ABSTRACT
Despite the complexity of allergic rhinitis (AR) pathogenesis, no FDA-approved drug has been developed to achieve optimal therapeutic effects. The present study explored the efficacy and mechanism of Huangqi (Hedysarum Multijugum Maxim)-Gancao (Glycyrrhizae Radix et Rhizoma or licorice) herb pair in treating AR by network pharmacology and experimental approaches. The bioactive ingredients of Huangqi and Gancao were identified and used to predict the targets of these herbs in AR and generate the pharmacological network. Ovalbumin (OVA)-induced AR mouse model was established to assess the anti-AR effect of the Huangqi decoction (HQD) prepared based on both herbs. We identified 90 active ingredients of the Huangqi-Gancao pair, targeting 69 AR-related genes. Quercetin (QUE) was identified as the hub ingredient of this pair, with 57 targets in AR. The protein-protein interaction (PPI) network analysis and molecular docking revealed IL1B, TNF, STAT1, IL6, PTGS2, RELA, IL2, NFKBIA, IFNG, IL10, IL1A, IRF1, EGFR, and CXCL10 as important targets of QUE in AR treatment. Experimentally, QUE or HQD significantly alleviated the AR-induced histopathological changes, AR symptoms, and IgE level and counteracted AR-induced expression changes of IFNG, IRF1, RELA, and NFKBIA. These effects were promoted by the NF-kB inhibitor helenalin, indicating that HQD and QUE counteracted AR in mice by regulating the IFNG/IRF1 signaling via the NF-κB pathway in AR mice. These findings shed light on the efficacy of the constituents of Huangqi-Gancao pair, their potential targets, and the molecular mechanisms of HQD in treating AR, which could advance the development of tailored therapeutic interventions for this disorder.
ABSTRACT
A photoacoustic (PA) imaging technique using the second near-infrared (NIR-II) window has attracted more and more attention because of its merits of deeper penetration depth and higher signal-to-noise (S/N) ratio than that using the first near-infrared (NIR-I) one. However, the design and development of high-performance PA imaging contrast agents in the NIR-II window is still a challenge. A semiconducting polymer, constructed by asymmetric units, exhibits regiorandom characteristics that effectively increase the distortion of the backbone. This increase in the degree of twist can regulate the twisted intramolecular charge transfer (TICT) effect, resulting in an enhancement of the PA signal. In this paper, an asymmetric structural acceptor strategy is developed to improve the PA signals of the resulting semiconducting polymer (PATQ-MP) in the NIR-II window with improved brightness, higher S/N ratio, and better photothermal conversion efficiency compared to polymers with the same main-chain structure containing a symmetric acceptor. DFT analysis showed that PATQ-MP containing an asymmetric acceptor monomer had a larger dihedral angle, which effectively improved the PA signal intensity by enhancing the TICT effect. The PEG-encapsulated PATQ-MP nanoparticles exhibit promising performance in the PA imaging of mouse tumors in vivo, demonstrating the clear identification of microvessels as small as 100 µm along with rapid metabolism within a span of 5 h. Therefore, this work provides a unique molecular design strategy for improving the signal intensity of PA imaging in the NIR-II window.
Subject(s)
Photoacoustic Techniques , Polymers , Semiconductors , Photoacoustic Techniques/methods , Animals , Mice , Polymers/chemistry , Quinoxalines/chemistry , Female , Humans , Thiadiazoles/chemistry , Infrared Rays , Mice, Nude , Mice, Inbred BALB C , Contrast Media/chemistryABSTRACT
Tendons are fibroblastic structures that link muscle and bone. There are two kinds of tendon injuries, including acute and chronic. Each form of injury or deterioration can result in significant pain and loss of tendon function. The recovery of tendon damage is a complex and time-consuming recovery process. Depending on the anatomical location of the tendon tissue, the clinical outcomes are not the same. The healing of the wound process is divided into three stages that overlap: inflammation, proliferation, and tissue remodeling. Furthermore, the curing tendon has a high re-tear rate. Faced with the challenges, tendon injury management is still a clinical issue that must be resolved as soon as possible. Several newer directions and breakthroughs in tendon recovery have emerged in recent years. This article describes tendon injury and summarizes recent advances in tendon recovery, along with stem cell therapy, gene therapy, Platelet-rich plasma remedy, growth factors, drug treatment, and tissue engineering. Despite the recent fast-growing research in tendon recovery treatment, still, none of them translated to the clinical setting. This review provides a detailed overview of tendon injuries and potential preclinical approaches for treating tendon injuries.
Subject(s)
Genetic Therapy , Tendon Injuries , Tissue Engineering , Wound Healing , Tendon Injuries/therapy , Tendon Injuries/physiopathology , Humans , Wound Healing/physiology , Animals , Tissue Engineering/methods , Genetic Therapy/methods , Platelet-Rich Plasma , Tendons , Stem Cell Transplantation/methods , Intercellular Signaling Peptides and Proteins/therapeutic use , Intercellular Signaling Peptides and Proteins/metabolismABSTRACT
Cellulolytic bacteria ferment dietary fiber into short-chain fatty acids, which play an important role in improving fiber utilization and maintaining intestinal health. Safe and effective cellulolytic bacteria are highly promising probiotic candidates. In this study, we isolated three strains of Bacillus cereus, which exhibited cellulolytic properties, from Kele pig feces. To assess the genetic basis of cellulose degradation by the isolates, whole-genome sequencing was used to detect functional genes associated with cellulose metabolism. Subsequently, we identified that the B. cereus CL2 strain was safe in mice by monitoring body weight changes, performing histopathologic evaluations, and determining routine blood indices. We next evaluated the biological characteristics of the CL2 strain in terms of its growth, tolerance, and antibiotic susceptibility, with a focus on its ability to produce short-chain fatty acids. Finally, the intestinal flora structure of the experimental animals was analyzed to assess the intestinal environment compatibility of the CL2 strain. In this study, we isolated a cellulolytic B. cereus CL2, which has multiple cellulolytic functional genes and favorable biological characteristics, from the feces of Kele pigs. Moreover, CL2 could produce a variety of short-chain fatty acids and does not significantly affect the diversity of the intestinal flora. In summary, the cellulolytic bacterium B. cereus CL2 is a promising strain for use as a commercial probiotic or in feed supplement. IMPORTANCE: Short-chain fatty acids are crucial constituents of the intestinal tract, playing an important and beneficial role in preserving the functional integrity of the intestinal barrier and modulating both immune responses and the structure of the intestinal flora. In the intestine, short-chain fatty acids are mainly produced by bacterial fermentation of cellulose. Therefore, we believe that safe and efficient cellulolytic bacteria have the potential to be novel probiotics. In this study, we systematically evaluated the safety and biological characteristics of the cellulolytic bacterium B. cereus CL2 and provide evidence for its use as a probiotic.
Subject(s)
Bacillus cereus , Probiotics , Animals , Swine , Mice , Bacillus cereus/genetics , Fatty Acids, Volatile , Intestines , CelluloseABSTRACT
RATIONALE: Acute fibrinous and organizing pneumonia (AFOP) is a rare acute or subacute interstitial lung disorder characterized by the deposition of fibrin within the alveoli and organizing pneumonia with a patchy distribution. The clinical features of AFOP are nonspecific, and it is often misdiagnosed as pneumonia, cancer, tuberculosis, or other lung disorders. PATIENT CONCERNS: In this case report, a 58-year-old woman presented with chest tightness, shortness of breath, cough and sputum. A chest CT scan showed multiple patchy shadows in both lungs. She was initially diagnosed with community-acquired pneumonia. Her purified protein derivative skin test was positive, but sputum was negative for acid-fast bacilli. DIAGNOSES: AFOP was diagnosed by bronchoscopic lung biopsy and histopathology. INTERVENTIONS: Following AFOP diagnosis, all anti-infective drugs were discontinued, and replaced by methylprednisolone and prednisone. OUTCOMES: After 1 week of treatment with methylprednisolone 40 mg daily, the patient chest CT and clinical symptoms improved. After 1 month, the patient symptoms had demonstrated dramatic improvement and CT scan revealed complete absorption of lesions in both lungs. After 5 months of follow-up, the patient symptoms completely disappeared. LESSONS: Acute AFOP is an uncommon lung condition with poor prognosis; hence, early diagnosis and identification are particularly important. Definitive diagnosis requires histopathological findings. Currently, there is no unified treatment guideline for AFOP, and treatment must be tailored based on the etiology and severity of each individual patient disease. Subacute AFOP shows a good response to corticosteroid treatment.
Subject(s)
Cryptogenic Organizing Pneumonia , Organizing Pneumonia , Pneumonia , Humans , Female , Middle Aged , Early Detection of Cancer , Pneumonia/drug therapy , Lung/diagnostic imaging , Lung/pathology , Methylprednisolone/therapeutic use , Cryptogenic Organizing Pneumonia/diagnosis , Cryptogenic Organizing Pneumonia/drug therapy , Cryptogenic Organizing Pneumonia/pathologyABSTRACT
Treatment of esophageal perforation or rupture is complicated and controversial, especially in advanced cases. In fact, it is generally accepted that this disease must be treated individually according to the location, causes and clinical features of rupture or perforation. A very rare case was admitted to our department, who was injured 5 days ago by high-pressure gas of a running air compressor and resulted in a long-term longitudinal rupture of the thoracic esophagus. Although the patient suffered from empyema and mediastinitis at the same time, and his condition was very serious, the debridement and desquamation of empyema were still implemented, followed by left thoracic esophagectomy and left neck approach esophagogastrostomy in the same period successfully. The patient got a good result finally.
Subject(s)
Empyema , Esophageal Perforation , Esophagoplasty , Mediastinitis , Humans , Mediastinitis/surgery , Esophageal Perforation/surgery , EsophagectomyABSTRACT
An emerging application of nanotechnology in medicine currently being developed involves employing nanoparticles to deliver drugs, heat, light, or other substances to specific types of cells (such as cancer cells). As most biological molecules exist and function at the nanoscale, engineering and manipulating matter at the molecular level has many advantages in the field of medicine (nanomedicine). Although encouraging, it remains unclear how much of this will ultimately result in improved patient care. In surgical specialties, clinically relevant nanotechnology applications include the creation of surgical instruments, suture materials, imaging, targeted drug therapy, visualization methods, and wound healing techniques. Burn lesion and scar management is an essential nanotechnology application. Prevention, diagnosis, and treatment of numerous orthopedic conditions are crucial technological aspects for patients' functional recovery. Orthopedic surgery is a specialty that deals with the diagnosis and treatment of musculoskeletal disorders. In recent years, the field of orthopedics has been revolutionized by the advent of nanotechnology. Using biomaterials comprised of nanoparticles and structures, it is possible to substantially enhance the efficacy of such interactions through nanoscale material modifications. This serves as the foundation for the majority of orthopedic nanotechnology applications. In orthopedic surgery, nanotechnology has been applied to improve surgical outcomes, enhance bone healing, and reduce complications associated with orthopedic procedures. This mini-review summarizes the present state of nanotechnology in orthopedic surgery, including its applications as well as possible future directions.
ABSTRACT
Previous evidences have shown that lncRNA AK001058 serves as an oncogene. This study aims to elucidate the expression characteristic of AK001058 in NSCLC samples, and its potential influence on the malignant progression and cisplatin resistance of NSCLC. Relative levels of AK001058 and IGF2 in NSCLC and non-tumoral tissues were detected by qRT-PCR. Proliferation inhibition rate and migratory rate in DDP-induced SPC-A1 and A549 cells were examined by CCK-8 and Transwell assay, respectively. Subsequently, DDP-resistant SPC-A1 and A549 cell lines were generated, and the role of AK001058 in affecting their cell phenotypes was determined. Using dual-luciferase reporter assay, the binding relationship between AK001058 and IGF2 was verified. Their co-regulation on DDP-resistant NSCLC cells was finally explored via rescue experiments. AK001058 was upregulated in NSCLC samples. The proliferative rate was dose-dependently and time-dependently declined in DDP-induced SPC-A1 and A549 cells. Cisplatin induction upregulated AK001058 in NSCLC cells, and attenuated migratory potential. Transfection of sh-AK001058 reduced proliferative and migratory rates in SPC-A1/DDP and A549/DDP cells. IGF2 was the downstream target binding AK001058, which was lowly expressed in NSCLC samples. AK001058 upregulation in NSCLC reduces cisplatin sensitivity and promotes malignant progression by negatively regulating IGF2, leading to cisplatin resistance.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , MicroRNAs , RNA, Long Noncoding , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/metabolism , Cisplatin/pharmacology , Cisplatin/therapeutic use , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , MicroRNAs/genetics , Drug Resistance, Neoplasm/genetics , Cell Line, Tumor , A549 Cells , Biomarkers , Cell ProliferationABSTRACT
This study demonstrates a new transformation path from lignin to graphene and nanodiamonds (NDs) by femtosecond laser writing in air at ambient temperature and pressure. Graphene nanoribbon rolls were generated at lower laser power. When the laser power was high, NDs could be obtained apart from graphene and onion-like carbon intermediates. These structures were confirmed by scanning electron microscopy, X-ray diffraction, Raman spectroscopy, X-ray photoelectron spectroscopy, and high-resolution transmission electron microscopy. The effects of laser power and laser writing speed on the structure of laser-induced patterns were investigated. The results show that the laser power was more important than the writing speed for the synthesis of carbon nanoparticles, and high laser power contributed to enhanced electrically conductive performance. Therefore, the direct laser irradiation technique leads a simple, low-cost, and sustainable way to synthesize graphene and NDs and is promising for the fabrication of sensors and electric devices.
ABSTRACT
To overcome the delignification saturation point in traditional alkaline hydrogen peroxide pretreatment (AHP), a powerful modified AHP delignification methodology was established by introducing ethanol into the system. The pretreatment caused significant lignin removal of bamboo at elevated pretreatment temperature with the highest lignin removal reaching 80.0% at 100 °C, higher than that (74.9% lignin removal) in pretreatment without the ethanol assistance. In addition, a certain amount of carbohydrates was also solubilized during the process whose recovery was 83.3% (glucan) and 67.6% (hemicellulose), respectively. The pretreated solid exhibited excellent enzymatic digestibility, with hydrolysis yields of ~100% and 95.7% for glucan and xylan, respectively. Our studies further indicate that this delignification methodology is versatile for hardwood and herbaceous plants, but does not perform well on softwood.
Subject(s)
Ethanol , Lignin , Glucans , Hydrogen Peroxide , HydrolysisABSTRACT
Wood is the main feedstock source for pulp and paper industry. However, chemical composition variations from multispecies and multisource feedstock heavily affect the production continuity and stability. As a rapid and non-destructive analysis technique, near infrared (NIR) spectroscopy provides an alternative for wood properties on-line analysis and feedstock quality control. Herein, near infrared spectroscopy coupled with partial least squares (PLS) regression was used to predict holocellulose and lignin contents of various wood species including poplars, eucalyptus and acacias. In order to obtain more accurate and robust prediction models, a comparison was conducted among several variable selection methods for NIR spectral variables optimization, including competitive adaptive reweighted sampling (CARS), Monte Carlo-uninformative variable elimination (MC-UVE), successive projections algorithm (SPA), and genetic algorithm (GA). The results indicated that CARS method displayed relatively higher efficiency over other methods in elimination of uninformative variables as well as enhancement of the predictive performance of models. CARS-PLS models showed significantly higher robustness and accuracy for each property using lowest variable numbers in cross validation and external validation, demonstrating its applicability and reliability for prediction of multispecies feedstock properties.
ABSTRACT
A combination process of alkali impregnation and refining was used as a pretreatment to improve the production of fermentable sugar. The surface structures and crystallinities of wood samples were characterized to explain the relationships between the pretreatment action and enzymatic efficiency. After refining, the reducing sugar contents in hydrolyzates were analyzed by UV-Vis and HPLC. The results showed that the enzymatic efficiency could be improved by the combined pretreatment, due to the increment of specific surface area and the release of more free hydroxyls. Comparing to the sodium hydroxide and deionized water, the impregnation with magnesium hydroxide had low refining energy consumption and high yield of reducing sugar (glucose and xylose) in enzymolysis process, where about 560 kWh/t of the energy was saved in refining, and the yield of the reducing sugar was as high as 91.53%. And the enzymolysis could be improved by a certain amount of magnesium ions.
Subject(s)
Alkalies/pharmacology , Biotechnology/methods , Cellulase/pharmacology , Eucalyptus/drug effects , Wood/drug effects , Carbohydrate Metabolism/drug effects , Crystallization , Fermentation/drug effects , Hydrolysis/drug effects , Ions , Magnesium/pharmacology , Surface Properties , ThermodynamicsABSTRACT
OBJECTIVE: To observe the changes in serum contents of interleukin-6 (IL-6) and interleukin-10 (IL-10) in patients with severe burn injury, and to investigate their relation with occurrence of sepsis and prognosis of patients. METHODS: One-hundred and sixty adult patients admitted into our hospital (1.0 ± 6.0) h after injury during March 2007 to March 2011 with massive and severe burns were enrolled in the investigation. Patients were divided into non-sepsis group (NS, n = 112), sepsis-survival group (SS, n = 36), and sepsis-deceased group (SD, n = 12) based on the occurrence of sepsis and death. Sepsis occurred on post burn day (PBD) 9 ± 5 in patients in the latter two groups. Patients died on PBD 18 ± 4 in SD group. Twenty healthy adult volunteers were chosen as healthy control group (HC). The age of subjects for observation among four groups, and total burn area and full-thickness burn area of patients among NS, SS, and SD groups were compared. Serum was isolated from blood samples collected from each patient every day from day of admission till PBD 20 to determine the contents of IL-6 and IL-10 by ELISA, and the same determinations were done in HC group. Data of trial subjects were processed with one-way analysis of variance. Data of IL-6 and IL-10 contents were processed with analysis of variance of repeated measure data and SNK method (q test). RESULTS: (1) There was no significant statistical difference among four groups in age (F = 2.090, P > 0.05). Total burn areas of patients in SS and SD groups were significantly larger than that in NS group (q test, with P values both below 0.05), and total burn area of patients in SD group was obviously larger than that in SS group (q test, P < 0.05). Full-thickness burn areas of patients in SS and SD groups were significantly larger than that in NS group (q test, with P values both below 0.05). (2) Serum contents of IL-6 of patients in NS, SS, and SD groups from PBD 1 to 20 were obviously higher than that of volunteers in HC group. There was no significant statistical difference among NS, SS, and SD groups in serum contents of IL-6 from PBD 1 to 7 (with F value from 0.188 to 2.897, P values all above 0.05). Serum content of IL-6 of patients in NS group decreased from PBD 4. Serum content of IL-6 of patients in SS group decreased gradually from PBD 13, but that in SD group increased continuously at the same time points. Serum contents of IL-6 of patients in NS group [(262 ± 25) pg/mL on PBD 8] were lower than those in SS group [(287 ± 38) pg/mL on PBD 8, q test, P < 0.05] and SD group [(299 ± 22) pg/mL on PBD 8, q test, P < 0.05] from PBD 8. Serum contents of IL-6 of patients in SS group [(300 ± 33) pg/mL on PBD 13] were obviously lower than those in SD group [(338 ± 22) pg/mL on PBD 13, q test, P < 0.05] from PBD 13. (3) Serum contents of IL-10 of patients in NS, SS, and SD groups were higher than that in HC group at each time point. There was no significant statistical difference among NS, SS, and SD groups in serum contents of IL-6 from PBD 1 to 5 (with F values from 1.802 to 2.538, P values all above 0.05). Serum content of IL-10 of patients in NS group was obviously lower than that of patients in SD group from PBD 6 (q test, P values all below 0.05). On PBD 8, serum content of IL-10 of patients in SS group [(54 ± 19) pg/mL] was obviously lower than that in SD group [(91 ± 23) pg/mL, q test, P < 0.05]. The sum of sensitivity (83.33%, 10/12) and specificity (91.67%, 33/36) minus 1 was maximum when the critical value of IL-10 content was set at 77 pg/mL based on the comparison between SS group and SD group in serum content of IL-10 on PBD 8. CONCLUSIONS: The occurrence and outcome of sepsis is related to burn area and depth when the patients are in similar age. Serum contents of IL-6 and IL-10 play important roles in the pathogenesis of sepsis after burn. IL-6 content in early stage shall not be used in predicting the prognosis of patients with sepsis. IL-10 continuously higher than 77 pg/mL in early stage forecasts unfavorable prognosis of patient.
Subject(s)
Burns/blood , Burns/diagnosis , Interleukin-10/blood , Interleukin-6/blood , Sepsis/diagnosis , Adult , Burns/complications , Case-Control Studies , Female , Humans , Male , Prognosis , Sepsis/etiology , Serum/metabolism , Young AdultABSTRACT
OBJECTIVE: To investigate the therapic choice of intertrochanteric fractures of femur in aged patient. METHODS: From June 2006 to June 2010,58 patients with intertrochanteric fracture were treated with surgical methods. There were 25 males and 33 females, aged from 65 to 93 years old (averaged 79 years old). According to the Evans type, type I was in 30 cases, type II was in 28 cases. Of them, 25 patients were treated with hip replacement (group A) and 33 patients were treated with internal fixation (group B). The operative time, blood loss volume, the time of get out of bed, drainage volume, complications and function of joint motion were compared between two groups. According to Harris scoring to evaluate function of joint motion at the 3rd, 6th, 12th months after operation. RESULTS: All patients were followed up more than 12 months (averaged 16.4 months). One patient in group A died of pneumonia one month later after operation and other patients live safely through peri-operation. The group B was better than that of group A at operative time, blood loss volume, drainage volume. In group A, 1 case died and 1 case got DVT, 2 cases got urinary tract infection and 1 case got pneumonia. While in group B, 1 case got bedsore, 1 case got coxa vara and 2 cases got urinary tract infection. The incidence rate of complication in group B was lower than that of group A (P < 0.05). According to Harris scoring system, at the 3rd, 6th,12th months after operation, Harris scoring in group A was respectively (78.43 +/- 5.32), (81.67 +/- 4.87), (87.66 +/- 4.01) scores and in group B was respectively (75.45 +/- 3.22), (76.33 +/- 4.12), (88.65 +/- 3.77) scores. There was statistical significance in Harris scoring at the 3rd, 6th months after operation between two groups (P < 0.05) and there was no statistical significance at the 12th months after operation (P > 0.05). At three months after operation, in group A,14 cases obtained excellent results, 5 good, 5 fair and 1 poor; and in group B, 8 cases obtained excellent results, 13 good, 9 fair and 3 poor. Six months later, in group A,18 excellent, 5 good, 2 fair and 0 poor, and in group B,10 excellent, 15 good, 6 fair and 2 poor. Twelve months later,in group A,18 excellent, 5 good, 1 fair and 1 poor; and in group B, 21 excellent, 9 good, 3 fair and 0 poor. Three and six months later after operation, the clinical effect in group A was better than that of group B (P < 0.05); but twelve months later, there was no significant differences between two groups (P > 0.05). CONCLUSION: The internal fixation is especially the preferred method for the aged patient with intertrochanteric fractures. Hip replacement refer to pathologicalfracture caused by cancer, unheeded fracture abnormity, osteoprosis too serious to be treated by internal fixation or patients with ipsilateral symptomatic degenerative joint or revisions caused by failed internal fixation and severely intertrochanteric comminuted fractures and merged severely osteoporosis.
Subject(s)
Hip Fractures/surgery , Aged , Aged, 80 and over , Arthroplasty, Replacement, Hip , Female , Fracture Fixation, Internal , Humans , Male , Postoperative Complications/epidemiology , Postoperative Complications/prevention & controlABSTRACT
OBJECTIVE: To study the effect and function of P16 protein during the development of lung cancer, in order to explore the differences of expression of P16 protein in non-small cell lung cancer (NSCLC) between Xuanwei and Kunming district. METHODS: 45 patients with NSCLC from Xuanwei and 45 patients from Kunming,18 patients from pneumatocele who underwent radical resection were collected. Immunohistochemical staining were used to analyze the expressions of P16 protein in paraffin-embedded tissues from these 90 residing patients with lung cancer. RESULTS: 45 cases with lung cancer were negative for P16 protein expression, total loss expression rates were 41.7% (45/108). Loss expression rates of Xuanwei,Kunming and pneumatocele were 57.8% (26/45), 37.8% (17/45), 11.1% (2/18), respectively. In comparition the loss expression of P16 protein in clinicopathologic characteristics between the two groups, there were some statistically significant differences in the loss expression rate of P16 (P < 0.05): the loss expression rate of P16 in cases with stage I, adenocarcinoma and stage T2 in Xuanwei were more higher than those in Kunming; the loss expression rates of P16 in Xuanwei and Kungming were more higher than those in pneumatocele respectively. CONCLUSION: Loss expression rates of P16 protein in the early stage and adenocarcinoma in Xuanwei lung cancer group were significant difference compared with in Kunming lung cancer group.
Subject(s)
Carcinoma, Non-Small-Cell Lung/metabolism , Cyclin-Dependent Kinase Inhibitor p16/metabolism , Lung Neoplasms/metabolism , Adult , Aged , China , Female , Humans , Immunohistochemistry/methods , Male , Middle AgedABSTRACT
BACKGROUND AND OBJECTIVE: Our previous studies have shown that dendritic cell (DC)-tumor cell fusion vaccine can induce specific antitumor response against esophageal carcinoma cells. This study was to investigate the inhibitory effect of intratumor injection of the antigen-specific cytotoxic T lymphocytes (CTLs) induced by DC-tumor cell fusion vaccine against subcutaneously transplanted esophageal carcinoma cells in nude mice, and to analyze the influence of DC/tumor cell fusion vaccine on proliferation and apoptosis of esophageal carcinoma cells. METHODS: Fusion cell vaccine of mature DCs with EC109 cells were generated by the polyethylene glycol (PEG) protocol and the antigen-specific CTLs were induced. The models of transplanted human esophageal carcinoma in nude mouse were established using EC-109 cell line. Thirty-three nude mice with subcutaneous tumors were randomly divided into three groups. Subcutaneous tumors of group A (n=11), group B (n=11) and group C (n=11) were intratumorally injected with the CTLs induced by DC/tumor fusion vaccine, T lymphocytes and RPMI 1,640 medium respectively once a week. After four weeks of intratumor injection, the nude mice were killed and the nodules were anatomized. The mean volume and weight of tumors of each group were measured, and the tumor inhibitory rates of the Group A and the Group B were calculated and compared. The expression of proliferating cell nuclear antigen (PCNA) was detected by immunohistochemistry (S-P method). The mean PCNA-label index (LI) of three groups was compared. The cell cycle and cell apoptosis of the xenograft tumor cells were analyzed by flow cytometry. The mean S-phase fraction (SPF) and the mean rate of cell apoptosis of three groups was compared respectively. RESULTS: Both the mean volume and the mean weight of xenograft tumors in group A (881.45+/-31.14 mm3 and 0.88+/-0.04 g) were significantly smaller than those of group B (1493.37+/-51.67 mm3 and 1.38+/-0.07 g) and group C (2065.77+/-87.55 mm3 and 2.04+/-0.11 g). The tumor inhibitory rates of Group A was significantly higher than that of group B (56.86% vs. 32.35%, F=1218.08, P=0.001). The mean PCNA-LI of xenograft tumors was less in the group A (26.83+/-0.95)% than in the group B (51.82+/-1.51)% and group C (68.93+/-2.40)% (F=1528.39, P=0.000). The mean SPF of xenograft tumors was less in the group A (12.46+/-0.36)% than in the group B (29.39+/-0.96)% and the group C (42.25+/-1.43)% (P<0.05). The mean apoptotic rate of xenograft tumors was less in the group A (38.03+/-1.21)% than in the group B (17.75+/-0.56)% and the group C (6.59+/-0.22)% (P<0.05). CONCLUSION: The model of subcutaneous xenograft tumors in nude mice using human esophageal carcinoma cell line EC-109 has been successfully established. CTLs induced by DC/tumor fusion vaccine has specific antitumor immunity efficacy in vivo. CTLs can inhibit the proliferation of tumor cells and induce apoptosis of tumor cells in local tumors.
Subject(s)
Cancer Vaccines/immunology , Dendritic Cells/immunology , Esophageal Neoplasms/pathology , Proliferating Cell Nuclear Antigen/metabolism , T-Lymphocytes, Cytotoxic/immunology , Animals , Apoptosis , Cell Cycle , Cell Fusion , Cell Line, Tumor , Cell Proliferation , Dendritic Cells/cytology , Esophageal Neoplasms/immunology , Esophageal Neoplasms/metabolism , Humans , Male , Mice , Mice, Inbred BALB C , Mice, Nude , Neoplasm Transplantation , Random Allocation , Tumor BurdenABSTRACT
BACKGROUND & OBJECTIVE: Unexpected splenectomy is sometimes performed simultaneously with radical esophagectomy for esophageal carcinoma because of spleen injury or anatomical abnormity. This study was to investigate the influence of unexpected simultaneous splenectomy on postoperative complications and prognosis of patients undergoing radical esophagectomy for esophageal carcinoma. METHODS: Clinical data of 843 esophageal carcinoma patients, underwent esophagectomy (R0 resection) at Cancer Center of Sun Yat-sen University from Aug. 1999 to Jul. 2002, were analyzed. Of these patients, 39 (4.6%) underwent splenectomy. The clinicopathologic parameters and prognosis of the patients in splenectomy group and non-splenectomy group were compared. RESULTS: The amount of intraoperative blood loss was significantly higher in splenectomy group than in non-splenectomy group [(380+/-113) ml vs. (305+/-85) ml, P<0.001]. However, there were no significant differences in clinicopathologic characteristics, intraoperative or postoperative complications between the 2 groups (P>0.05). The occurrence rate of pulmonary complications was higher in splenectomy group than in non-splenectomy group (17.9% vs. 8.5%, P>0.05). The median survival time was shorter in splenectomy group than in non-splenectomy group (18.4 months vs. 21 months, P>0.05). CONCLUSION: Unexpected simultaneous splenectomy had no effect on the long-term survival of patients who underwent radical esophagectomy for esophageal carcinoma, but it may result in more intraoperative blood loss and pulmonary complications.
Subject(s)
Carcinoma, Squamous Cell/surgery , Esophageal Neoplasms/surgery , Esophagectomy/methods , Medical Errors , Postoperative Complications , Splenectomy , Adult , Aged , Blood Loss, Surgical , Esophagectomy/adverse effects , Female , Humans , Intraoperative Complications , Male , Medical Errors/adverse effects , Middle Aged , Neoplasm Staging , Pneumonia/etiology , Splenectomy/adverse effects , Survival RateABSTRACT
BACKGROUND & OBJECTIVE: Mucin-1 (MUC1), a tumor-associated antigen, is an optional molecular target for antitumor immunotherapy protocols. This study was to establish a subcutaneous human esophageal cancer transplantation model with MUC1 high expression in nude mice that closely resembles the biological features of human esophageal cancer, and provide a in vivo model for MUC1-targeting immunotherapy of esophageal cancer. METHODS: Human esophageal carcinoma cell line EC-109 with MUC1 high expression was cultured, and subcutaneously transplanted into BALB/c athymic nude mice (4-5 weeks old). The growth status of transplanted tumor was observed. These subcutaneous tumors were examined histologically. The expression of proliferating cell nuclear antigen (PCNA) was detected by immunohistochemistry. Cell cycle and MUC1 expression of the transplanted tumor cells were analyzed by flow cytometry. RESULTS: Human esophageal carcinoma transplantation models with MUC1 high expression were successfully established in 6 of the 7 nude mice. The histological and biological characteristics of subcutaneous transplanted tumors were similar to those of human esophageal carcinoma. The mean PCNA label index of subcutaneous transplanted tumor cells was (63.5+/-3.6)%. The mean S-phase fraction of cell cycle was (37.6+/-3.7)%. The positive rate of MUC1 in subcutaneous transplanted tumor cells was 97.5%. CONCLUSION: Human esophageal carcinoma transplantation model with MUC1 high expression in nude mice is similar to human malignant tumors in biological characteristics, and can be used to investigate the biological characteristics of esophageal carcinoma, as well as provides an applicable animal model for research on MUC1-targeting immunotherapy of esophageal cancer.
Subject(s)
Disease Models, Animal , Esophageal Neoplasms/immunology , Mucin-1/metabolism , Animals , Cell Cycle , Cell Line, Tumor , Esophageal Neoplasms/pathology , Flow Cytometry , Humans , Immunohistochemistry , Male , Mice , Mice, Inbred BALB C , Mice, Nude , Neoplasm Transplantation , Proliferating Cell Nuclear Antigen/metabolismABSTRACT
BACKGROUND & OBJECTIVE: Dendritic cells (DCs) are antigen-presenting cells, and DC-based fusion vaccine of DCs with tumor cells can induce specific immune response against tumor cells effectively. This study was to investigate the antitumor immunity efficacy of fusion vaccine of DCs with human esophageal carcinoma EC109 cells in vitro. METHODS: Peripheral blood mononuclear cells (PBMCs) from healthy volunteers were isolated, and cultured with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) and interleukin-4 (IL-4) to generate DCs. Fusion cells of DCs with EC109 cells were generated by polyethylene glycol (PEG) protocol. The T-cell proliferation response stimulated by DC/EC109 cells was detected by MTT assay. The killing efficacy of cytotoxic T lymphocytes (CTLs), activated by DC/EC109 cells, on EC109 cells was evaluated by LDH assay in vitro, and compared with the killing efficacy on human gastric carcinoma SGC7901 cells and human breast cancer MCF7 cells. RESULTS: The highest fusion efficiency of DCs with EC109 cells was 22.25%. The stimulating efficacy of DC/EC109 cells on the proliferation of T cells was significantly higher than those of DCs and EC109 cells (P<0.05). DC/EC109 cells induced specific CTLs against EC109 cells, and the killing efficacy of the CTLs was significantly higher for EC109 cells than for SGC7901 cells or MCF7 cells (P<0.05). CONCLUSION: C/EC109 fusion vaccine can induce specific antitumor response against EC109 cells effectively.