Colorimetric and ECL dual-mode aptasensor for smartphone-based onsite sensitive detection of aflatoxin B1 in combination with ZnO@MWCNTs/g-C3N4 nanosheets and CuO@CuPt nanocomposites.

The development of dual-mode strategies with superior sensitivity and accuracy have garnered increasing attention for researchers in Aflatoxin B1 (AFB1) analysis. Herein, a colorimetric-electrochemiluminescence (ECL) dual-mode biosensor was constructed for onsite and ultrasensitive determination of AFB1. The multi-wall carbon nanotubes (MWCNTs) were integrated with the ZnO metal organic frameworks (MOFs) to accelerate the electron transfer and boost the ECL intensity of g-C3N4 nanoemitters. Through the aptamer-based DNA sandwich assay, the CuO@CuPt nanocomposites were introduced onto the electrode and acted as the dual functional signal nanoprobes. Due to the good spectrum overlap between the CuO@CuPt nanoprobes and g-C3N4 nanosheets, ECL signal could be efficiently quenched. Additionally, the CuO@CuPt nanoprobes show superior catalytic properties towards the TMB and H2O2 colorimetric reactions, and an obvious color alteration from colorless to blue can be observed using the smartphone. Under optimized conditions, a sensitive and accurate dual-mode analysis of the AFB1 was accomplished with the colorimetric detection limit of 3.26 fg/mL and ECL detection limit of 0.971 fg/mL (S/N = 3). This study combines innovative nanomaterial properties of ZnO@MWCNTs, g-C3N4 and CuO@CuPt for ultrasensitive dual-mode detection, which offers new opportunities for the innovative engineering of the dual-mode sensors and demonstrates significant potential in food safety analysis.

Synergetic surface enhancement of quantum dots-based electrochemiluminescence with photonic crystal light scattering and metal surface plasmon resonance for sensitive bioanalysis.

Noble metal nanostructures and photonic crystals (PhCs) have been widely investigated as substrates for constructing surface enhanced electrochemiluminescence (SE-ECL) biosensors. However, their applications are hindered by the limited enhancement intensity of surface plasmon resonance (SPR) and an incomplete mechanism for the photonic enhancement effect. Hence, developing a novel SE-ECL strategy with better signal enhanced capability and enriching our understanding of the intrinsic mechanisms for efficient bioanalysis is extremely urgent. Here, a synergistic SE-ECL strategy was developed for the sensitive determination of prostate specific antigen (PSA) protein. The randomly arranged polystyrene (r-PS) spheres and PS PhC arrays were applied to enhance the ECL emission of cadmium sulfide quantum dots (CdS QDs) and the results suggested that the PhC arrays displayed superior intensity (0.22) than the r-PS interface (0.10). Au nanoparticles (NPs) were introduced onto the two kinds of surfaces and further boosted the ECL intensity. According to the ECL measurements, Au NPs modified at the r-PS surface exhibited only a slight increase (0.13), while the PhC arrays showed approximately 5-fold enhancement (0.92), benefiting from the synergistic enhancement. The finite-difference time-domain (FDTD) simulation indicated that the ECL enhancement was ascribed to the coupled electromagnetic (EM) field at the surfaces of PS PhCs and Au NPs. The SE-ECL could achieve a detection range from 1 pg/mL to 1 µg/mL with a detection limit of 0.41 pg/mL (S/N = 3). This study provides the first combination of PhC arrays and metal surface plasmon nanostructure for the synergetic enhancement of SE-ECL systems. It opens a new avenue for the rational design of advanced ECL biosensors and shows great perspective for clinical diagnosis.

AIE fluorogen-based oxidase-like fluorescence nanozyme-integrated smartphone for monitoring the freshness authenticity of soy products.

Food safety concerns about the authenticity of soy product freshness have increased due to high demand from public. Developing an accurate and convenient monitoring method for freshness authenticity is crucial for safeguarding food safety. From this motive, this study employed PtPd NPs to encapsulate tetraphenylethylene (TPE) for engineering an AIE-based fluorescent nanozyme (PtPd NPs@TPE) with oxidase-like activity, achieving the ratiometric fluorescence monitoring of putrescine (PUT) to judge the freshness authenticity of soy products. In this design, PUT acted as an antioxidant and inhibited the oxidation process of PtPd NPs@TPE to o-phenylenediamine (OPD), leading to the reduction of oxidative product 2,3-diaminophenothiazine (DAP) alone with the weaken of yellow fluorescence from DAP at 552 nm and bright of bule fluorescence from PtPd NPs@TPE at 442 nm. On this basis, a ratiometric fluorescence strategy integrated with smartphone-based sensor was developed for PUT with acceptable results to combat food freshness fraud of soy products.

Period 2 Suppresses the Malignant Cellular Behaviors of Colorectal Cancer Through the Epithelial-Mesenchymal Transformation Process.

INTRODUCTION: The PER2 (Period circadian regulator 2) gene is related to the circadian clock, and it has been deemed as a suppressor gene in osteosarcoma and lung carcinoma. However, the part of PER2 in CRC (colorectal cancer) needs to be further determined. METHODS: First, we collected clinical samples to detect PER2 expression in CRC. Then, we used cell transfection to knock down PER2 expression in CRC cell lines and performed a series of functional experiments to elucidate the effects of PER2 on CRC cells. We next verified whether PER2 affects the epithelial-mesenchymal transformation (EMT) process in CRC by conducting quantitative real-time PCR and western blotting. RESULTS: In the research, we revealed that the expression of PER2 decreased in CRC clinical samples. In addition, knocking down PER2 expression caused CRC cells to acquire malignant biological features. Finally, we found that PER2 knockdown may activate the Snail/Slug axis through inhibiting p53, therefore promote the activation of the EMT pathway. CONCLUSION: In conclusion, low PER2 expression reinforces migration and activates EMT in CRC, suggesting that PER2 is closely related to CRC development and could be used as a potential treatment site in the clinic.

Identification of crucial genes of pyrimidine metabolism as biomarkers for gastric cancer prognosis.

BACKGROUND: Metabolic reprogramming has been reported in various kinds of cancers and is related to clinical prognosis, but the prognostic role of pyrimidine metabolism in gastric cancer (GC) remains unclear. METHODS: Here, we employed DEG analysis to detect the differentially expressed genes (DEGs) in pyrimidine metabolic signaling pathway and used univariate Cox analysis, Lasso-penalizes Cox regression analysis, Kaplan-Meier survival analysis, univariate and multivariate Cox regression analysis to explore their prognostic roles in GC. The DEGs were experimentally validated in GC cells and clinical samples by quantitative real-time PCR. RESULTS: Through DEG analysis, we found NT5E, DPYS and UPP1 these three genes are highly expressed in GC. This conclusion has also been verified in GC cells and clinical samples. A prognostic risk model was established according to these three DEGs by Univariate Cox analysis and Lasso-penalizes Cox regression analysis. Kaplan-Meier survival analysis suggested that patient cohorts with high risk score undertook a lower overall survival rate than those with low risk score. Stratified survival analysis, Univariate and multivariate Cox regression analysis of this model confirmed that it is a reliable and independent clinical factor. Therefore, we made nomograms to visually depict the survival rate of GC patients according to some important clinical factors including our risk model. CONCLUSION: In a word, our research found that pyrimidine metabolism is dysregulated in GC and established a prognostic model of GC based on genes differentially expressed in pyrimidine metabolism.

Altered Patterns of Functional Connectivity and Causal Connectivity in Salience Subnetwork of Subjective Cognitive Decline and Amnestic Mild Cognitive Impairment.

The subjective cognitive decline (SCD) may last for decades prior to the onset of dementia and has been proposed as a risk population for development to amnestic mild cognitive impairment (aMCI) and Alzheimer disease (AD). Disruptions of functional connectivity and causal connectivity (CC) in the salience network (SN) are generally perceived as prominent hallmarks of the preclinical AD. Nevertheless, the alterations in anterior SN (aSN), and posterior SN (pSN) remain unclear. Here, we hypothesized that both the functional connectivity (FC) and CC of the SN subnetworks, comprising aSN and pSN, were distinct disruptive in the SCD and aMCI. We utilized resting-state functional magnetic resonance imaging to investigate the altered FC and CC of the SN subnetworks in 28 healthy controls, 23 SCD subjects, and 29 aMCI subjects. In terms of altered patterns of FC in SN subnetworks, aSN connected to the whole brain was significantly increased in the left orbital superior frontal gyrus, left insula lobule, right caudate lobule, and left rolandic operculum gyrus (ROG), whereas decreased FC was found in the left cerebellum superior lobule and left middle temporal gyrus when compared with the HC group. Notably, no prominent statistical differences were obtained in pSN. For altered patterns of CC in SN subnetworks, compared to the HC group, the aberrant connections in aMCI group were separately involved in the right cerebellum inferior lobule (CIL), right supplementary motor area (SMA), and left ROG, whereas the SCD group exhibited more regions of aberrant connection, comprising the right superior parietal lobule, right CIL, left inferior parietal lobule, left post-central gyrus (PG), and right angular gyrus. Especially, SCD group showed increased CC in the right CIL and left PG, whereas the aMCI group showed decreased CC in the left pre-cuneus, corpus callosum, and right SMA when compared to the SCD group. Collectively, our results suggest that analyzing the altered FC and CC observed in SN subnetworks, served as impressible neuroimaging biomarkers, may supply novel insights for designing preclinical interventions in the preclinical stages of AD.

Metallic Inverse Opals: An Electrochemiluminescence enhanced Substrate for Sensitive Bioanalysis.

Here, we proposed a novel local surface plasmon resonance (LSPR) enhanced ECL strategy based on the metallic inverse opals and Ru(bpy)32+-doped silica nanoparticles (RuSi NPs). Gold inverse opals (GIOs), as a plasmonic array, could interact with the ECL of RuSi NPs and excite the electromagnetic (EM) field at the gold surface. The triggered EM field could enhance the ECL emission of RuSi NPs. We compared the electrochemical and ECL performances of RuSi NPs modified on the gold electrodes with different surface morphologies and found that the ECL emission of RuSi NPs patterned at the inner surface of GIOs exhibited the highest intensity. The finite-difference time-domain (FDTD) simulations indicated that the EM field was related to the surface morphology of the metallic nanostructure, and the highest EM field was observed at the inner surface of the GIOs. Because of the superior ECL performances, the inner surfaces of GIOs were developed for nucleic acid detection with a detection limit of 3.3 fM (S/N = 3), which shows great promise for bioanalysis.

Recent advances of ratiometric electrochemiluminescence biosensors.

Ratiometric electrochemiluminescence (ECL) assays have been widely applied in biosensing because of eliminated outside interferences and improved reliability in detection. In order to construct ratiometric ECL biosensors with high sensitivity and reliability, it is critical to find two signal emitters with suitable applied potentials or emission wavelengths. This review aims to discuss recent advances and trends of ratiometric ECL biosensors in terms of ECL materials and corresponding ratiometric sensing approaches. We focus on four types of ratiometric ECL biosensors based on particular ECL materials and ratiometric sensing strategies.

The double inhibition of PDK1 and STAT3-Y705 prevents liver metastasis in colorectal cancer.

As a key glycolysis enzyme, the significance of pyruvate dehydrogenase kinase 1 (PDK1) in the development of colorectal cancer (CRC) remains unknown. This study revealed that the prognosis of CRC patients with high levels of PDK1 was poor, and PDK1 knockdown significantly reduced liver metastasis of CRC in both nude mice and immune competent BALB/C mice. When combined with cryptotanshinone (CPT), an inhibitor of STAT3-p-Y705, the liver metastasis was further inhibited. PDK1 knockdown obviously increased reactive oxygen species level in anoikis conditions and subsequently resulted in an elevated anoikis, but the combination of PDK1 knockdown and CPT showed a reduced effect on anoikis. Based on this discrepancy, the adherence ability of CRC cells to matrix protein fibronectin was further detected. It showed that PDK1 knockdown significantly decreased the adherence of CRC cells to fibronectin when combined with CPT. These results suggest that inhibition of PDK1 can decrease the surviving CRC cells in blood circulation via up-regulation of anoikis, and inhibition of STAT3-p-Y705 can prevent it to settle down on the liver premetastatic niche, which ultimately reduces liver metastasis.

Three-level spaser for next-generation luminescent nanoprobe.

The development of modern biological and medical science highly depends on advanced luminescent probes. Current probes typically have wide emission spectra of 30 to 100 nm, which limits the number of resolvable colors that are simultaneously labeled on samples. Spasers, the abbreviation for surface plasmon lasers, have ultranarrow lasing spectra by stimulated light amplification in the plasmon nanocavity. However, high threshold (>102 mJ cm-2) and short lasing lifetime (approximately picoseconds to nanoseconds) still remain obstacles for current two-level spaser systems. We demonstrated a new type of a three-level spaser using triplet-state electrons. By prolonging the upper state lifetime and controlling the energy transfer, high gain compensation was generated. This probe, named delayed spasing dots (dsDs), about 50 to 60 nm in size, exhibited a spectral linewidth of ~3 nm, an ultralow threshold of ~1 mJ cm-2, and a delayed lasing lifetime of ~102 µs. As the first experimental realization of the three-level spaser system, our results suggested a general strategy to tune the spasing threshold and dynamics by engineering the energy level of the gain medium and the energy transfer process. These dsDs have the potential to become new-generation luminescent probes for super-multiplex biological analysis without disturbance from short lifetime background emission.

Ultrasmall Nanopipette: Toward Continuous Monitoring of Redox Metabolism at Subcellular Level.

Ionic current rectification (ICR) based nanopipettes allow accurate monitoring of cellular behavior in single living cells. Herein, we proposed a 30 nm nanopipette functionalized with G-quadruplex DNAzyme as an efficient biomimetic recognizer for ROS generation at subcellular level via the changes of current-voltage relationship. Taking advantages of the ultra-small tip, the nanopipette could penetrate into a single living cell repeatedly or keep measuring for a long time without compromising the cellular functions. Coupled with precision nanopositioning system, generation of ROS in mitochondria in response to cell inflammation was determined with high spatial resolution. Meanwhile, the changes of aerobic metabolism in different cell lines under drug-induced oxidative stress were monitored continuously. We believe that the ICR-nanopipette could be developed as a powerful approach for the study of cellular activities via electrochemical imaging in living cells.

Electrochemiluminescence Energy Resonance Transfer System between RuSi Nanoparticles and Hollow Au Nanocages for Nucleic Acid Detection.

This paper describes an electrochemiluminescence resonance energy transfer (ECL-RET) system using Ru(bpy)32+-doped silica nanoparticles (RuSi NPs) as the ECL donor and hollow Au nanocages as the ECL acceptor. Tetrahedron DNA (TD) was used to construct the biosensing interface and control the distance (4.8 nm) between the ECL donor-acceptor pairs. The surface plasmon resonance (SPR) nanostructures, Au nanocages were assembled via the hairpin based sandwich assay. Due to the well overlap between the plasmon absorption spectrum of Au nanocages (628 nm) and the ECL emission spectrum of RuSi NPs (620 nm), high efficient energy transfer could occur. Subsequent cyclic DNA amplification further increased the binding amount of Au nanocages. Since the ECL inhibition is closely related with the binding amount of Au nanocages, a general "signal-off" ECL bioassay could thus be tailored with high sensitivity. At the optimized conditions, this ECL-RET system performed well with great stability and repeatability for nucleic acid detection in the range from 1.0 fM to 10 pM. This work manifested the great promise of hollow Au nanocages for an ECL-RET biosensor that to the best of our knowledge has not been reported. We believe that it could inspire more interest in the design and development of numerous other SPR nanostructures for advanced ECL-RET biosensors.

Visual electrochemiluminescence ratiometry on bipolar electrode for bioanalysis.

In this work, we developed a visual ECL ratiometry on a closed bipolar electrode (BPE) for the detection of prostate specific antigen (PSA), prostate cancer biomarker. High efficient CdTe QDs was synthesized which emitted visualized red light at BPE cathode. Integrating with the anodic ECL emitters, luminol, visual emission of red-blue ratiometric ECL was achieved in BPE array chips. As a sensing probe, Au NRs nanocomposite was assembled on the surface of the cathode and acted as both the quencher of the CdTe QDs ECL and the promoter of the luminol ECL. After incubated with PSA, the Au NRs nanocomposite was peeled off from the electrode surface due to the specific recognition between PSA and aptamer. Consequently, the cathode ECL partly recovered and the anode ECL turned off. By measuring the ratio of visual ECL intensity at two poles of BPE, sensitive detection of PSA was achieved with a linear range from 1.0ng/mL to 1.0µg/mL and detection limit of 0.5ng/mL (S/N=3). This strategy combining the BPE-ECL and visual ratiometry provided an accurate and intrinsic way for the sensing of PSA and showed good perspective in the clinical diagnosis.

Effect of CyberKnife stereotactic body radiation therapy for hepatocellular carcinoma on hepatic toxicity.

OBJECTIVE: To evaluate the safety of CyberKnife stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma (HCC) patients and identify the treatment-related risk factors of hepatic toxicity. MATERIALS AND METHODS: One hundred and four HCC patients treated with CyberKnife SBRT were included in this study between August 2009 and December 2012. The average dose of prescribed radiation was 42.81±4.78 Gy (28-55 Gy) with the average fraction size of 8-16 Gy to the planning target volume. The average fractions were 3.31±0.81 (2-6 fractions). Response rates were determined, and the Child-Pugh (CP) score and class following CyberKnife SBRT were obtained to evaluate hepatic toxicity. RESULTS: Seventeen patients experienced progression in CP class and 24 patients experienced CTCAE V. 4.0 grade 2-3 hepatic toxicity during the five-month follow-up period, while no patient experienced grade 4 liver toxicity. Multivariate analysis indicated that only V25 was an independent factor in grade 2-3 hepatic toxicity (P=0.029, <0.05). Radiation-induced hepatic toxicity (RIHT), defined as an increase of at least two points within three months following CyberKnife SBRT, occurred in 13 of the 104 patients (13/104, 12.5%), and only the normal liver tissue was found to be associated with RIHT (P=0.008, <0.05). CONCLUSION: CyberKnife SBRT is a feasible and safe treatment for HCC with regard to hepatic toxicity, while V25 and normal liver volume may be an independent factor of grade 2-3 hepatic toxicity and RIHT, respectively.

Spatial-resolved electrochemiluminescence ratiometry based on bipolar electrode for bioanalysis.

Herein, a spatial-resolved electrochemiluminescene (ECL) ratiometry based on a closed biopolar electrode (BPE) is reported for the highly sensitive detection of prostate specific antigen (PSA). Au@g-C3N4 NCs as one ECL emitter were firstly coated on the cathode of BPE, while the anode of the BPE served for calibration via another ECL substance, Ru(bpy)3(2+). The electroneutrality across the BPE makes the reactions on each pole of BPE electrically coupled. Thus one electrochemical sensing reaction at one pole of BPE could be quantified at both ends. A composite, Pt-PAMAM-DNAzyme was assembled on the surface of cathode via DNA hybridization between probe DNA and PSA aptamer. It acted as an ECL quencher of g-C3N4 via resonance energy transfer (RET) and catalyzing the reduction of O2, the co-reactant of g-C3N4. Meanwhile, it could promote the ECL of Ru(bpy)3(2+) at anode, since the catalytic reduction of O2 at the cathode increased the faradiac current flowing through the BPE. Based on this signal composite, an ECL "off-on" phenomenon was observed at the cathode, after Pt-PAMAM-DNAzyme was "peeled off" by PSA. Conversely, at the anode, an "on-off" ECL changing was obtained. Therefore, a sensitive ratiometry for PSA detection was achieved with a linear range from 0.10 to 200ng/mL. Since the two ECL emitters were physically separated, the ratiometric system was relatively simple and neither optical filters nor spectrometer were required. The strategy combining the ECL ratiometry and BPE broadens the applications of BPE-ECL and shows good perspective in clinical application.

p53 Is a Direct Transcriptional Repressor of Keratin 17: Lessons from a Rat Model of Radiation Dermatitis.

The intermediate filament protein keratin 17 (Krt17) shows highly dynamic and inducible expression in skin physiology and pathology. Because Krt17 exerts physiologically important functions beyond providing structural stability to keratinocytes whereas abnormal Krt17 expression is a key feature of dermatoses such as psoriasis and pachyonychia congenita, the currently unclear regulation of Krt17 expression needs to be better understood. Using a rat model of radiation dermatitis, we report here that Krt17 expression initially is down-regulated but later is strongly up-regulated by ionizing radiation. The early down-regulation correlates with the activation of p53 signaling. Deletion of p53 abolishes the initial down-regulation but not its subsequent up-regulation, suggesting that p53 represses Krt17 transcription. Because previous work reported up-regulation of Krt17 by ultraviolet irradiation, which also activates p53 signaling, the effect of ultraviolet radiation was reexamined. This revealed that the initial down-regulation of Krt17 is conserved, but the up-regulation comes much faster. Chromatin immunoprecipitation analysis in vivo and electromobility shift assay in vitro identified two p53-binding sites in the promoter region of Krt17. Thus, p53 operates as a direct Krt17 repressor, which invites therapeutic targeting in dermatoses characterized by excessive Krt17 expression.

Efficacy and toxicity of nimotuzumab combined with radiotherapy in elderly patients with esophageal squamous cell carcinoma.

This study was conducted to assess the efficacy and toxicity of nimotuzumab combined with radiotherapy (RT) in elderly patients with esophageal squamous cell carcinoma. The clinical data of 16 esophageal squamous cell carcinoma patients, aged >70 years, who were initially treated with nimotuzumab combined with RT, were collected and retrospectively reviewed. The overall response and treatment toxicity were analyzed using SPSS software. All the patients completed the treatment schedule. The response to treatment was assessed at treatment completion and reassessed after 1-2 months: 1 patient achieved complete response (CR), 10 patients achieved partial response (PR), 4 patients exhibited stable disease and 1 patient developed disease progression and succumbed to radiation pneumonitis (RP) 1 month later. The overall response rate (CR+PR) was 68.8%. All 16 patients experienced grade 1-2 radiation esophagitis; no grade 3-4 toxicities were reported. There was one case of treatment-related mortality due to RP during the study. One patient developed a rash on the forearm. No hematological, gastrointestinal, hepatic or renal toxicities were observed. In conclusion, the toxicity of combined nimotuzumab with RT in elderly patients with esophageal cancer was tolerable. However, due to limitations associated with the retrospective nature of this study, the limited number of enrolled cases and the epidermal growth factor receptor expression determination prior to treatment, the efficacy of this treatment modality requires further investigation.

The efficacy and toxicities of combined lobaplatin with paclitaxel as a first-line chemotherapy for advanced esophageal squamous cell carcinoma.

BACKGROUND: To assess the efficacy and toxicities of combined lobaplatin with paclitaxel (LP) as a first line chemotherapy in esophageal cancer. METHODS: The clinical data of 45 patients with esophageal squamous cell carcinoma treated initially with lobaplatin-paclitaxel chemotherapy were collected and reviewed retrospectively. The overall response, treatment toxicities and dysphagia relief were analyzed with SPSS software. RESULTS: The overall response rate was 42.2%, with 1 patient (2.2%) showing complete remission, 18 patients (40.0%) with partial remission, 19 (42.2%) with stable disease (SD), and 7 (15.6%) with progressive disease, respectively. The most common hematological toxicity was leucopenia with grade 0, I, II, III and IV in 16 (35.6%), 10 (22.2%), 11 (24.4%), 7 (15.6%), and 1 patient (2.2%), respectively. Thirty-seven patients (82.2%) experienced grade I-II nausea/vomiting without grade III-IV instances occurring. Four patients (8.9%) experienced grade I hepatotoxicity. No nephrotoxicity was observed. Five in thirteen patients treated with concurrent chemoradiotherapy (CRT) suffered severe radiation pneumonitis. The dysphagia resolved or improved in 32 patients (71%). CONCLUSIONS: Lobaplatin-paclitaxel showed a significant antitumor effect to squamous esophageal cancer with manageable toxicities. Limitation of the surveillance time and the retrospective nature, the effect that based on these data formal prospective trials appear warranted and are needed prior to routine first line use of this regimen.

Is the irradiated small bowel volume still a predictor for acute lower gastrointestinal toxicity during preoperative concurrent chemo-radiotherapy for rectal cancer when using intensity-modulated radiation therapy?

BACKGROUND: The small bowel (SB) represents the most important dose-limiting structure in pelvic radiotherapy (RT). However, we observed that the majority of rectal cancer patients who received preoperative pelvic intensity modulated RT (IMRT) developed acute tenesmus without watery diarrhea. The objective of this study is to determine if the RT dose to SB affects the acute lower gastrointestinal toxicity (ALGIT) in rectal cancer patients who received neoadjuvant concurrent chemotherapy-IMRT. We will also evaluate if patient and tumor factors affect the ALGIT. METHODS: We retrospectively analyzed 63 rectal cancer patients that consecutively received preoperative IMRT (45 Gy for pelvis and 50 Gy for gross tumor in 25 fractions) with concurrent chemotherapy (oxaliplatin 130 mg/m(2) on day 1 and capecitabine 825 mg/m(2), twice per day from day 1 to day 14, week 1 and 4) between May 2012 and May 2013. The ALGIT was assessed with Common Terminology Criteria for Adverse Events version 3. The patients were stratified into two groups (with and without grade ≥2 ALGIT). The effect of SB volume receiving 5 to 40 Gy (V5 to V40) at a 5 Gy interval dose level on grade ≥2 ALGIT was evaluated. The volume of small bowel is defined as the volume of the small bowel loop. Other factors evaluated include patient's age and gender, tumor size and location and preexisting number of daily bowel movements. RESULTS: Overall, grade ≥2 ALGIT occurred in 57 % (36/63) patients. There was no significant difference between the two groups of patients (with and without grade ≥2 ALGIT) in SB V5 to V40, patient's age and gender, tumor location and preexisting number of daily bowel movements. There was a significant difference between the two groups of patients in tumor volume (with grade ≥2 ALGIT: 115.5 ± 85.5 cm(3) versus without grade ≥2 ALGIT: 58.5 ± 25.2 cm(3), p = 0.0001). Multivariate analysis revealed no association between the dose SB received (V5 to V40) and the grade ≥2 ALGIT after adjusting for the tumor volume. CONCLUSIONS: With IMRT technique used in rectal cancer patients undergoing preoperative chemo-radiotherapy, the acute lower GI toxicity is not associated with small bowel V5 to V40; instead it is associated with rectal tumor size.

Circadian gene expression predicts patient response to neoadjuvant chemoradiation therapy for rectal cancer.

Preoperative neoadjuvant chemoradiation therapy may be useful in patients with operable rectal cancer, but treatment responses are variable. We examined whether expression levels of circadian clock genes could be used as biomarkers to predict treatment response. We retrospectively analyzed clinical data from 250 patients with rectal cancer, treated with neoadjuvant chemoradiation therapy in a single institute between 2011 and 2013. Gene expression analysis (RT-PCR) was performed in tissue samples from 20 patients showing pathological complete regression (pCR) and 20 showing non-pCR. The genes analyzed included six core clock genes (Clock, Per1, Per2, Cry1, Cry2 and Bmal1) and three downstream target genes (Wee1, Chk2 and c-Myc). Patient responses were analyzed through contrast-enhanced pelvic MRI and endorectal ultrasound, and verified by histological assessment. pCR was defined histologically as an absence of tumor cells. Among the 250 included patients, 70.8% showed regression of tumor size, and 18% showed pCR. Clock, Cry2 and Per2 expressions were significantly higher in the pCR group than in the non-pCR group (P<0.05), whereas Per1, Cry1 and Bmal1 expressions did not differ significantly between groups. Among the downstream genes involved in cell cycle regulation, c-Myc showed significantly higher expression in the pCR group (P<0.05), whereas Wee1 and Chk2 expression did not differ significantly between groups. Circadian genes are potential biomarkers for predicting whether a patient with rectal cancer would benefit from neoadjuvant chemoradiation therapy.