Preventive effects of dietary fucoxanthin on ultraviolet A induced photoaging in hairless mice.

BACKGROUND: Repeated exposure to ultraviolet A (UVA) irradiation, which can penetrate the epidermis and reach the dermis, is one of the major causes of skin photoaging. Photoaged skin is characterized clinically by generalized wrinkling, a dry and loose appearance, and seborrheic keratoses, along with skin barrier dysfunction. Fucoxanthin, a xanthophyll carotenoid with a specific allenic bond and 5,6-monoepoxide in its structure, has been found to serve various functions as a food supplement. In the present study, the protective effects of orally administered fucoxanthin at relatively low concentrations (0.001% and 0.01%) against UVA induced photoaging were evaluated in vivo using hairless mice. RESULTS: Oral supplementation of 0.001% fucoxanthin was sufficient for its metabolites to accumulate in the skin, thereby inhibiting pathological changes induced by UVA irradiation, including impaired skin barrier function and accelerated wrinkle formation. Analysis of gene expression revealed that dietary fucoxanthin exerted antiphotoaging effects, possibly by modulating natural moisturizing factor (NMF) synthesis, desquamation, and ceramide composition in the epidermis, and by inhibiting the UVA induced degradation of collagen fibers and inflammation in the dermis. CONCLUSION: Taken together, our data indicate the potential application of dietary fucoxanthin as a novel ingredient in nutricosmetics for skin care against photoaging. © 2024 Society of Chemical Industry.

Monocyte-to-lymphocyte ratio is a prognostic predictor for patients with non-small cell lung cancer treated with stereotactic body radiation therapy.

Background: The monocyte-to-lymphocyte ratio (MLR), a systemic inflammation biomarker, has been shown to predict patient outcomes in several types of cancer. This study aimed to determine the association between MLR and local control (LC) and cause-specific survival (CSS) rates in patients with non-small cell lung cancer (NSCLC) treated with stereotactic body radiation therapy (SBRT). Materials and methods: The median age of the 194 included participants (144 men, 50 women) was 80 (range, 50-96) years. The median follow-up period was 19 (range, 1-108) months. The LC and CSS rates were calculated using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazard regression models were used to estimate the LC and CSS rates. Results: Local recurrence was observed in 25 patients during the follow-up. Univariate Cox proportional hazards regression analysis revealed that MLR, performance status, and tumor diameter were significant factors for LC. Multivariate analysis showed MLR and tumor diameter as significant factors (p = 0.041 and 0.031, respectively). The 1- and 2-year LC rates for the lower and higher MLR groups were 97.5% and 97.5%, and 89.7% and 81.2%, respectively. During the follow-up period, 14 patients died due to NSCLC. Although MLR tended to predict CSS in univariate analysis (p = 0.086), none of the parameters was significant in predicting CSS. However, MLR as a continuous variable was a significant factor for CSS in the univariate analysis (p = 0.004). Conclusions: Our data suggest that MLR is correlated with LC and CSS rates in NSCLC patients treated with SBRT.

Biomechanical imaging biomarker during chemoradiotherapy predicts treatment response in head and neck squamous cell carcinoma.

Objective. For response-adapted adaptive radiotherapy (R-ART), promising biomarkers are needed to predict post-radiotherapy (post-RT) responses using routine clinical information obtained during RT. In this study, a patient-specific biomechanical model (BM) of the head and neck squamous cell carcinoma (HNSCC) was proposed using the pre-RT maximum standardized uptake value (SUVmax) of18F-fluorodeoxyglucose (FDG) and tumor structural changes during RT as evaluated using computed tomography (CT). In addition, we evaluated the predictive performance of BM-driven imaging biomarkers for the treatment response of patients with HNSCC who underwent concurrent chemoradiotherapy (CCRT).Approach. Patients with histologically confirmed HNSCC treated with definitive CCRT were enrolled in this study. All patients underwent CT two times as follows: before the start of RT (pre-RT) and 3 weeks after the start of RT (mid-RT). Among these patients, 67 patients who underwent positron emission tomography/CT during the pre-RT period were included in the final analysis. The locoregional control (LC), progression-free survival (PFS), and overall survival (OS) prediction performances of whole tumor stress change (TS) between pre- and mid-RT computed using BM were assessed using univariate, multivariate, and Kaplan-Meier survival curve analyses, respectively. Furthermore, performance was compared with the pre and post-RT SUVmax, tumor volume reduction rate (TVRR) during RT, and other clinical prognostic factors.Main results. For both univariate, multivariate, and survival curve analyses, the significant prognostic factors were as follows (p< 0.05): TS and TVRR for LC; TS and pre-RT FDG-SUVmaxfor PFS; and TS only for OS. In addition, for 2 year LC, PFS, and OS prediction, TS showed a comparable predictive performance to post-RT FDG-SUVmax.Significance. BM-driven TS is an effective prognostic factor for tumor treatment response after CCRT. The proposed method can be a feasible functional imaging biomarker that can be acquired during RT using only routine clinical data and may provide useful information for decision-making during R-ART.

Deep inspiration breath hold real-time tumor-tracking radiation therapy (DBRT) as a novel stereotactic body radiation therapy approach for lung tumors.

Radiotherapy with deep inspiration breath hold (DIBH) reduces doses to the lungs and organs at risk. The stability of breath holding and reproducibility of tumor location are higher during expiration than during inspiration; therefore, we developed an irradiation method combining DIBH and real-time tumor-tracking radiotherapy (RTRT) (DBRT). Nine patients were enrolled in this study. Fiducial markers were placed near tumors using bronchoscopy. Treatment planning computed tomography (CT) was performed thrice during DIBH, assisted by spirometer-based device. Each CT scan was fused using fiducial markers. Gross tumor volume (GTV) was contoured for each dataset and summed to create GTVsum; adding a 5-mm margin around GTVsum generated the planning target volume. The prescribed dose was mainly 42 Gy in four fractions. The treatment plan was created using DIBH CT (DBRT-plan), with a similar treatment plan created for expiratory CT for cases for which DBRT could not be performed (conv-plan). Vx defined as the volume of the lung received x Gy, and the mean lung dose, V20, V10, and V5 were evaluated. DBRT was completed in all patients. Mean dose, V20, and V10 were significantly lower in the DBRT-plan than in the conv-plan (all p = 0.003). Mean rates of decrease for mean dose, V20, and V10 were 14.0%, 27.6%, and 19.1%, respectively. No significant difference was observed in V5. We developed DBRT, a stereotactic body radiation therapy performed with the DIBH technique; it combines a spirometer-based breath-hold support system with an RTRT system. All patients who underwent DBRT completed the procedure without any technical or mechanical complications. This is a promising methodology that may significantly reduce lung doses.

Binding Interaction Between Lauric Acid and Cluster of Differentiation 36 Underpinned by a Fluorescence- Intensifying Assay.

Cluster of differentiation 36 (CD36) is a scavenger receptor expressed in various vertebrate cells that contains diverse ligands, including long-chain fatty acids. This receptor has recently been suggested as a captor of specific volatile odorants (e.g., aliphatic acetates) in the mammalian nasal epithelium. This study used a fluorescence-intensifying assay to produce the first evidence that lauric acid, an odorous fatty acid, directly binds to CD36. This expansion of the repertoire of volatile ligands supports potential applications for nasal CD36. Our present findings could promote future research aimed at understanding the mechanisms of fatty acid interactions with CD36.

Intra- and inter-fractional variations of tumors with fiducial markers measured using respiratory-correlated computed tomography images for respiratory gated lung stereotactic body radiation therapy.

PURPOSE: This study evaluated the intra- and inter-fractional variation of tumors with fiducial markers (FMs), relative to the tumor-FM distance, to establish how close an FM should be inserted for respiratory-gated stereotactic body radiation therapy (RG-SBRT). METHODS: Forty-five lung tumors treated with RG-SBRT were enrolled. End-expiratory computed tomography (CT) (CTplan) and four-dimensional-CT (4D-CT) scans were obtained for planning. End-expiratory CT (CTfr) scanning was performed before each fraction. The FMs were divided into two groups based on the median tumor-FM distance in the CTplan (Dp). For the intra-fractional variation, the correlations between the corresponding tumor and FM intra-fractional motions, defined as the centroid coordinates of those in each 0-90% phase, with the 50% phase of 4D-CT as the origin, were calculated in the left-right, anterior-posterior, and superior-inferior directions. Furthermore, the maximum difference in the tumor-FM distance in each phase of 4D-CT scan, based on those in the 50% phase of 4D-CT scan (Dmax), was obtained. Inter-fractional variation was defined as the maximum distance between the tumors in CTplan and CTfr, when the CT scans were fused based on each FM or vertebra. RESULTS: The median Dp was 26.1 mm. While FM intra-fractional motions were significantly and strongly correlated with the tumor intra-fractional motions in only anterior-posterior and superior-inferior directions for the Dp > 26 mm group, they were significantly and strongly correlated in all directions for the Dp ≤ 26 mm group. In all directions, Dmax values of the Dp ≤ 26 mm group were lower than those of the Dp > 26 mm group. The inter-fractional variations based on the Dp ≤ 26 mm were smaller than those on the Dp > 26 mm and on the vertebra in all directions. CONCLUSIONS: Regarding intra- and inter-fractional variation, FMs for Dp ≤ 26 mm can increase the accuracy for RG-SBRT.

Immune Checkpoint Inhibitors after Radiation Therapy Improve Overall Survival Rates in Patients with Stage IV Lung Cancer.

This exploratory and retrospective study aimed to evaluate whether there is a difference in the overall survival (OS) rates of patients with stage IV lung cancer who underwent radiation therapy (RT) depending on the presence or absence of immune checkpoint inhibitors (ICIs) and the timing of their use. Eighty patients with histologically confirmed stage IV lung cancer were enrolled, and ICIs were administered to thirty (37.5%). ICIs were administered before RT and after RT in 11 and 20 patients, respectively. The median follow-up period was 6 (range: 1-37) months. Patients treated with ICIs had significantly better OS rates than those not treated with ICIs (p < 0.001). The 6-month OS rates in patients treated with and without ICIs were 76.3% and 34.5%, respectively. The group that received ICI therapy after RT had a significantly better OS rate than the group that received ICI therapy prior to RT (6-month OS: 94.7% vs. 40.0%, p < 0.001). In the multivariate analysis, performance status (0-1 vs. 2-4) and ICI use after RT were significant factors for OS (p = 0.032 and p < 0.001, respectively). Our results suggest that ICI administration after RT may prolong the OS of patients with stage IV lung cancer.

Striped catfish (Pangasianodon hypophthalmus) exploit food sources across anaerobic decomposition- and primary photosynthetic production-based food chains.

Dietary information from aquatic organisms is instrumental in predicting biological interactions and understanding ecosystem functionality. In freshwater habitats, generalist fish species can access a diverse array of food sources from multiple food chains. These may include primary photosynthetic production and detritus derived from both oxic and anoxic decomposition. However, the exploitation of anoxic decomposition products by fish remains insufficiently explored. This study examines feeding habits of striped catfish (Pangasianodon hypophthalmus) at both adult and juvenile stages within a tropical reservoir, using stable carbon, nitrogen, and sulfur isotope ratios (δ13C, δ15N, and δ34S, respectively) and fatty acid (FA) analyses. The adult catfish exhibited higher δ15N values compared to primary consumers that feed on primary photosynthetic producers, which suggests ingestion of food sources originating from primary photosynthetic production-based food chains. On the other hand, juvenile catfish demonstrated lower δ15N values than primary consumers, correlating with low δ34S value and large proportions of bacterial FA but contained small proportions of polyunsaturated FA. This implies that juveniles utilize food sources from both anoxic decomposition and primary photosynthetic production-based food chains. Our results indicate that food chains based on anoxic decomposition can indeed contribute to the dietary sources of tropical fish species.

Assessing four-dimensional CT stress maps derived from patient-specific biomechanical models of the lung with pulmonary function test data in lung cancer patients.

OBJECTIVE: This study aims to retrospectively compare the stress map of the lung with pulmonary function test (PFT) results in lung cancer patients and to evaluate the potential of the stress map as an imaging biomarker for chronic obstructive pulmonary disease (COPD). METHODS: 25 lung cancer patients with pre-treatment four-dimensional CT (4DCT) and PFT data were retrospectively analysed. PFT metrics were used to diagnose obstructive lung disease. For each patient, forced expiratory volume in 1 s (FEV1 % predicted) and the ratio of FEV1 and forced vital capacity (FEV1/FVC) were recorded. 4DCT and biomechanical model-deformable image registration (BM-DIR) were used to obtain the lung stress map. The relationship between the mean of the total lung stress and PFT data was evaluated, and the COPD classification grade was also evaluated. RESULTS: The mean values of the total lung stress and FEV1 % predicted showed a significant strong correlation [R = 0.833, (p < 0.001)]. The mean values and FEV1/FVC showed a significant strong correlation [R = 0.805, (p < 0.001)]. For the total lung stress, the area under the curve and the optimal cut-off value were 0.94 and 510.8 Pa for the classification of normal or abnormal lung function, respectively. CONCLUSION: This study has demonstrated the potential of lung stress maps based on BM-DIR to accurately assess lung function by comparing them with PFT data. ADVANCES IN KNOWLEDGE: The derivation of stress map directly from 4DCT is novel method. The BM-DIR-based lung stress map can provide an accurate assessment of lung function.

Intestinal Absorption and Anti-Inflammatory Effects of Siphonein, a Siphonaxanthin Fatty Acid Ester from Green Algae.

Siphonein is a C19 acylated siphonaxanthin found in some edible green algae (e.g., Codium fragile and Caulerpa lentillifera). Although the content of siphonein in these green algae is similar to or higher than that of siphonaxanthin, studies of health-related biological activity of siphonein are much less than those of siphonaxanthin. Given the difference in the position of the acyl chain, one cannot infer intestinal absorption of siphonein from other general carotenoid fatty acid esters. In this study, we first investigated the intestinal absorption of siphonein using mouse and cell culture models. A small amount of siphonein was detected in the plasma of treated mice, and its concentration was higher than that of siphonaxanthin (i.e., the hydrolyzed product of ingested siphonein) from 1 to 6 h after administration. Pharmacological inhibition tests with differentiated Caco-2 cells showed that Nieman-Pick C1-like 1-mediated facilitated diffusion was involved in the cellular uptake of siphonein. These results indicate that, unlike general carotenoid fatty acid esters, siphonein can be absorbed without hydrolysis. We also evaluated the anti-inflammatory effect of siphonein in differentiated Caco-2 cells. Siphonein pretreatment modulated lipopolysaccharide-induced cellular lipidome alterations and suppressed mRNA expression of proinflammatory chemokines, CXCL8 protein release, and activation of NF-κB. This study provides new insights into the absorption processes of carotenoids and shows the anti-inflammatory effect of siphonein for the first time.

Differences in Radiosensitivity According to EGFR Mutation Status in Non-Small Cell Lung Cancer: A Clinical and In Vitro Study.

Unlike drug selection, radiation parameters (field, dose) are not based on driver gene mutations in patients with metastatic non-small cell lung cancer (NSCLC). This study aimed to compare radiosensitivity in NSCLC with and without EGFR driver gene mutations using clinical and in vitro data. The clinical study included 42 patients who underwent whole-brain radiotherapy for brain metastases from NSCLC; of these, 13 patients had EGFR mutation-positive tumors. The Kaplan-Meier method was used to calculate the cranial control rate without intracranial recurrence. In the in vitro study, colony formation and double-strand DNA breaks were examined in two EGFR mutation-negative and three EGFR mutation-positive NSCLC-derived cell lines. Colony formation was assessed 14 days after irradiation with 0 (control), 2, 4, or 8 Gy. DNA double-strand breaks were evaluated 0.5 and 24 h after irradiation. EGFR mutation-positive patients had a significantly better cranial control rates than EGFR mutation-negative patients (p = 0.021). EGFR mutation-positive cells formed significantly fewer colonies after irradiation with 2 or 4 Gy than EGFR mutation-negative cells (p = 0.002, respectively) and had significantly more DNA double-strand breaks at 24 h after irradiation (p < 0.001). Both clinical and in vitro data suggest that EGFR mutation-positive NSCLC is radiosensitive.

Gly-Pro protects normal human dermal fibroblasts from UVA-induced damages via MAPK-NF-κB signaling pathway.

Photoaging is characterized by skin dysfunction and wrinkle formation predominantly caused by chronic exposure to ultraviolet (UV) irradiation. Collagen peptides are well-recognized as nutritional supplements for enhancing skin health. Gly-Pro, a dipeptide found in collagen as a major repetitive sequence, is considered a prospect collagen peptide derivative that displays anti-photoaging potential. Herein, we evaluated the photoprotective effects of Gly-Pro in normal human dermal fibroblasts (NHDFs). Pretreatment by Gly-Pro at a concentration of 0.1 µM inhibited UVA-driven generation of reactive oxygen species (ROS) in NHDFs and attenuated UVA-induced changes in mRNA expression and activation of proteins of the MAPK-NF-κB signaling pathway. Meanwhile, Pro-Gly and cyclo(-Gly-Pro), two dipeptides that are structurally similar to Gly-Pro, depicted less anti-photoaging effects against UVA irradiation. Collectively, our data suggests that Gly-Pro has potential as a novel ingredient in nutricosmetic products for skincare and anti-photoaging.

Water-Based Solid-Phase Peptide Synthesis without Hydroxy Side Chain Protection.

The development of protecting group-free synthesis has come to the forefront this century, as there is an increasing need to switch to greener synthetic methods. In peptide synthesis, a strategy of maximum protection offers the most efficient synthetic pathway, but minimal side chain protection is more favorable in terms of green chemistry. Here, we describe solid-phase peptide synthesis (SPPS) without hydroxy side chain protection based on an aqueous microwave (MW)-assisted method. First, we investigated the extent of O-acylation of the hydroxy side chain of Ser, Thr, and Tyr occurring in our method, which uses 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride. Under aqueous MW-assisted conditions, the coupling reaction proceeded efficiently without substantial O-acylation. Next, we applied the aqueous synthetic protocol without hydroxy side chain protection to synthesis of a laminin-related peptide, H-Tyr-Ile-Gly-Ser-Arg-NH2. HPLC analysis of the crude peptide revealed a single peak, suggesting the absence of side reactions including O-acylation and racemization. We also succeeded in synthesizing a difficult peptide sequence, acyl carrier protein (65-74) peptide, by aqueous SPPS without hydroxy or carboxamide side chain protection. Based on the eighth criterion of the 12 principles of green chemistry, namely, "reduce derivatives", our approach without hydroxy side chain protection will provide a greener peptide synthesis.

Early secretory pathway-resident Zn transporter proteins contribute to cellular sphingolipid metabolism through activation of sphingomyelin phosphodiesterase 1.

Sphingomyelin phosphodiesterase 1 (SMPD1) converts sphingomyelin into ceramide and phosphocholine; hence, loss of SMPD1 function causes abnormal accumulation of sphingomyelin in lysosomes, which results in the lipid-storage disorder Niemann-Pick disease (types A and B). SMPD1 activity is dependent on zinc, which is coordinated at the active site of the enzyme, and although SMPD1 has been suggested to acquire zinc at the sites where the enzyme is localized, precisely how SMPD1 acquires zinc remains to be clarified. Here, we addressed this using a gene-disruption/reexpression strategy. Our results revealed that Zn transporter 5 (ZNT5)-ZNT6 heterodimers and ZNT7 homodimers, which localize in the compartments of the early secretory pathway, play essential roles in SMPD1 activation. Both ZNT complexes contribute to cellular sphingolipid metabolism by activating SMPD1 because cells lacking the functions of the two complexes exhibited a reduced ceramide to sphingomyelin content ratio in terms of their dominant molecular species and an increase in the sphingomyelin content in terms of three minor species. Moreover, mutant cells contained multilamellar body-like structures, indicative of membrane stacking and accumulation, in the cytoplasm. These findings provide novel insights into the molecular mechanism underlying the activation of SMPD1, a key enzyme in sphingolipid metabolism.

Predicting programmed death-ligand 1 expression level in non-small cell lung cancer using a combination of peritumoral and intratumoral radiomic features on computed tomography.

In this study, we investigated the possibility of predicting expression levels of programmed death-ligand 1 (PD-L1) using radiomic features of intratumoral and peritumoral tumors on computed tomography (CT) images. We retrospectively analyzed 161 patients with non-small cell lung cancer. We extracted radiomic features for intratumoral and peritumoral regions on CT images. The null importance, least absolute shrinkage, and selection operator model were used to select the optimized feature subset to build the prediction models for the PD-L1 expression level. LightGBM with five-fold cross-validation was used to construct the prediction model and evaluate the receiver operating characteristics. The corresponding area under the curve (AUC) was calculated for the training and testing cohorts. The proportion of ambiguously clustered pairs was calculated based on consensus clustering to evaluate the validity of the selected features. In addition, Radscore was calculated for the training and test cohorts. For expression level of PD-L1 above 1%, prediction models that included radiomic features from the intratumoral region and a combination of radiomic features from intratumoral and peritumoral regions yielded an AUC of 0.83 and 0.87 and 0.64 and 0.74 in the training and test cohorts, respectively. In contrast, the models above 50% prediction yielded an AUC of 0.80, 0.97, and 0.74, 0.83, respectively. The selected features were divided into two subgroups based on PD-L1 expression levels≥50% or≥1%. Radscore was statistically higher for subgroup one than subgroup two when radiomic features for intratumoral and peritumoral regions were combined. We constructed a predictive model for PD-L1 expression level using CT images. The model using a combination of intratumoral and peritumoral radiomic features had a higher accuracy than the model with only intratumoral radiomic features.

Oral supplementation of sea cucumber and its hydrolysate mitigates ultraviolet A-induced photoaging in hairless mice.

BACKGROUND: Chronic exposure to ultraviolet (UV) radiation promotes skin photoaging, which is clinically characterized by dryness, laxity, and wrinkling. Sea cucumber (Stichopus japonicus) (SC) is a marine organism with culinary and medicinal applications, especially in Asian countries. It is also a potential nutraceutical as it exhibits bioactive effects, such as antioxidant, antitumor, and anticancer activity. This study examined the effects of SC and its hydrolysate (SCH) on ultraviolet A (UVA) induced skin barrier function and wrinkle formation using hairless mice. RESULTS: Ultraviolet A significantly induced transepidermal water loss and wrinkle formation, which were significantly mitigated upon oral administration of SC and SCH. Sea cucumber also mitigated the UVA-induced downregulation of epidermal natural moisturizing factors and the upregulation of Aqp3, Mmp13, Tnfa, and Il6 mRNA levels in the mouse skin. CONCLUSION: Taken together, these results suggest that dietary SC and SCH exert anti-photoaging effects by modulating filaggrin synthesis and desquamation in the epidermis and regulating the NF-κB pathway in the skin. Our research indicates that SC and SCH have potential applications in nutricosmetics for photoaging. © 2021 Society of Chemical Industry.

Multivariate Analysis Reveals That Unsubstituted ß-Ring and C8-Keto Structures Are Important Factors for Anti-Inflammatory Activity of Carotenoids.

Carotenoids are natural lipophilic pigments with substantial health benefits. Numerous studies have demonstrated the anti-inflammatory activities of carotenoids, especially toward lipopolysaccharide-induced inflammatory responses. As such, there are few reports on the evaluation and comparison of the anti-inflammatory activities of carotenoids against inflammation induced by other stimuli. In this study, we used pathogen-associated molecular patterns, proinflammatory cytokines, degenerated proteins, and chemical irritants as inflammatory inducers to evaluate the anti-inflammatory activities of eight different carotenoids. Each carotenoid showed characteristic anti-inflammatory activities; thus, we conducted a multivariate analysis to clarify the differences among them. Unsubstituted ß-ring (i.e., provitamin A) and C8-keto structures of carotenoids were found to be crucial for their inhibitory effects on the activation of nuclear factor-kappa B and interferon regulatory factors, respectively. Furthermore, we found that ß-carotene and echinenone treatment increased intracellular retinoid levels in monocytes and that the retinoids showed the similar activities to ß-carotene and echinenone. Taken together, the intake of both provitamin A and C8-keto carotenoids (e.g., siphonaxanthin and fucoxanthin) might be effective in improving the inflammatory status of individuals. A multivariate analysis of anti-inflammatory activities is a useful method for characterizing anti-inflammatory compounds.

Anemia is a Prognostic Factor for Overall Survival Rate in Patients with Non-Small Cell Lung Cancer Treated with Stereotactic Body Radiation Therapy.

PURPOSE: Anemia has been associated with poor prognosis in patients with cancer across several cancer types. It has been identified as a prognostic factor in patients with non-small cell lung cancer (NSCLC) who have undergone surgery or chemoradiotherapy. However, there are only a few reports that have evaluated the prognostic significance of anemia in patients with NSCLC undergoing stereotactic body radiation therapy (SBRT). PATIENTS AND METHODS: A total of 77 patients were enrolled in this study. The pretreatment hemoglobin (Hb) levels, within 2 weeks before SBRT, were available for all patients. The median age of the participants (56 men, 21 women) was 80 (range, 50-90) years. The median Hb level was 12.8 (range, 7.8-18.3) g/dL. The median follow-up period was 24 (range, 1-87) months. RESULTS: Local recurrence was observed in 8 (10.4%) cases during the follow-up period. The 1- and 2-year local control (LC) rates were 94.8% and 86.4%, respectively. Seventeen (22.1%) patients died during the follow-up period. The 1- and 2-year overall survival (OS) rates were 93.1% and 85.2%, respectively. Univariate analysis identified anemia and body mass index as significant prognostic factors for predicting OS. On multivariate analysis, anemia was confirmed to be the only significant factor (p = 0.02469). CONCLUSION: Our data suggest that anemia is a prognostic factor for predicting the OS rate in patients with early-stage NSCLC treated with SBRT.

Assessment of direct binding interaction between CD36 and its potential lipid ligands using a peptide mimic of the receptor labeled with a fluorophore.

Cluster of differentiation 36 (CD36) is a cell-surface receptor that recognizes diverse substances. We have presented indirect evidence that a short segment of the receptor comprising amino acids 149-168 contains a site for binding of its lipid ligands (e.g., distinct fatty acids and aldehydes). However, experimental support for their direct interactions is yet to be achieved. For this, we devised a fluorescence intensity assay, where a synthetic peptide consisting of CD36 amino acids 149-168 labeled with fluorescein isothiocyanate (FITC-CD36149-168) and its variant peptides were used as positive and negative probes, respectively. First, we obtained results indicating that 1-palmitoyl-2-(5-keto-6-octenedioyl)phosphatidylcholine (an established CD36 ligand) but not 1-palmitoyl-2-arachidonyl-phosphatidylcholine (a non-ligand of the receptor) bound in a saturable and specific manner to FITC-CD36149-168. Strikingly, the assay allowed us to provide the first evidence supporting direct and specific binding between the CD36 segment and fatty aldehydes (e.g., Z-11-hexadecenal). However, this method failed to illustrate specific interactions of the segment with fatty acids, such as oleic acid. Nonetheless, our findings offer further insight into the biologically relevant ligands and the role of CD36. In addition, we suggest that this fluorescence-based technique provides a convenient means to evaluate protein (peptide)-lipid interactions.