The physical and cellular mechanism of structural color change in zebrafish.

Many animals exhibit remarkable colors that are produced by the constructive interference of light reflected from arrays of intracellular guanine crystals. These animals can fine-tune their crystal-based structural colors to communicate with each other, regulate body temperature, and create camouflage. While it is known that these changes in color are caused by changes in the angle of the crystal arrays relative to incident light, the cellular machinery that drives color change is not understood. Here, using a combination of 3D focused ion beam scanning electron microscopy (FIB-SEM), micro-focused X-ray diffraction, superresolution fluorescence light microscopy, and pharmacological perturbations, we characterized the dynamics and 3D cellular reorganization of crystal arrays within zebrafish iridophores during norepinephrine (NE)-induced color change. We found that color change results from a coordinated 20° tilting of the intracellular crystals, which alters both crystal packing and the angle at which impinging light hits the crystals. Importantly, addition of the dynein inhibitor dynapyrazole-a completely blocked this NE-induced red shift by hindering crystal dynamics upon NE addition. FIB-SEM and microtubule organizing center (MTOC) mapping showed that microtubules arise from two MTOCs located near the poles of the iridophore and run parallel to, and in between, individual crystals. This suggests that dynein drives crystal angle change in response to NE by binding to the limiting membrane surrounding individual crystals and walking toward microtubule minus ends. Finally, we found that intracellular cAMP regulates the color change process. Together, our results provide mechanistic insight into the cellular machinery that drives structural color change.

Cancer associated fibroblast derived gene signature determines cancer subtypes and prognostic model construction in head and neck squamous cell carcinomas.

BACKGROUND: Head and neck squamous cell carcinomas (HNSCC) are the most common type of head and neck cancer with an unimproved prognosis over the past decades. Although the role of cancer-associated-fibroblast (CAF) has been demonstrated in HNSCC, the correlation between CAF-derived gene expression and patient prognosis remains unknown. METHODS: A total of 528 patients from TCGA database and 270 patients from GSE65858 database were contained in this study. After extracting 66 CAF-related gene expression data from TCGA database, consensus clustering was performed to identify different HNSCC subtypes. Limma package was used to distinguish the differentially expression genes (DEGs) between these subtypes, followed by Lasso regression analysis to construct a prognostic model. The model was validated by performing Kaplan-Meier survival, ROC and risk curve, univariate and multivariate COX regression analysis. GO, KEGG, GSEA, ESTIMATE and ssGSEA analyses was performed to explort the potential mechanism leading to different prognosis. RESULTS: Based on the 66 CAF-related gene expression pattern we stratitied HNSCC patients into two previously unreported subtypes with different clinical outcomes. A prognostic model composed of 15 DEGs was constructed and validated. In addition, bioinformatics analysis showed that the prognostic risk of HNSCC patients was also negatively correlated to immune infiltration, implying the role of tumor immune escape in HNSCC prognosis and treatment option. CONCLUSIONS: The study develops a reliable prognostic prediction tool and provides a theoretical treatment guidance for HNSCC patients.

Basic research of the relationship between irradiation dose and volume in radiation-induced pulmonary injury / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Irradiation dose and volume are the major physical factors of radiation-induced lung injury. The study investigated the relationships between the irradiation dose and volume in radiation-induced lung injury by setting up a model of graded volume irradiation of the rat lung.</p><p><b>METHODS</b>Animals were randomly assigned to three groups. The ELEKTA precise 2.03 treatment plan system was applied to calculate the irradiation dose and volume. The treatment plan for the three groups was: group 1 received a "high dose to a small volume" (25% volume group) with the mean irradiation volume being 1.748 cm(3) (25% lung volume); the total dose and mean lung dose (MLD) were 4610 cGy and 2006 cGy, respectively (bilateral AP-PA fields, source to axis distance (SAD) = 100 cm, 6MVX, single irradiation); Group 2 received a "low dose to a large volume" (100% volume group) with the mean irradiation volume being 6.99 cm(3) (100% lung volume); the total dose was 1153 cGy. MLD was 2006 cGy, which was the same as that of group 1 (bilateral AP-PA fields, SAD = 100 cm, 6MVX, single irradiation); Group 3 was a control group. With the exception of receiving no irradiation, group 3 had rest steps that were the same as those of the experimental groups. After irradiation, functional, histopathological, and CT changes were compared every two weeks till the 16th week.</p><p><b>RESULTS</b>Functionally, after irradiation breath rate (BR) increases were observed in both group 1 and group 2, especially during the period of 6th - 8th weeks. The changes of BR in the 100% volume group were earlier and faster. For the 25% volume group, although pathology was more severe, hardly any obvious increase in BR was observed. Radiographic changes were observed during the early period (the 4th week) and the most obvious changes manifested during the mediated period (the 8th week). The extensiveness of high density and the decreased lung permeability were presented in the 100% volume group, and ground glass opacity and patchy consolidation were presented in the 25% volume group without pleural effusion, pleural thickening, and lung shrinking. Morphologically, the 100% volume group mainly presented signs of vascular damage, including signs of vascular wall edemas, hypertrophy, and sclerosis. The 25% volume group mainly presented with erythrocyte cell exudation, inflammation, and parenchymal damage.</p><p><b>CONCLUSIONS</b>The delivery of a small dose of radiation to a large volume is not safe. A low dose smeared out over large volumes, albeit reversible, may lead to fatal respiratory dysfunction. Damage to the lung may be more dependent on the volume of irradiation than on the radiation dose. Clinically, the safest approach is to limit both the volume of the irradiated normal lung and the amount of received radiation.</p>

Weekly paclitaxel and carboplatin with concurrent three dimensional conformal radiotherapy for locally advanced non small cell lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the toxicity and efficacy of weekly chemotherapy of paclitaxel and carboplatin with concurrent three dimensional conformal radiotherapy (3D-CRT)for locally advanced non small cell lung cancer(NSCLC).</p><p><b>METHODS</b>From July 2002 to July 2004, a non-randomized prospective study of 52 patients with locally advanced NSCLC treated with 3D-CRT and chemotherapy by paclitaxel and carboplatin were carried out. Of the 52 patients, 21 received concurrent chemoradiation with 3D-CRT and weekly paclitaxel and carboplatin (concurrent chemoradiation group), 31 received sequential chemoradiation with paclitaxel and carboplatin and 3D-CRT (sequential chemoradiation group). In the concurrent chemoradiation group, paclitaxel 40 mg/m2 was administered intravenously for 1 hour. Carboplatin of 1.5 AUC/cycle was used after administration of paclitaxel on D1, D8, D15, D29, D36 and D143. In the sequential chemoradiation group, two cycles of chemotherapy were given at two weeks before radiotherapy. Paclitaxel 150 mg/m2 and carboplatin 5 AUC/cycle were administered on D1 and D21. 3D-CRT was given at two weeks after the second cycle of chemotherapy provided that the hematological examination was normal. 3D-CRT was given at 1.8-2.0 Gy/f to a total dose of 60-66 Gy/6-8 weeks.</p><p><b>RESULTS</b>All the patients completed the trial, but 12 had prolongation of treatment time for more than 1 week due to severe leucopenia with 5 in concurrent chemoradiation group and 7 in sequential chemoradiation group. The rate of complete response (CR), partial response (PR), progress of disease (NC + PD) and overall response was 9.5% (2/21), 71.4% (15/21), 19.0% (4/21) and 81.0%, respectively, in concurrent group, versus 6.5% (2/31), 67.7% (21/31), 25.8% (8/31) and 74.2% in sequential group (CR), respectively. II-III grade of esophagitis, pneumonia and leukocytopenia observed in concurrent chemoradiation group was 61.9% (13/21), 41.9% (13/31) and 23.8% (5/21) ,versus 22.6% (7/31), 42.9 % (9/21) and 19.4% (6/31), respectively, in the sequential chemoradiation group. One of those patients in concurrent chemoradiation group had IV grade of leukocytopenia. The overall median survival time was 17.5 months with 19.0 months for concurrent chemoradiation group, 15.8 months for sequential chemoradiation group. The Overall 1-, 2-year survival rate was 72.0%, 37.0%, respectively and 1 - and 2 - year local control rate was 75.0% and 75.0%.</p><p><b>CONCLUSION</b>Our data indicate that concurrent chemoradiotherapy is safe and effective for locally advanced non small cell lung cancer. Concurrent chemoradiotherapy may be helpful in improving response and survival than sequential one, but no significant difference is observed between two groups in this series(P > 0.05). Further randomized prospective study is still needed to prove it.</p>

Treatment and prognosis of 135 nasal non-Hodgkin′s lymphoma patients / 中华放射肿瘤学杂志

Objective To evaluate the effects of nasal non-Hodgkin′s lymphoma(N-NHL) treated with chemotherapy alone, radiotherapy alone, chemotherapy plus radiotherapy and autologous peripheral blood stem cell transplantation(APBSCT) combined with total body irradiation(TBI);and to analyze the impact factors of prognosis. Methods 135 patients were treated between 1980 and 2000. All were confirmed by histopathology as N-NHL, including 122 T cell in origin, 12 B cell and 1 NK cell in origin. The main radiotherapy portal was set in front of the nose with a spade-like protrusion, supplement with a portal next to the ear on one side or both sides. Combined portal in facial cervical area was first used when there was invasion of the oropharynx. The median dose to the nasal cavity was 56.0Gy with a range of 35.2 to 75.5Gy, with added 30Gy to the primary lesion in two patients. Six patients received TBI combined with APBSCT, with 8Gy in the TBI group. Chemotherapy, given before or during after radiotherapy or alone, consisted of 2-6 cycles of COP, COPP, COMP, CHOP or COBDP. Prognostic factors were analyzed with Cox model. Results The local control rate was 12%,69%,76% and 83% in chemotherapy alone, radiotherapy alone, chemotherapy plus radiotherapy and APBSCT combined with TBI, respectively(P=0.057).The 5-year survival rate was 9%,52%,63% and 83%,respectively(P=0.032). Multi-factor analysis showed that tumor extension and treatment methods were the most important prognostic factors besides Ann-Arbor stage, but gender, pathology, age and symptoms had little effect on prognosis .Conclusions Chemotherapy plus radiotherapy group achieves a better survival rate than radiotherapy alone. It is helpful to evaluate prognosis to make more detail subareas on basis of local extensions in Ann Arbor staging system.For some N-NHL patients with good financial condition, APBSCT combined with TBI is a good choice.