

In vivo inflammation imaging using a CB2R-targeted near infrared fluorescent probe.

Chronic inflammation is considered as a critical cause of a host of disorders, such as cancer, rheumatoid arthritis, atherosclerosis, and neurodegenerative diseases, although the exact mechanism is yet to be explored. Imaging tools that can specifically target inflammation are therefore important to help reveal the role of inflammation in disease progression, and allows for developing new therapeutic strategies to ultimately improve patient care. The purpose of this study was to develop a new in vivo inflammation imaging approach by targeting the cannabinoid receptor type 2 (CB2R), an emerging inflammation biomarker, using a unique near infrared (NIR) fluorescent probe.

Intestinal stem cell injury and protection during cancer therapy.

Radiation and chemotherapy remain the most effective and widely used cancer treatments. These treatments cause DNA damage and selectively target rapidly proliferating cells such as cancer cells, as well as inevitably cause damage to normal tissues, particularly those undergoing rapid self renewal. The side effects associated with radiation and chemotherapy are most pronounced in the hematopoietic (HP) system and gastrointestinal (GI) tract.

Ionizing irradiation induces acute haematopoietic syndrome and gastrointestinal syndrome independently in mice.

The role of bone marrow (BM) and BM-derived cells in radiation-induced acute gastrointestinal (GI) syndrome is controversial. Here we use bone marrow transplantation (BMT), total body irradiation (TBI) and abdominal irradiation (ABI) models to demonstrate a very limited, if any, role of BM-derived cells in acute GI injury and recovery. Compared with WT BM recipients, mice receiving BM from radiation-resistant PUMA KO mice show no protection from crypt and villus injury or recovery after 15 or 12 Gy TBI, but have a significant survival benefit at 12 Gy TBI.

Role of apoptosis in colon cancer biology, therapy, and prevention.

Deregulation of apoptosis is a hallmark of human cancer and contributes to therapeutic resistance. Recent advances in cancer genomics reveal a myriad of alterations in key pathways that directly or indirectly increase tumor cell survival. This review will outline the pathways of apoptosis in mammalian cells, and highlight the common alterations of apoptosis regulators found in colon cancer, the role of apoptosis and underlying mechanisms in colon cancer treatment and prevention, including recent advances on investigational agents, such as kinase inhibitors, proteasome inhibitors, HSP90 inhibitors, BH3 mimetics, TRAIL, and IAP antagonists.

New therapeutic strategies in the second line setting of advanced or metastatic pancreatic adenocarcinoma.

Pancreatic cancer is a lethal disease and its prognosis remains dismal. The modest results of existing available treatments in the second line setting reveal the need of new therapeutic strategies. In this year's American Society of Clinical Oncology (ASCO) Annual Meeting two remarkable trials and one retrospective analysis were presented regarding this vulnerable group of patients.

Immune responses to cancer: are they potential biomarkers of prognosis?

Recent technical improvements in evaluations of immune cells in situ and immune monitoring of patients with cancer have provided a wealth of new data confirming that immune cells play a key role in human cancer progression. This, in turn, has revived the expectation that immune endpoints might serve as reliable biomarkers of outcome or response to therapy in cancer. The recent successes in linking the T-cell signature in human colorectal carcinoma (CRC) with prognosis have provided a strong motive for searching for additional immune biomarkers that could serve as intermediate endpoints of response to therapy and outcome in human cancers.

Utility of 3'-[(18)F]fluoro-3'-deoxythymidine as a PET tracer to monitor response to gene therapy in a xenograft model of head and neck carcinoma.

Noninvasive imaging methodologies are needed to assess treatment responses to novel molecular targeting approaches for the treatment of squamous cell carcinoma of the head and neck (SCCHN). Computer tomography and magnetic resonance imaging do not effectively distinguish tumors from fibrotic tissue commonly associated with SCCHN tumors. Positron emission tomography (PET) offers functional non-invasive imaging of tumors.

Influence of CD8+ T regulatory cells on intraocular tumor development.

The interior of the eye, or uvea, is a site of immune privilege where certain immune responses are attenuated or completely excluded to protect non-regenerating tissues essential for vision. One consequence of this immunoregulation is compromised immune mediated elimination of intraocular tumors. For example, certain murine tumor cell lines which are rejected by host immune responses when transplanted in the skin grow progressively when placed in the anterior chamber (a.

Behavioral patterns associated with chemotherapy-induced emesis: a potential signature for nausea in musk shrews.

Nausea and vomiting are common symptoms in patients with many diseases, including cancer and its treatments. Although the neurological basis of vomiting is reasonably well known, an understanding of the physiology of nausea is lacking. The primary barrier to mechanistic research on the nausea system is the lack of an animal model.

Strategies for discovery of small molecule radiation protectors and radiation mitigators.

Mitochondrial targeted radiation damage protectors (delivered prior to irradiation) and mitigators (delivered after irradiation, but before the appearance of symptoms associated with radiation syndrome) have been a recent focus in drug discovery for (1) normal tissue radiation protection during fractionated radiotherapy, and (2) radiation terrorism counter measures. Several categories of such molecules have been discovered: nitroxide-linked hybrid molecules, including GS-nitroxide, GS-nitric oxide synthase inhibitors, p53/mdm2/mdm4 inhibitors, and pharmaceutical agents including inhibitors of the phosphoinositide-3-kinase pathway and the anti-seizure medicine, carbamazepine. Evaluation of potential new radiation dose modifying molecules to protect normal tissue includes: clonogenic radiation survival curves, assays for apoptosis and DNA repair, and irradiation-induced depletion of antioxidant stores.

Modulation of signal transducers and activators of transcription 1 and 3 signaling in melanoma by high-dose IFNalpha2b.

Purpose: The Janus-activated kinase/signal transducers and activators of transcription (STAT) pathway of IFN signaling is important to immunoregulation and tumor progression. STAT1 plays a prominent role in the effector immune response, whereas STAT3 is implicated in tumor progression and down-regulation of the response to type I IFNs. The goal of this study was to understand the effects of high-dose IFNalpha2b (HDI) in relation to the balance of pSTAT1 and pSTAT3.