Src-type tyrosine kinase p56lck is critical for thymic stromal lymphopoietin-induced allergic rhinitis.

BACKGROUND: Thymic stromal lymphopoietin (TSLP) is a regulator of mast cell-mediated allergic inflammatory reactions, but the manner in which TSLP contributes to allergic rhinitis (AR) remains unclear. OBJECTIVE: Here, we sought to determine that TSLP plays a crucial role in AR by interacting with Src-type tyrosine kinase p56lck and STAT6 and promoting mast cells degranulation. METHODS: The effects of TSLP on mast cell degranulation and AR were analysed in human mast cell line (HMC-1 cells), ovalbumin (OVA)-induced AR animal model, and human subjects. Small interfering RNA experiments were performed in HMC-1 cells and OVA-induced AR model. Immune responses were analysed by enzyme-linked immunosorbent assay, Western blotting, immunoprecipitation, and histological studies. RESULTS: Thymic stromal lymphopoietin levels and mast cell-derived p56lck activation were elevated in human subjects with AR, and in AR mice, exogenous TSLP accelerated TH2-allergic inflammatory reactions by up-regulating p56lck and STAT6. On the other hand, depletion of TSLP, p56lck, and STAT6 ameliorated clinical symptoms in AR mice. The selective inhibitor of p56lck, damnacanthal, inhibits AR reactions. CONCLUSION: Collectively, these observations suggest a role for TSLP/p56lck/STAT6 in AR and offer insight into potential therapeutic strategies.

Nodal factors predictive of recurrence and survival in patients with oral cavity squamous cell carcinoma.

OBJECTIVES: Lymph node (LN) metastasis of oral cavity squamous cell carcinoma (OSCC) is associated with survival outcomes. However, the relationship between different metastatic nodal factors and treatment outcomes requires further elucidation. This study examined nodal factors predictive of recurrence and survival in patients with OSCC. METHODS: This prospective observational study included 157 patients with OSCC who underwent surgery between 2010 and 2015. Clinicopathological and follow-up information were recorded. Univariate and multivariate Cox proportional hazard models were performed to identify factors associated with recurrence-free survival, disease-specific survival and overall survival. RESULTS: Sixty-five of 157 patients (41.4%) had neck metastasis. During a median follow-up of 46 months, any recurrences and all deaths occurred in 43 (27.4%) and 43 (27.4%) of cases, respectively. All nodal factors (LN classification, size, number and ratio) and extra-nodal extension were significantly associated with all survival outcomes (P < .001). Multivariate analyses indicated that a tumour size >2 cm and LN ratio were independently associated with all survival (P < .05). Patients with LN ratio >0.05 had sixfold higher recurrence and mortality rates than other patients (P < .001). CONCLUSION: Lymph node ratio is an independent and predictive determinant of post-treatment recurrence and survival.

Postdiagnostic use of ß-blockers and other antihypertensive drugs and the risk of recurrence and mortality in head and neck cancer patients: an observational study of 10,414 person-years of follow-up.

INTRODUCTION: Growing evidence indicates that norepinephrine promotes cancer growth and metastasis whereas ß-blockers decrease these risks. This study aimed to examine the clinical impact of ß-blockers and other hypertensive drugs on disease recurrence and survival in patients with head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: This study analyzed a cohort of 1274 consecutive patients who received definitive treatments for previously untreated HNSCC at our tertiary referral center between January 2001 and December 2012. Antihypertensive use was considered positive if patients were on medication from HNSCC diagnosis to at least 1 year after treatment initiation. Cox proportional hazard models were utilized to determine associations between antihypertensive drugs and recurrence, survival, and second primary cancer (SPC) occurrence. RESULTS: Hypertension itself was not a significant variable of recurrence and survival and no antihypertensive drug use affected SPC occurrence (all P > 0.1). After controlling for clinical factors, calcium-channel blocker use remained an independent variable for index cancer recurrence, and ß-blocker use was significantly associated with poor cancer-specific mortality, competing mortality, and all-cause mortality (all P < 0.05). ß-blocker use significantly affected competing and all-cause mortalities in normotensive patients, and calcium-channel blocker use affected index cancer recurrence in normotensive patients (all P < 0.05). CONCLUSIONS: Our data show that ß-blocker use is associated with decreased survival and calcium-channel blockers is associated with increased cancer recurrence in patients of HNSCC.

Ectopic pregnancy occurring in the remnant tube of a previous adnexectomy: a case report.

Ectopic pregnancy occurring in the same region is a comparatively rare disease, but sometimes it is very serious to patients if it is delayed. The authors present a case of spontaneous ectopic pregnancy occurring in the ipsilateral salpingectomy stump of a previous adnexectomy that was successfully removed via laparoscopic surgery without complication. This case may support the idea of intrauterine transmigration of a fertilized egg as an etiology of spontaneous ectopic pregnancy. Thus, the potential for ectopic pregnancy in the tubal remnant in cases of previous salpingectomy or adnexectomy needs to be carefully considered.

Capsaicin attenuates spermatogenic cell death induced by scrotal hyperthermia through its antioxidative and anti-apoptotic activities.

This study was performed to examine whether capsaicin, the main pungent ingredient of red peppers, exerts protective effects against testicular injuries induced by transient scrotal hyperthermia. Capsaicin (0.33 mg kg-1 ) was administered subcutaneously to mice one hour before heat stress (HS) in a 43°C water bath for 20 min. After 7 days, mice exposed to HS showed low testicular weight, severe vacuolisation of seminiferous tubules followed by loss of spermatogenic cells, and appearance of multinucleated giant cells and remarkable TUNEL-positive apoptotic cells, as well as weak immunoreactivity of phospholipid hydroperoxide glutathione peroxidase (PHGPx) in spermatogenic cells. Levels of lipid peroxidation and heat shock 70-kDa protein 1 (Hsp72) and BCL2-associated X protein (Bax) mRNA were greatly increased, but PHGPx, manganese superoxide dismutase (MnSOD), and B-cell lymphoma-extra large (Bcl-xL) mRNAs were significantly diminished in the testes by HS. However, capsaicin pre-treatment significantly suppressed the spermatogenic cell death, oxidative stress (levels of MDA, PHGPx immunoreactivity, and Hsp72, PHGPx, and MnSOD mRNA) and apoptosis (levels of TUNEL-positive cells, and Bcl-xL and Bax mRNA) in testes by HS. These suggest that capsaicin has a protective effect against spermatogenic cell death induced by scrotal hyperthermia through its antioxidative and anti-apoptotic activities.

Incidence and risk factors of late recurrence in patients with salivary gland cancer.

OBJECTIVES: Recurrence in the late post-treatment period is relatively common in salivary gland cancer (SGC), but risk factors and survival associated with late recurrence have been rarely studied. We investigated the incidence and risk factors of SGC recurrence >5 years after treatment and associated survival. DESIGN: A retrospective cohort study. SETTING: University hospital. PARTICIPANTS: A total of 240 patients with previously untreated SGC who underwent definitive treatment. MAIN OUTCOME MEASURES: Late recurrence was defined as recurrence at a time point >5 years after treatment. Univariate and multivariable analyses were used to identify the association of clinicopathologic factors with recurrence-free survival (RFS), cancer-specific survival (CSS) and late recurrence. RESULTS: Of the 240 patients, 124 (51.7%) patients developed recurrence during a median follow-up of 160.0 months (range 121.5-282.2 months). Sixteen (6.7%) patients developed late recurrence; the median time to late recurrence was 92.5 months (range 60.2-138.3 months) after treatment. Multivariable analysis showed that primary site, histologic grade and N classification were independent variables of both RFS and CSS (P < 0.05 each). Extraparenchymal extension was also an independent variable of CSS (P = 0.022). In addition, a non-parotid tumour location was a significant factor for late recurrence in multivariable analysis (P = 0.017). The median overall survival after the development of late recurrence was 79.7 months (range 0.2-163.4 months), significantly longer than that after early recurrence (19.7 months) (P = 0.043). CONCLUSION: Late recurrence occurs in some SGC patients. Long-term close surveillance may be required for patients with non-parotid SGC.

Skeletonization algorithm-based blood vessel quantification using in vivo 3D photoacoustic imaging.

Blood vessels are the only system to provide nutrients and oxygen to every part of the body. Many diseases can have significant effects on blood vessel formation, so that the vascular network can be a cue to assess malicious tumor and ischemic tissues. Various imaging techniques can visualize blood vessel structure, but their applications are often constrained by either expensive costs, contrast agents, ionizing radiations, or a combination of the above. Photoacoustic imaging combines the high-contrast and spectroscopic-based specificity of optical imaging with the high spatial resolution of ultrasound imaging, and image contrast depends on optical absorption. This enables the detection of light absorbing chromophores such as hemoglobin with a greater penetration depth compared to purely optical techniques. We present here a skeletonization algorithm for vessel architectural analysis using non-invasive photoacoustic 3D images acquired without the administration of any exogenous contrast agents. 3D photoacoustic images were acquired on rats (n = 4) in two different time points: before and after a burn surgery. A skeletonization technique based on the application of a vesselness filter and medial axis extraction is proposed to extract the vessel structure from the image data and six vascular parameters (number of vascular trees (NT), vascular density (VD), number of branches (NB), 2D distance metric (DM), inflection count metric (ICM), and sum of angles metric (SOAM)) were calculated from the skeleton. The parameters were compared (1) in locations with and without the burn wound on the same day and (2) in the same anatomic location before (control) and after the burn surgery. Four out of the six descriptors were statistically different (VD, NB, DM, ICM, p < 0.05) when comparing two anatomic locations on the same day and when considering the same anatomic location at two separate times (i.e. before and after burn surgery). The study demonstrates an approach to obtain quantitative characterization of the vascular network from 3D photoacoustic images without any exogenous contrast agent which can assess microenvironmental changes related to disease progression.

Ethanol and/or radiofrequency ablation to treat venolymphatic malformations that manifest as a bulging mass in the head and neck.

AIM: To evaluate the efficacy of ultrasound (US)-guided ethanol ablation (EA) and radiofrequency ablation (RFA) for treating venolymphatic malformations (VLM) of the head and neck. MATERIALS AND METHODS: US-guided EA and/or RFA were performed on 17 patients with VLM of the head and neck. Computed tomography (CT) or magnetic resonance imaging (MRI) was used to locate the cranial nerves and salivary gland ducts that were close to targets, and these were avoided during the procedures. Treatment response was assessed using volume reduction and cosmetic grading scoring. RESULTS: Nine VLMs were located close to the functional structures: Stensen's duct (n=3), cranial nerve branch (n=3), or both (n=3). All patients demonstrated >50% volume reduction, except one patient with a microcystic lymphatic malformation that was abutting the facial nerve. Median cosmetic grading scores improved from 4 to 1 (p<0.001). CONCLUSION: US-guided EA and/or RFA are effective and safe treatment methods in patients with VLMs of the head and neck. Treatment selection of EA and/or RFA could be performed based on the composition of VLMs as assessed at CT and MRI.

Routine endoscopic screening for synchronous esophageal neoplasm in patients with head and neck squamous cell carcinoma: a prospective study.

Early detection of synchronous esophageal squamous cell neoplasm (ESCN) in head and neck squamous cell carcinoma (HNSCC) patients can significantly affect their prognosis. We investigated the prevalence of synchronous ESCN and the risk factors for developing ESCN in patients with HNSCC, and evaluated the effect of routine endoscopic screening in these patients. Subjects who were diagnosed as HNSCC from May 2010 to January 2014 were eligible. All patients underwent conventional white light endoscopic examinations with narrow band imaging and Lugol chromoendoscopy. Among 458 subjects screened, 28 synchronous ESCN were detected in 24 patients (5.2%). The prevalence of ESCN was greatest in patients with hypopharyngeal cancer (20.9%). In multivariate analysis, pyriform sinus involvement was independent risk factor for developing synchronous ESCN (odds ratio 171.2, P < 0.001). During the follow-up period (median, 24 months), the 3-year overall survival rates was significantly lower in patients with ESCN than in patients without ESCN (54.2% vs. 78.3%, P = 0.0013). Routine endoscopic screening for detecting synchronous ESCN should be recommended for patients with HNSCC, especially those with pyriform sinus involvement.

Growth retardation at early life and metabolic adaptation among North Korean children.

The high prevalence of obesity is a major public health issue and contributes to the 'double burden' of disease in developing countries. Early exposure to poor nutrition may cause metabolic adaptations that, when accompanied by exposure to 'affluent' nutrition, may increase the risk for obesity and other metabolic disorders. The aim of this study was to determine differences in energy metabolism and nutritional status between normal-height and growth-retarded North Korean children living in South Korea. A total of 29 children were recruited and underwent measurements of resting energy expenditure (REE), respiratory quotient (RQ), anthropometrics and dietary intake. There was no difference in REE or any assessment of obesity between the growth-retarded and normal-height children. Children who were classified as growth retarded (HAZ<-1.0) or stunted (HAZ<-2.0) had a significantly higher RQ (ß=0.036 or 0.060, respectively, P=0.018 or 0.016), independent of sex, age, fat-free mass, fat mass and food quotient, compared with children with normal height. The results from this study, the first from an Asian population, add to the growing body of literature suggesting that undernutrition early in life results in adaptations in energy metabolism that favor fat deposition, increasing the risk of stunted children becoming overweight or obese later in life. Continued research on this topic is warranted, given the continued rise in the prevalence of the double burden in transitional countries.

PPARγ induces growth inhibition and apoptosis through upregulation of insulin-like growth factor-binding protein-3 in gastric cancer cells

Peroxisome proliferator activator receptor-gamma (PPARγ) is a ligand-activated transcriptional factor involved in the carcinogenesis of various cancers. Insulin-like growth factor-binding protein-3 (IGFBP-3) is a tumor suppressor gene that has anti-apoptotic activity. The purpose of this study was to investigate the anticancer mechanism of PPARγ with respect to IGFBP-3. PPARγ was overexpressed in SNU-668 gastric cancer cells using an adenovirus gene transfer system. The cells in which PPARγ was overexpressed exhibited growth inhibition, induction of apoptosis, and a significant increase in IGFBP-3 expression. We investigated the underlying molecular mechanisms of PPARγ in SNU-668 cells using an IGFBP-3 promoter/luciferase reporter system. Luciferase activity was increased up to 15-fold in PPARγ transfected cells, suggesting that PPARγ may directly interact with IGFBP-3 promoter to induce its expression. Deletion analysis of the IGFBP-3 promoter showed that luciferase activity was markedly reduced in cells without putative p53-binding sites (-Δ1755, -Δ1795). This suggests that the critical PPARγ-response region is located within the p53-binding region of the IGFBP-3 promoter. We further demonstrated an increase in PPARγ-induced luciferase activity even in cells treated with siRNA to silence p53 expression. Taken together, these data suggest that PPARγ exhibits its anticancer effect by increasing IGFBP-3 expression, and that IGFBP-3 is a significant tumor suppressor.

Radiation promotes invasiveness of non-small-cell lung cancer cells through granulocyte-colony-stimulating factor.

Despite ionizing radiation (IR) is being widely used as a standard treatment for lung cancer, many evidences suggest that IR paradoxically promotes cancer malignancy. However, its molecular mechanisms underlying radiation-induced cancer progression remain obscure. Here, we report that exposure to fractionated radiation (2 Gy per day for 3 days) induces the secretion of granulocyte-colony-stimulating factor (G-CSF) that has been commonly used in cancer therapies to ameliorate neutropenia. Intriguingly, radiation-induced G-CSF promoted the migratory and invasive properties by triggering the epithelial-mesenchymal cell transition (EMT) in non-small-cell lung cancer cells (NSCLCs). By irradiation, G-CSF was upregulated transcriptionally by ß-catenin/TCF4 complex that binds to the promoter region of G-CSF as a transcription factor. Importantly, irradiation increased the stability of ß-catenin through the activation of PI3K/AKT (phosphatidylinositol 3-kinase/AKT), thereby upregulating the expression of G-CSF. Radiation-induced G-CSF is recognized by G-CSFR and transduced its intracellular signaling JAK/STAT3 (Janus kinase/signal transducers and activators of transcription), thereby triggering EMT program in NSCLCs. Taken together, our findings suggest that the application of G-CSF in cancer therapies to ameliorate neutropenia should be reconsidered owing to its effect on cancer progression, and G-CSF could be a novel therapeutic target to mitigate the harmful effect of radiotherapy for the treatment of NSCLC.

Comparison of fine-needle aspiration and core needle biopsy under ultrasonographic guidance for detecting malignancy and for the tissue-specific diagnosis of salivary gland tumors.

BACKGROUND AND PURPOSE: Diagnostic test accuracy studies for ultrasonography-guided fine-needle aspiration and ultrasonography-guided core needle biopsy have shown inconclusive results due to their heterogenous study designs. Our aim was to compare the diagnostic accuracy of ultrasonography-guided fine-needle aspiration versus ultrasonography-guided core needle biopsy for detecting malignant tumors of the salivary gland and for the tissue-specific diagnosis of salivary gland tumors in a single tertiary hospital. MATERIALS AND METHODS: This retrospective study was approved by our institutional review board and informed consent was waived. Four hundred twelve patients who underwent ultrasonography-guided fine-needle aspiration (n = 155) or ultrasonography-guided core needle biopsy (n = 257) with subsequent surgical confirmation or clinical follow-up were enrolled. We compared the diagnostic accuracy of ultrasonography-guided fine-needle aspiration and ultrasonography-guided core needle biopsy regarding malignant salivary gland tumors and the correct tissue-specific diagnosis of benign and malignant tumors. We also tested the difference between these procedures according to the operator's experience and lesion characteristics. RESULTS: The inconclusive rates of ultrasonography-guided fine-needle aspiration and ultrasonography-guided core needle biopsy were 19% and 4%, respectively (P < .001). The overall accuracy of ultrasonography-guided core needle biopsy for diagnosing malignant tumors was significantly higher than that of ultrasonography-guided fine-needle aspiration (P = .024). The correct tissue-specific diagnosis rates of ultrasonography-guided fine-needle aspiration and ultrasonography-guided core needle biopsy were 95% versus 97% for benign tumors (P = .648) and 67% versus 80% for malignant tumors (P = .310). Trainees showed significantly lower accuracy with ultrasonography-guided fine-needle aspiration than with ultrasonography-guided core needle biopsy for diagnosing malignant tumors (P = .021). There was no difference between the diagnostic accuracy of ultrasonography-guided fine-needle aspiration and ultrasonography-guided core needle biopsy according to the internal composition of the lesions. There were no complications requiring intervention or hospitalization in our patients. CONCLUSIONS: Ultrasonography-guided core needle biopsy is superior to ultrasonography-guided fine-needle aspiration in detecting and characterizing malignant tumors of the salivary gland and could emerge as the diagnostic method of choice for patients presenting with a salivary gland mass.

PPARγ induces growth inhibition and apoptosis through upregulation of insulin-like growth factor-binding protein-3 in gastric cancer cells.

Peroxisome proliferator activator receptor-gamma (PPARγ) is a ligand-activated transcriptional factor involved in the carcinogenesis of various cancers. Insulin-like growth factor-binding protein-3 (IGFBP-3) is a tumor suppressor gene that has anti-apoptotic activity. The purpose of this study was to investigate the anticancer mechanism of PPARγ with respect to IGFBP-3. PPARγ was overexpressed in SNU-668 gastric cancer cells using an adenovirus gene transfer system. The cells in which PPARγ was overexpressed exhibited growth inhibition, induction of apoptosis, and a significant increase in IGFBP-3 expression. We investigated the underlying molecular mechanisms of PPARγ in SNU-668 cells using an IGFBP-3 promoter/luciferase reporter system. Luciferase activity was increased up to 15-fold in PPARγ transfected cells, suggesting that PPARγ may directly interact with IGFBP-3 promoter to induce its expression. Deletion analysis of the IGFBP-3 promoter showed that luciferase activity was markedly reduced in cells without putative p53-binding sites (-Δ1755, -Δ1795). This suggests that the critical PPARγ-response region is located within the p53-binding region of the IGFBP-3 promoter. We further demonstrated an increase in PPARγ-induced luciferase activity even in cells treated with siRNA to silence p53 expression. Taken together, these data suggest that PPARγ exhibits its anticancer effect by increasing IGFBP-3 expression, and that IGFBP-3 is a significant tumor suppressor.

Postoperative hypoalbuminemia as a risk factor for surgical site infection after oral cancer surgery.

OBJECTIVES: Postoperative surgical site infection (SSI) is a frequent postoperative complication in patients with oral cancer and significantly affects patient recovery and medical expenses. The aim of this study was to examine the predictors of SSI in patients undergoing major surgery for oral or oropharyngeal squamous cell carcinoma (OSCC) and to determine the relationship between perioperative albumin and the development of SSI. SUBJECTS AND METHODS: In 337 consecutive patients who underwent clean-contaminated surgery for OSCC, serum albumin, glucose, and hemoglobin levels were perioperatively measured. Differences between the groups were examined using Fisher's exact test, Mann-Whitney U-test, and multiple logistic regression analysis. RESULTS: Surgical site infection was detected in 88 (26.1%) patients with median time to development of 10 (2-25) days. Multiple logistic regression analysis showed that only postoperative serum albumin < 2.5 g dl(-1) was an independent variable predictive of SSI (P = 0.003). The duration of hospital stay was negatively correlated with postoperative albumin (R(2) = -0.302, P < 0.001). CONCLUSION: Early postoperative hypoalbuminemia <2.5 g dl(-1) is an independent risk factor for the development of SSI in patients undergoing oral cancer surgery. Clinicians should be aware of the implications of postoperative hypoalbuminemia and consider more intensive postoperative care in these patients.

Prognostic value of metastatic nodal volume and lymph node ratio in patients with cervical lymph node metastases from an unknown primary tumor.

OBJECTIVE: The presence of metastatic cervical lymph nodes (MCNs) is an unfavorable prognostic factor in head and neck cancer. The total volume of MCNs (MNV) and the lymph node ratio (LNR) may be superior to conventional nodal staging in cervical metastasis from an unknown primary tumor (CUP). We evaluated the prognostic value of MNV and LNR in CUP patients. METHODS: Thirty-nine patients with CUP who underwent surgery plus postoperative radiotherapy were reviewed. MNV was measured by preoperative computed tomography and LNR was determined using neck dissection samples. The association of clinicopathologic factors, MNV, and LNR with disease-free survival (DFS) and overall survival (OS) was analyzed. RESULTS: Five-year DFS and OS were 68.4 and 70.8%, respectively, for a median follow-up of 49 months. In multivariate analysis, MNV (>30 ml) was an independent prognostic factor for both DFS and OS (p = 0.004 and p < 0.001, respectively). LNR (>0.14) was identified as an independent predictive factor for DFS (p = 0.041). CONCLUSION: MNV and LNR are independent prognostic factors in patients with CUP and could facilitate the identification of high-risk patients requiring intensive treatment and surveillance.

Noncancer health events as a leading cause of competing mortality in advanced head and neck cancer.

BACKGROUND: The survival of patients with head and neck squamous cell carcinoma (HNSCC) can be affected by noncancer health events (NCHE) as well as by index cancer progression and second primary cancer (SPC). This study aimed to investigate the risk factors for NCHE and noncancer mortality (NCM) in patients with advanced-stage HNSCC. PATIENTS AND METHODS: This cohort study involved 600 consecutive patients with overall stage III to IV HNSCC who were treated between 2001 and 2010 at our tertiary referral hospital. NCHE was defined as re-admission (i.e. after the primary treatments for the index tumors) due to noncancer-related causes. The incidences of NCHE and NCM and their risk factors were analyzed by using cumulative incidence and cause-specific hazard functions. RESULTS: During a median follow-up period of 54 months, 224 (37.3%) and 55 (9.2%) of the 600 patients had NCHE and NCM, respectively. The 5-year index cancer mortality, SPC mortality, and NCM rates were 23.8%, 4.2%, and 8.9%, respectively. Multivariate analyses revealed that body mass index <20 kg/m(2) (P = 0.018), Charlson comorbidity index (CCI) ≥1 (P < 0.001), tumor recurrence (P < 0.001), SPC occurrence (P < 0.001), and initial chemotherapy (P = 0.049) were independent NCHE predictors. Older age (P < 0.001), CCI ≥1 (P = 0.008), tumor recurrence (P < 0.001), and SPC occurrence (P = 0.047) were independent NCM predictors. Patients with respiratory NCHE were at a higher risk of NCM than patients with other NCHE types (P < 0.001). CONCLUSIONS: One or more comorbidities, tumor recurrence, and SPC occurrence were independent predictors of both NCHE and NCM. Patients with respiratory NCHE had a particularly high risk of NCM.

A Dual Gold Nanoparticle System for Mesenchymal Stem Cell Tracking.

Stem cell-based therapies have demonstrated improved outcomes in preclinical and clinical trials for treating cardiovascular ischemic diseases. However, the contribution of stem cells to vascular repair is poorly understood. To elucidate these mechanisms, many have attempted to monitor stem cells following their delivery in vivo, but these studies have been limited by the fact that many contrast agents, including nanoparticles, are commonly passed on to non-stem cells in vivo. Specifically, cells of the reticuloendothelial system, such as macrophages, frequently endocytose free contrast agents, resulting in the monitoring of macrophages instead of the stem cell therapy. Here we demonstrate a dual gold nanoparticle system which is capable of monitoring both delivered stem cells and infiltrating macrophages using photoacoustic imaging. In vitro analysis confirmed preferential labeling of the two cell types with their respective nanoparticles and the maintenance of cell function following nanoparticle labeling. In addition, delivery of the system within a rat hind limb ischemia model demonstrated the ability to monitor stem cells and distinguish and quantify macrophage infiltration. These findings were confirmed by histology and mass spectrometry analysis. This work has important implications for cell tracking and monitoring cell-based therapies.

(18)F-FDG PET/CT surveillance at 3-6 and 12 months for detection of recurrence and second primary cancer in patients with head and neck squamous cell carcinoma.

BACKGROUND: Early detection of recurrence of head and neck squamous cell carcinoma (HNSCC), which is often obscured by surgical or radiotherapy-induced tissue distortion, is essential for proper patient management. METHODS: A total of 143 consecutive patients with previously untreated HNSCC were evaluated by whole-body fluorine 18-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) and regular clinical follow-up after curative treatment. The (18)F-FDG PET/CT was performed ∼3-6 and 12 months after treatment and findings suspicious for recurrence or SPC were confirmed using histopathology. RESULTS: The sensitivities of 3-6- and 12-month PET/CT scans at patient level were 96% and 93%, respectively, and those of regular clinical follow-up were 11% and 19%, respectively (McNemar test, P<0.001). In patients with no clinical suspicion, PET/CT detected 95% and 91% of recurrent patients at 3-6 and 12 months, respectively. The sensitivity of PET/CT for the identification of SPC was 29% and 80% at 3-6 and 12 months, respectively. A positive interpretation of PET/CT was significantly associated with poor overall survival (log-rank test, P<0.001). CONCLUSION: The (18)F-FDG PET/CT surveillance is beneficial for the detection of recurrence that may be missed by regular follow-up physical and endoscopic examinations of the head and neck area after curative treatment for HNSCC.

Phospho-Rb (Ser780) as a biomarker in patients with cervical lymph node metastases from an unknown primary tumour: a retrospective cohort study.

OBJECTIVES: Cervical lymph node metastases from an unknown primary tumour are a heterogeneous disease entity with various clinical features. There are many controversies regarding treatment methods and treatment response predictions. Therefore, we examined the prognostic significance of biomarkers in patients with cervical metastasis of unknown primary tumour. DESIGN: A molecular study of retrospective cohorts. SETTING: University teaching hospital. MAIN OUTCOME MEASURES: Metastatic cervical lymph nodes of 36 patients with cervical unknown primary metastasis of squamous cell carcinoma were assessed by in situ hybridisation for human papillomavirus and immunohistochemistry for p16, retinoblastoma protein (phospho-Ser780), hypoxia-inducible factor-1α, glucose transporter 1 and carbonic anhydrase 9 expression. Clinicopathological factors and biomarkers were analysed for their associations with disease-free survival and overall survival. RESULTS: Univariate analysis showed that nodal extracapsular spread was associated with poor overall survival (P = 0.049), nodal-positive retinoblastoma protein staining were significantly associated with poor outcomes of both disease-free survival (P = 0.035) and overall survival (P = 0.019), Multivariate analysis revealed that nodal positivity of retinoblastoma protein and nodal extracapsular spread were the significant predictors of overall survival (P = 0.049, hazard ratio = 6.21, 95% confidence interval = 1.01-38.35 and P = 0.037, hazard ratio = 4.34, 95% confidence interval = 1.09-17.21, respectively). CONCLUSION: The retinoblastoma protein expression of metastatic lymph nodes represents an independent prognostic indicator in patients with cervical metastasis of unknown primary tumour.