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1.
Radiat Oncol ; 14(1): 38, 2019 Mar 05.
Article in English | MEDLINE | ID: mdl-30836970

ABSTRACT

BACKGROUND: To explore the differences and correlations between the target volumes defined using preoperative prone diagnostic magnetic resonance imaging (MRI) and postoperative prone computed tomography (CT) simulation imaging based on deformable image registration (DIR) for external-beam partial breast irradiation (EB-PBI) after breast-conserving surgery (BCS). METHODS: Eighteen breast cancer patients suitable for EB-PBI were enrolled. Preoperative prone diagnostic MRI and postoperative prone CT scan sets for all the patients were acquired during free breathing. Target volumes and ipsilateral breast were all contoured by the same radiation oncologist. The gross tumor volume (GTV) delineated on the preoperative MRI images was denoted as the GTVpreMR and the tumor bed (TB) delineated on the postoperative prone CT images was denoted as the GTVpostCT. The MIM software system was used to deformably register the MRI and CT images. RESULTS: When based on the coincidence of the compared target centers, there were statistically significant increases in the conformity index (CI) and degree of inclusion (DI) values for GTVpostCT-GTVpreMR, GTVpostCT-CTVpreMR + 10, CTVpostCT + 10-GTVpreMR, and CTVpostCT + 10-CTVpreMR + 10 when compared with those based on the DIR of the thorax (Z = - 3.724, - 3.724, - 2.591, - 3.593, all P < 0.05; Z = -3.724, - 3.724, - 3.201, - 3.724, all P < 0.05, respectively). CONCLUSIONS: Although based on DIR, there was relatively poor spatial overlap between the preoperative prone diagnostic MRI images and the postoperative prone CT simulation images for either the whole breast or the target volumes. Therefore, it is unreasonable to use preoperative prone diagnostic MRI images to guide postoperative target delineation for EB-PBI.


Subject(s)
Breast Neoplasms/radiotherapy , Magnetic Resonance Imaging/methods , Radiographic Image Interpretation, Computer-Assisted/methods , Radiotherapy Planning, Computer-Assisted/methods , Tomography, X-Ray Computed/methods , Adult , Aged , Breast Neoplasms/surgery , Female , Humans , Mastectomy, Segmental , Middle Aged , Postoperative Period
2.
Radiat Oncol ; 13(1): 181, 2018 Sep 18.
Article in English | MEDLINE | ID: mdl-30227865

ABSTRACT

BACKGROUND: Concurrent chemoradiotherapy is considered curative intent treatment for patients with non-operative esophageal cancer. Radiation-induced heart damage receives much attention. We performed repeated four-dimensional computed tomography (4DCT) to detect changes in cardiac volume during radiotherapy for esophageal cancer patients, and explored potential factors responsible for those changes. METHODS: Forty-six patients with esophageal cancer underwent enhanced 4DCT and three-dimensional (3D) CT scans before radiotherapy and every 10 fractions during treatment. The heart was contoured on 3DCT images, 4DCT end expiratory (EE) images and 4DCT maximum intensity projection (MIP) images by the same radiation oncologist. Heart volumes and other relative parameters were compared by the SPSS software package, version 19.0. RESULTS: Compared with its initial value, heart volume was smaller at the 10th fraction (reduction = 3.27%, 4.45% and 4.52% on 3DCT, EE and MIP images, respectively, p < 0.05) and the 20th fraction (reduction = 6.05%, 5.64% and 4.51% on 3DCT, EE and MIP images, respectively, p < 0.05), but not at the 30th fraction. Systolic and diastolic blood pressures were reduced (by 16.95 ± 16.69 mmHg and 7.14 ± 11.64 mmHg, respectively, both p < 0.05) and the heart rate was elevated by 5.27 ± 6.25 beats/min (p < 0.05) after radiotherapy. None of the potential explanatory variables correlated with heart volume changes. CONCLUSIONS: Cardiac volume reduced significantly from an early treatment stage and maintained the reduction until the middle stage. The heart volume changes observed on 3DCT and 4DCT were consistent during radiotherapy. The changes in heart volume, blood pressure and heart rate may be valuable indicators of cardiac impairment and target dose changes.


Subject(s)
Carcinoma, Squamous Cell/therapy , Cardiac Volume/radiation effects , Chemoradiotherapy , Esophageal Neoplasms/therapy , Four-Dimensional Computed Tomography , Heart/diagnostic imaging , Heart/radiation effects , Aged , Female , Humans , Male , Prospective Studies , Radiotherapy Planning, Computer-Assisted
3.
Clin Cancer Res ; 23(8): 2038-2049, 2017 04 15.
Article in English | MEDLINE | ID: mdl-27683179

ABSTRACT

Purpose: Antiproliferative, antiviral, and immunomodulatory activities of endogenous type I IFNs (IFN1) prompt the design of recombinant IFN1 for therapeutic purposes. However, most of the designed IFNs exhibited suboptimal therapeutic efficacies against solid tumors. Here, we report evaluation of the in vitro and in vivo antitumorigenic activities of a novel recombinant IFN termed sIFN-I.Experimental Design: We compared primary and tertiary structures of sIFN-I with its parental human IFNα-2b, as well as affinities of these ligands for IFN1 receptor chains and pharmacokinetics. These IFN1 species were also compared for their ability to induce JAK-STAT signaling and expression of the IFN1-stimulated genes and to elicit antitumorigenic effects. Effects of sIFN-I on tumor angiogenesis and immune infiltration were also tested in transplanted and genetically engineered immunocompetent mouse models.Results: sIFN-I displayed greater affinity for IFNAR1 (over IFNAR2) chain of the IFN1 receptor and elicited a greater extent of IFN1 signaling and expression of IFN-inducible genes in human cells. Unlike IFNα-2b, sIFN-I induced JAK-STAT signaling in mouse cells and exhibited an extended half-life in mice. Treatment with sIFN-I inhibited intratumoral angiogenesis, increased CD8+ T-cell infiltration, and robustly suppressed growth of transplantable and genetically engineered tumors in immunodeficient and immunocompetent mice.Conclusions: These findings define sIFN-I as a novel recombinant IFN1 with potent preclinical antitumorigenic effects against solid tumor, thereby prompting the assessment of sIFN-I clinical efficacy in humans. Clin Cancer Res; 23(8); 2038-49. ©2016 AACR.


Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Interferon-alpha/chemistry , Interferon-alpha/pharmacology , Animals , Female , Flow Cytometry , Humans , Immunoblotting , Interferon alpha-2 , Mice , Mice, Inbred C57BL , Mice, Nude , Neoplasms, Experimental/drug therapy , Recombinant Proteins/chemistry , Recombinant Proteins/pharmacology , Surface Plasmon Resonance , Xenograft Model Antitumor Assays
4.
Asian Pac J Cancer Prev ; 17(5): 2573-7, 2016.
Article in English | MEDLINE | ID: mdl-27268632

ABSTRACT

OBJECTIVE: The aim of this study was to determine a method of dose prescription that minimizes normal tissue irradiation outside the planning target volume (PTV) during stereotactic body radiotherapy (SBRT) for patients with non-small cell lung cancer. METHODS: Previous research and patients with typical T1 lung tumors with peripheral lesions in the lung were selected for analysis. A PTV and several organs at risk (OARs) were constructed for the dose calculated; six treatment plans employing intensity modulated radiotherapy (IMRT) were produced, in which the dose was prescribed to encompass the PTV, with the prescription isodose level (PIL) set at 50, 60, 70, 80, 90 or 95% of the isocenter dose. Additionally, four OARs around the PTV were constructed to evaluate the dose received in adjacent tissues. RESULTS: The use of higher PILs for SBRT resulted in improved sparing of OARs, with the exception of the volume of lung treated with a lower dose. CONCLUSIONS: The use of lower PILs is likely to create significant inhomogeneity of the dose delivered to the target, which may be beneficial for the control of tumors with poor conformity indices.


Subject(s)
Carcinoma, Non-Small-Cell Lung/surgery , Lung Neoplasms/surgery , Organs at Risk/radiation effects , Radiosurgery/standards , Radiotherapy Planning, Computer-Assisted/standards , Radiotherapy, Intensity-Modulated/standards , Algorithms , Humans , Radiosurgery/methods , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted/methods , Radiotherapy, Intensity-Modulated/methods
5.
Int J Clin Exp Pathol ; 7(9): 6395-8, 2014.
Article in English | MEDLINE | ID: mdl-25337298

ABSTRACT

Mixed adenoneuroendocrine carcinoma (MANEC) is exceedingly rare with a poor outcome. In this article, we reported a MANEC in a 68-year-old woman with a symptom of abdominal pain and distension. MANEC derived from the ascending colon with highly aggressive behavior. The diagnosis and distinguish of MANEC must base on histological findings and immunohistochemical findings. In this case, microscopic observation showed tumor cells were arranged in conglobate and nested by fibrous tissue with a visible cell atypia and mitotic. NEC-like and exocrine glandular cells were also been seen in a single neoplasm. MANEC tissues were immunopositive for CK, CK20, P53, CK7, CDX-2, Ki-67 (70%+), E-cad, CD56, CEA, Syn, villin and CgA, and immunonegative for CA125, NSE, ER and PR. Here, the patient was treated by surgical operation and was followed-up near 3 months, no local recurrence and distant metastasis.


Subject(s)
Adenocarcinoma/pathology , Carcinoma, Neuroendocrine/pathology , Colonic Neoplasms/pathology , Intestinal Mucosa/pathology , Neoplasms, Complex and Mixed/pathology , Adenocarcinoma/chemistry , Adenocarcinoma/surgery , Aged , Biomarkers, Tumor/analysis , Biopsy , Carcinoma, Neuroendocrine/chemistry , Carcinoma, Neuroendocrine/surgery , Colectomy , Colonic Neoplasms/chemistry , Colonic Neoplasms/surgery , Female , Humans , Immunohistochemistry , Intestinal Mucosa/chemistry , Neoplasm Invasiveness , Neoplasms, Complex and Mixed/chemistry , Neoplasms, Complex and Mixed/surgery , Treatment Outcome
6.
World J Gastroenterol ; 19(40): 6876-82, 2013 Oct 28.
Article in English | MEDLINE | ID: mdl-24187464

ABSTRACT

AIM: To investigate the association between nuclear ß-catenin overexpression in rectal adenocarcinoma and radioresistance. METHODS: A retrospective analysis was conducted. The analysis involved 136 patients with locally advanced rectal adenocarcinoma who underwent short-course preoperative radiotherapy and radical resection. The expression of ß-catenin in both pretreatment biopsy specimens and resected primary tumor tissues was examined by immunohistochemistry. The correlation of ß-catenin expression with radioresistance was evaluated using the tumor regression grading (TRG) system. The relationship between ß-catenin expression and clinicopathological characteristics was also analyzed. Univariate and logistic multivariate regression analyses were adopted to determine the independent factors of radioresistance. RESULTS: Nuclear ß-catenin overexpression was more evident in radioresistant rectal adenocarcinoma than in radiosensitive rectal adenocarcinoma (57.6% vs 16.7%, P < 0.001). Nuclear ß-catenin was overexpressed in favor of poor TRG (≤ 2), whereas membrane ß-catenin was expressed in favor of good TRG (≥ 3). Nuclear ß-catenin expression in tumor cell differentiation (P = 0.018), lymph node metastasis (P = 0.022), and TRG (P < 0.001) showed significant differences. Univariate analyses demonstrated that radioresistance is associated with nuclear ß-catenin overexpression (P < 0.001). In addition, logistic multivariate regression analysis indicated that only three factors, namely, tumor size (P < 0.001), tumor cell differentiation (P < 0.001), and nuclear ß-catenin overexpression (P < 0.001), are associated with radioresistance. By using radioresistance as a prediction target, nuclear ß-catenin-based prediction alone achieved 83% accuracy, 65% sensitivity, and 88% specificity. CONCLUSION: Nuclear ß-catenin overexpression may be a valuable candidate to predict the response of rectal adenocarcinoma to preoperative radiotherapy.


Subject(s)
Adenocarcinoma/radiotherapy , Biomarkers, Tumor/metabolism , Cell Nucleus/metabolism , Neoadjuvant Therapy , Radiation Tolerance , Rectal Neoplasms/radiotherapy , beta Catenin/metabolism , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Adult , Aged , Cell Differentiation , Chi-Square Distribution , Dose Fractionation, Radiation , Female , Humans , Logistic Models , Male , Middle Aged , Multivariate Analysis , Neoplasm Grading , Odds Ratio , Radiotherapy, Adjuvant , Rectal Neoplasms/metabolism , Rectal Neoplasms/pathology , Rectal Neoplasms/surgery , Retrospective Studies , Risk Factors , Treatment Outcome , Tumor Burden , Up-Regulation
7.
Article in Chinese | MEDLINE | ID: mdl-24044222

ABSTRACT

OBJECTIVE: To analyze the infection of human parvovirus B19, human bocavirus (HBoV) and human parvovirus 4 (PARV4) in blood samples among patients with liver disease in Nanjing by molecular detection. METHODS: Nested PCR assays were designed and validated to detect B19, HBoV and PARV4, respectively. The assays were used to screen three parvoviruses in blood samples from 95 patients with different liver disease in Nanjing. The parvovirus infection was analyzed statistically. RESULTS: The detection limits were 10 copies of genomic DNA equivalents per reaction for each assays and the good specificity were observed. The frequency of B19 and HBoV were 2/95 (2.1%) and 9/95 (9.5%) in blood samples respectively. No PARV4 was detected. HBoV was detected in 3/5 patients with drug-induced hepatitis. CONCLUSION: Both B19 and HBoV infection were detected in blood from patients with liver disease.


Subject(s)
Coinfection/virology , Human bocavirus/isolation & purification , Liver Diseases/virology , Parvovirus B19, Human/isolation & purification , Parvovirus/isolation & purification , Viremia/virology , Adolescent , Adult , Aged , Child , Female , Humans , Male , Middle Aged , Polymerase Chain Reaction
8.
Bing Du Xue Bao ; 28(4): 324-9, 2012 Jun.
Article in Chinese | MEDLINE | ID: mdl-22978154

ABSTRACT

A transient four-plasmid cotransfection system was used to construct avian influenza A (H5N1) pseudotyped viral particle (H5N1Pp) by incorporating hemagglutinin (HA) protein and neuraminidase (NA) protein from H5N1 avian influenza virus onto Murine leukemia virus pseudotyped viral particles, the transmission electron microscopy, infectivity titer assay, hemagglutination assay, neutralization assay of H5N1Pp were studied. We established a pseudotyped H5N1 viral particle at a high titer of 10(8) Pp/mL, the morphology,the hemagglutination activity and neutralization specificity of H5N1Pp is simililar to wild H5N1 virus. The research result sets a platform for studying this virus, including its receptors, the functional analysis of HA and NA, neutralizing antibodies and anti-H5N1 drug development.


Subject(s)
Genetic Engineering , Hemagglutinin Glycoproteins, Influenza Virus/genetics , Influenza A Virus, H5N1 Subtype/genetics , Influenza A Virus, H5N1 Subtype/physiology , Influenza in Birds/virology , Viral Load/genetics , Virion/genetics , Animals , Birds , Cricetinae , HEK293 Cells , Hemagglutination , Humans , Neutralization Tests , Transfection
9.
J Neuroimmunol ; 220(1-2): 25-33, 2010 Mar 30.
Article in English | MEDLINE | ID: mdl-20117842

ABSTRACT

Successive electroacupuncture (EA) stimulation on Zusanli ST36 acupoints of rats with experimental autoimmune encephalitis (EAE), which is an inflammatory disease mediated by autoreactive T cells, relieved disease severity, inhibited specific T cell proliferation and rebuilt the CD4+ T cell subset balance. In addition, EA-treated rats had significantly higher ACTH concentrations in vivo compared to untreated EAE rats. These results indicated that EA stimulation could relieve the severity of EAE by restoring balance to the Th1/Th2/Th17/Treg Th cell subset responses by stimulating the hypothalamus to increase ACTH secretion.


Subject(s)
Electroacupuncture/methods , Encephalomyelitis, Autoimmune, Experimental/immunology , Encephalomyelitis, Autoimmune, Experimental/therapy , Immune Tolerance/physiology , Immunosuppression Therapy/methods , T-Lymphocytes/immunology , Acupuncture Points , Adrenocorticotropic Hormone/blood , Adrenocorticotropic Hormone/metabolism , Animals , Cell Count , Cell Proliferation , Chemotaxis, Leukocyte/immunology , Disease Models, Animal , Encephalomyelitis, Autoimmune, Experimental/physiopathology , Female , Hypothalamus/metabolism , Lymphocyte Activation/immunology , Rats , Rats, Inbred Lew , T-Lymphocytes, Helper-Inducer/immunology , T-Lymphocytes, Helper-Inducer/metabolism , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/metabolism , Th1 Cells/immunology , Th1 Cells/metabolism , Th2 Cells/immunology , Th2 Cells/metabolism , Treatment Outcome
10.
Zhonghua Zhong Liu Za Zhi ; 31(8): 622-5, 2009 Aug.
Article in Chinese | MEDLINE | ID: mdl-20021952

ABSTRACT

OBJECTIVE: To investigate the correlation of radiation pneumonitis (RP) with standardized uptake value (SUV) for fluorodeoxyglucose (FDG) positron emission tomography and computed tomography (PET-CT) in lung cancer patients treated with radiation therapy. METHODS: Fourty patients with unresectable non-small cell lung cancer (NSCLC) received FDG PET-CT before and after radiotherapy. The average SUV of the lung tissue irradiated with a dose of < or = 5 Gy, 5.1 approximately 15 Gy, 15.1 approximately 35 Gy, 35.1 approximately 60 Gy, >60 Gy were measured. The correlation between SUV and RP was analyzed by comparing the SUV in the patients with RP and without. The SUV ratio of the irradiated lung tissue to that of the non-irradiated lung tissue (L/B) was also calculated. RESULTS: Of the 40 patients, 8 developed RP, including 6 cases of grade 2 and 2 cases of grade 3. The SUV of irradiated lung tissues with a dose of 35.1 approximately 60 Gy was significantly correlated with RP. When SUV > or =1, the RP incidence rate was 41.7% versus 20.0% in the whole group, with a statistically significant difference. (chi2 = 3.96, P < 0.05). The sensitivity and specificity of SUV in predicting RP was 62.5% and 78.1%, respectively. When the value of L/B > or = 2.5, the RP incidence rate was 40.7% in this group versus 20.0% in the whole group, with a statistical significance (chi(2) = 4.92, P < 0.05). If taking L/B > or = 2.5 as a threshold value, the sensitivity and specificity in predicting RP was 72.7% and 90.9%, respectively. No statistically significant difference was found in predicting radiation pneumonitis between SUV > or =1 and L/B > or = 2.5 (chi2 = 0.002, P > 0.05). CONCLUSION: The standardized uptake value (SUV) and the SUV ratio of the irradiated lung tissue to that of the non-irradiated lung tissue (L/B) for FDG PET-CT are positively correlated with radiation pneumonitis, and clinicians may use it to predict the occurrence of radiation pneumonitis.


Subject(s)
Carcinoma, Non-Small-Cell Lung/radiotherapy , Lung Neoplasms/radiotherapy , Radiation Pneumonitis/diagnosis , Radiotherapy, Conformal/adverse effects , Adult , Aged , Aged, 80 and over , Female , Fluorodeoxyglucose F18/pharmacokinetics , Follow-Up Studies , Humans , Male , Middle Aged , Positron-Emission Tomography , Radiation Dosage , Radiation Pneumonitis/etiology , Radiation Pneumonitis/metabolism , Radiopharmaceuticals/pharmacokinetics , Tomography, X-Ray Computed
11.
Int J Pharm ; 352(1-2): 29-35, 2008 Mar 20.
Article in English | MEDLINE | ID: mdl-18053659

ABSTRACT

This study is concerned with preparing PLGA nanoparticles loaded with voriconazole (PNLV), investigating the burst release and agglomeration of PNLV, and also evaluating antifungal efficacy of PNLV compared with voriconazole (VRC). The emulsion-solvent evaporation technique for nanoparticles and tests against fungi were completed. The amount of VRC in PNLV with sodium hexametaphosphate was 2.01+/-0.27%, and burst release of PNLV was reduced by about 33% using 20% ethanol solution (n=3). The mean D(50) of PNLV with or without this salt was 132.8 nm and 6.3 microm, respectively (n=5). In vitro; the fungal numbers treated with PNLV (3.5 mg/ml, equal amount calculated by VRC) and VRC (70 microg/ml) in tubes at the day 7 were 5.74 log(10) and 6.72 log(10), respectively (P<0.05). In vivo; the fungal burden treated with PNLV and VRC in tissue from mice kidneys at day 7 after administration was 0.64 log(10) and 2.61 log(10), respectively (5 mg/kg, P<0.001). The hematoxylin-eosin stain in mice kidney showed that the pathological lesions treated with PNLV were relieved in contrast with those with VRC. These results suggest that the emulsion-solvent evaporation process is feasible in preparing PNLV. Moreover, ethanol solution decreased burst release and Na-HMP inhibited agglomeration. PNLV could improve the VRC antifungal efficacy.


Subject(s)
Antifungal Agents/chemistry , Drug Carriers , Nanoparticles , Polyglactin 910/chemistry , Pyrimidines/chemistry , Triazoles/chemistry , Animals , Antifungal Agents/pharmacology , Candida albicans/drug effects , Candida albicans/growth & development , Chemistry, Pharmaceutical , Drug Compounding , Ethanol/chemistry , Feasibility Studies , Kidney/drug effects , Kidney/microbiology , Kinetics , Mice , Particle Size , Phosphates/chemistry , Pyrimidines/pharmacology , Solubility , Solvents/chemistry , Surface Properties , Technology, Pharmaceutical/methods , Triazoles/pharmacology , Voriconazole
12.
Zhonghua Nan Ke Xue ; 13(5): 428-30, 2007 May.
Article in Chinese | MEDLINE | ID: mdl-17569260

ABSTRACT

OBJECTIVE: To investigate the effect of nifedipine of therapeutic dosage on the plasma membrane functional integrity and osmosensitive calcium influx in human sperm in vitro. METHODS: Sperm samples were aseptically obtained from 10 healthy fertile men by masturbation and prepared by swim-up technique to produce a spermatozoal solution of high motility. The solution was then incubated with nifedipine of 20, 100 and 20 x 10(3) ng/ml respectively at 37 degrees C in vitro. The hypo-osmotic swelling (HOS) test was done to assess the sperm function. Intracellular calcium concentration was measured by fluorescent probe fura-2/AM before and after sperm medium dilution in distilled water. RESULTS: The 20 x 103 ng/ml group showed significantly lower HOS scores than the control (P < 0.01). The 20, 100 and 20 x 10(3) ng/ml groups all showed significantly lower Ca2+ fluorescence D-value than the control (P < 0.01). CONCLUSION: Nifedipine can modify plasma membrane functional integrity and inhibit osmosensitive calcium influx in human sperm and affect male fertility in vitro in therapeutic dose.


Subject(s)
Calcium/metabolism , Nifedipine/pharmacology , Spermatids/drug effects , Spermatids/physiology , Adult , Cell Membrane , Humans , In Vitro Techniques , Male , Osmotic Pressure , Spermatids/metabolism
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