ABSTRACT
Objective: To investigate the short-term efficacy and adverse events of chemotherapy combined with androgen-deprivation therapy in high-volume metastatic hormone sensitive prostate cancer. Methods: From March 2015 to August 2017, 55 patients with high-volume metastatic hormone sensitive prostate cancer were enrolled at Department of Urology, Fudan University Shanghai Cancer Center receiving chemotherapy combined with androgen-deprivation therapy. The age was 65(8) years (M(Q(R))) (range: 46 to 79 years). Patients were enrolled in the study for continuous androgen-deprivation therapy (medical or surgical castration), combined with docetaxel 75 mg/m(2) intravenous injection on the first day, repeated every 21 days (6 cycles). Endpoints included overall survival, progression-free survival of prostate cancer, prostate specific antigen (PSA) response rate, and adverse events. Results: The follow-up time was 21.2(11.7) months. The PSA value before chemotherapy was 144.9(415.3) µg/L. The days in patients undergoing androgen deprivation therapy before chemotherapy was 14(23) days. Four patients (7.3%) presented 0 in Eastern Cooperative Oncology Group scoring system and 51 patients(92.7%) presented 1. Thirty-nine patients (70.9%) completed more than 6 cycles of combined chemotherapy, 17 patients (30.9%) showed PSA<0.2 µg/L at 6 months after treatment, and 14 patients (25.5%) showed PSA<0.2 µg/L at 12 months after treatment. Twenty-eight patients (50.9%) had grade 3 to 4 neutropenia and 1 patient (1.8%) developed infectious neutropenia and died. Nausea and vomit occurred in 16 patients (29.1%). Twelve patients (21.8%) underwent dose adjustment due to adverse events in blood system. Conclusions: The short-term effect was confirmed in high-volume metastatic hormone sensitive prostate cancer using chemotherapy combined androgen-deprivation therapy, and the long-term effect remains to be seen. Myelosuppression during chemotherapy requires close attention, and taking timely examination is recommended.
Subject(s)
Antineoplastic Agents/therapeutic use , Docetaxel/therapeutic use , Prostatic Neoplasms/drug therapy , Aged , Androgen Antagonists/adverse effects , Androgen Antagonists/therapeutic use , Antineoplastic Agents/adverse effects , Biomarkers, Tumor/blood , Docetaxel/adverse effects , Humans , Male , Middle Aged , Orchiectomy , Prostate-Specific Antigen/blood , Prostatic Neoplasms/blood , Prostatic Neoplasms/surgery , Treatment OutcomeABSTRACT
Objective: To explore the feasibility of high-throughput texture analysis in the distinction of single brain metastases (SBM) from high-grade gliomas (HGG) and validate the established model. Methods: A total of 86 patients who were histologically diagnosed with SBM or HGG were retrospectively collected, including 43 patients with SBM and 43 with HGG. All of patients were performed preoperative conventional head magnetic resonance imaging (MRI) scans. A total of 236 fluid-attenuated inversion recovery (FLALR) images containing the information of tumors were selected from the MRI images and each image was considered as an object. The training set had 200 images, including 106 from SBM group and 94 from HGG group, whereas the validation set had 36 images, including 19 from SBM group and 17 from HGG. After images preprocessing, images segmentation, features extraction, and features selection, a radiomic diagnostic model was finally established using the training set. The diagnostic performance of the diagnostic model was evaluated using a receiver operating characteristic (ROC) curve. Hierarchical clustering analysis was used to evaluate the quality of the extracted feature data and the classification effect of the model. The model was further validated using the independent validation set. Results: A total of 629 features were extracted and quantified from each sample, and 41 features were selected to establish feature subsets and the diagnostic model. The classification decision function of the model is f(x)=signâ and the kernel function of the model is K(x, x(i))=expâ . In the training set, the diagnostic accuracy, sensitivity, specificity, positive predictive value and negative predictive value were 0.845, 0.849, 0.840, 0.857 and 0.832, respectively. The area under the ROC curve reached to 0.939. Similar results were obtained in the validation set. Conclusion: The high-throughput texture analysis shows high accuracy in differentiating SBM from HGG.
Subject(s)
Brain Neoplasms/diagnostic imaging , Glioma/diagnostic imaging , Magnetic Resonance Imaging/methods , Area Under Curve , Brain Neoplasms/pathology , Brain Neoplasms/secondary , Cluster Analysis , Diagnosis, Differential , Feasibility Studies , Glioma/pathology , Glioma/secondary , Humans , ROC Curve , Retrospective StudiesABSTRACT
OBJECTIVE: Based on our previous established cohort of myelodysplastic syndrome (MDS), we investigated the potential effect of beta-tubulin(TUBB) gene in the transformation of MDS into acute leukemia. METHODS: From our nested case-control study cohort of MDS patients, we chose 11 paired transformed and non-transformed MDS patients. TUBB gene expression was tested by quantitative real-time PCR. TUBB-siRNA transfection was used to down-regulate TUBB gene expression in SKM-1 cell line. The function of TUBB gene in SKM-1 cell line was evaluated by cell proliferation, soft agar clone formation and electron microscope. RESULTS: TUBB gene expression in MDS patients in transformed group were significantly higher than that in control group (2.91±0.41 vs 0.90±0.23, P<0.01). After TUBB-siRNA transfection, A450/630nm of SKM-1 cells at 24 h, 48 h and 72 h were 0.299±0.045, 0.526±0.034 and 0.652±0.035, respectively, which were significantly decreased than those in negative-siRNA group(0.438±0.074, 0.858±0.064 and 0.974±0.044)(P<0.05). Soft agar clone formation in TUBB-siRNA group was (7.0±0.2)%, which was significantly reduced than that of negative-siRNA group (25.0±0.2)% (P<0.01). Electron microscope showed significant apoptotic signs in TUBB-siRNA group, including vacuoles in cytoplasm and karyorrhexis. CONCLUSION: Our results indicate that TUBB gene may play a role in the transformation of MDS into acute leukemia by affecting the proliferation of malignant clones.
Subject(s)
Leukemia/genetics , Myelodysplastic Syndromes/genetics , Myelodysplastic Syndromes/pathology , RNA, Small Interfering , Transfection , Tubulin/genetics , Apoptosis , Bone Marrow Cells , Case-Control Studies , Cell Line , Cell Proliferation , Cohort Studies , Down-Regulation , Gene Expression Regulation, Leukemic , Humans , Leukemia/etiology , Leukemia/pathology , Myelodysplastic Syndromes/metabolism , RNA, Messenger/genetics , Real-Time Polymerase Chain ReactionABSTRACT
We propose a scheme to generate quantum entangling gate using one-dimensional surface plasmon waveguide. The protocol is based on the detection of the transmission spectrum of the single optical plasmons passing through two separate three-level emitters on metallic nanowire waveguide. It is shown that the low efficiency in direct detection of the single photon can be avoided by repeating the measurement of the transmission spectrum.
ABSTRACT
Aphids exhibit unique attributes, such as polyphenisms and specialized cells to house endosymbionts, that make them an interesting system for studies at the interface of ecology, evolution and development. Here we present a comprehensive characterization of the developmental genes in the pea aphid, Acyrthosiphon pisum, and compare our results to other sequenced insects. We investigated genes involved in fundamental developmental processes such as establishment of the body plan and organogenesis, focusing on transcription factors and components of signalling pathways. We found that most developmental genes were well conserved in the pea aphid, although many lineage-specific gene duplications and gene losses have occurred in several gene families. In particular, genetic components of transforming growth factor beta (TGFbeta) Wnt, JAK/STAT (Janus kinase/signal transducer and activator of transcription) and EGF (Epidermal Growth Factor) pathways appear to have been significantly modified in the pea aphid.
Subject(s)
Aphids/growth & development , Aphids/genetics , Genes, Insect , Amino Acid Sequence , Animals , Aphids/pathogenicity , Body Patterning/genetics , Female , Gene Deletion , Gene Duplication , Genes, Homeobox , Genome, Insect , Insect Proteins/genetics , Male , Molecular Sequence Data , Pisum sativum/parasitology , Phylogeny , Receptors, Cytoplasmic and Nuclear/genetics , Sequence Homology, Amino Acid , Signal Transduction/genetics , Transcription Factors/geneticsABSTRACT
This study was designed to evaluate the prevalence of fms-like tyrosine kinase-3 (FLT3) gene mutations in the World Health Organization classified subtypes of acute leukaemia (AL), and their prognostic significance in terms of complete remission (CR), leukaemia-free survival (LFS) and overall survival (OS). Of 468 patients, 374 (79.9%) had acute myeloid leukaemia (AML) and 83 (17.7%) had acute lymphoblastic leukaemia (ALL). Among the AML patients, a FLT3 internal tandem duplication (FLT3/ITD) mutation was present in 59 cases (15.8%), whereas a FLT3/D835 mutation was detected in 15 cases (4.0%). Conversely, in the ALL patients, no FLT3/ITD mutations were detected and a FLT3/D835 mutation was found in only two cases (2.4%). The FLT3/ITD mutation was associated with a lower CR rate compared with those with no mutations (52.3% versus 71.1%) and with a shorter median OS (9 versus 18 months) in AML patients. In conclusion, the FLT3/ITD mutation occurred frequently in AML and was associated with a lower CR and shorter median OS. In contrast, FLT3/D835 mutations were not of prognostic value.
Subject(s)
Biomarkers, Tumor/genetics , Leukemia, Myeloid, Acute/genetics , Mutation/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , fms-Like Tyrosine Kinase 3/genetics , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Humans , Immunoenzyme Techniques , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/pathology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Prevalence , Prognosis , Survival RateABSTRACT
A scheme is presented to realize a single-photon transistor based on cavity quantum electrodynamics (QED) with Rydberg atomic ensemble. By combining the advantages of the cavity-enhanced interaction and Rydberg blockade, we achieve a high gain single-photon transistor. The numerical calculation shows that by using one single gate photon more than one thousand source photons can be switched.
ABSTRACT
The S-adenosylmethionine synthetase activities of rat liver and Novikoff ascites tumor have been partially purified and characterized by chromatographic behavior, kinetic analysis, sulfhydryl dependency, and response to inhibitors. We have shown that the tumor contains a single form of the enzyme, with a Km (methionine) of 21 muM, and that the liver contains two isofunctional forms, a minor form with a Km (methionine) of 21 muM, as well as a major form with a Km of 1 mM. The tumor contained more of the low Km form of the enzyme than the liver, although the total enzyme activity of liver (measured at high substrate concentrations) exceeded that of the tumor severalfold. The tumor enzyme also corresponded to the minor form of liver enzyme in elution position from Sephadex G-150 and diethylamino-ethyl cellulose, and both had a Km (adenosine 5'-triphosphate) of 0.14 mM. The tumor enzyme differed from the major form of the liver enzymes in elution position, and the Km (adenosine 5'-triphosphate) for the latter was 1.5 mM. In contrast to the major liver enzyme, the tumor enzyme did not appear to require sulfhydryl agents for the activity to be detected, was inhibited by S-adenosylmethionine, and was inhibited to a greater degree by tripolyphosphate. It is suggested that the two forms of the enzyme are involved in the production of S-adenosylmethionine for different biological functions, and their different properties may allow selective inhibition of tumor growth by chemotherapeutic agents.
Subject(s)
Carcinoma, Hepatocellular/enzymology , Liver Neoplasms/enzymology , Liver/enzymology , Methionine Adenosyltransferase/metabolism , Transferases/metabolism , Animals , Female , In Vitro Techniques , Kinetics , Methionine/metabolism , Methionine Adenosyltransferase/antagonists & inhibitors , Methionine Adenosyltransferase/isolation & purification , Neoplasms, Experimental/drug therapy , Neoplasms, Experimental/enzymology , Phosphates/pharmacology , Rats , tRNA Methyltransferases/metabolismABSTRACT
Quantum controlled-phase-flip (CPF) gate between a flying photon qubit and a stationary atomic qubit could allow the linking of distant computational nodes in a quantum network. Here we present a scheme to realize quantum CPF gate between a flying optical photon and an atomic ensemble based on cavity input-output process and Rydberg blockade. When a flying single-photon pulse is reflected off the cavity containing a Rydberg atomic ensemble, the dark resonance and Rydberg blockade induce a conditional phase shift for the photon pulse, thus we can achieve the CPF gate between the photon and the atomic ensemble. Assisted by Rydberg blockade interaction, our scheme works in the N-atoms strong-coupling regime and significantly relaxes the requirement of strong coupling of single atom to photon in the optical cavity.
ABSTRACT
The influence of ethanol feeding during pregnancy on histamine excretion was studied. Pregnant Sprague-Dawley rats (N = 5) were fed a liquid diet containing 30% ethanol-derived calories from gestation-day 7 to 21; control rats (N = 5) were pair-fed with isocaloric sucrose substituted for ethanol. Twenty-four hour urines were collected for histamine analysis. Rats were killed on day 21 of gestation. Food and ethanol intakes averaged 260 kcal and 11 g/kg/day, respectively. No differences were found between ethanol and control rats in maternal weight gain, litter size or in fetal and placental weights. Although urinary histamine increased in all rats with the advance of pregnancy, on day 16, ethanol rats excreted significantly more (47%) than the controls (199.1 +/- 33.9 vs 135.5 +/- 51.4 ug/24 hr); on day 20, it was 123% more (534.6 +/- 114.4 vs 239.5 +/- 99.3 ug/24 hr). Ethanol enhanced urinary histamine did not reflect the histamine content or histidine decarboxylase activity of fetal liver, presumed site of histamine formation; its physiological significance is discussed.
Subject(s)
Ethanol/toxicity , Fetus/drug effects , Histamine/urine , Animals , Female , Fetus/metabolism , Histidine Decarboxylase/analysis , Liver/enzymology , Pregnancy , Rats , Rats, Inbred StrainsABSTRACT
The effects of acute ethanol treatment and dietary folate deficiency on maternal-fetal folate transfer were studied to asses the hypothesis that the potentiation of ethanol's toxic effect on the fetus during ongoing folate deficiency was due to the impairment of folate transfer. Sprague-Dawley rats were fed either a folate-deficient diet (0.2 mg/kg) or a folate-sufficient diet (2 mg/kg) for an average of 11 weeks before pregnancy and continued until gestation day 11 when they were sacrificed. On gestation day 11, pregnant rats were treated with either ethanol (2.5 g/kg body weight) or isocaloric sucrose (control) followed by an intravenous administration of 3H-folate (2 muCi/100 g body weight) at 120 minutes. At 210 minutes, maternal blood and feto-placental tissues were removed for radioactivity measurement. Folate status and ethanol treatment had no effect on the distribution of 3H-folate in maternal circulation. However, contrary to the hypothesis, the uptake of 3H-folate by feto-placental tissues was increased in folate deficiency and by ethanol treatment, indicating that folate transfer was not impaired by the ethanol treatment. Other possibilities are discussed.
Subject(s)
Ethanol/pharmacology , Folic Acid Deficiency/metabolism , Folic Acid/metabolism , Maternal-Fetal Exchange/drug effects , Animals , Diet , Female , Fetus/metabolism , Folic Acid/administration & dosage , Folic Acid/blood , Placenta/metabolism , Pregnancy , Rats , Rats, Inbred StrainsABSTRACT
Equilibration of ethanol between dorsal subcutaneous air and blood is rapid, a steady state being already present in 60 seconds after air injection in the rat. The mean in vivo partition coefficient (blood/air) is 2,875, the linear regression coefficient having a standard error of 112, the high F value of this regression indicating the linearity and reliability of the estimates of calculated blood ethanol; the variance arises mainly from temperature variance of the air bleb. Although the concentration of alcohol in the blood must remain the standard of comparison, the production of the air bleb and its subsequent serial sampling is a virtually noninvasive technique which yields an almost immediate result at a sensitivity and specificity greater than that from the usual enzymatic determination of ethanol in blood.
Subject(s)
Air/analysis , Ethanol/metabolism , Animals , Ethanol/blood , Male , Methods , Rats , Skin , TemperatureABSTRACT
The rate of ethanol metabolism and the extrapolated zero time blood ethanol concentration (C0) were compared in naive and ethanol-fed rats following intracardiac or ingastric administration of a test dose of ethanol (3 g/kg). If the gastrointestinal tract is involved in the disposition of ethanol, intragastric administration should result in a lower C0 and a faster overall rate of metabolism than intracardiac administration, since part of the dose would be metabolized in the gastrointestinal tract without having been absorbed and thereby entering the blood. However, no significant differences were observed in C0. The rate of metabolism was substantially higher in the ethanol-fed rats, but was uninfluenced by route of administration. Thus, the gastrointestinal tract plays no significant role in the metabolism of ethanol.
Subject(s)
Digestive System/metabolism , Ethanol/metabolism , Alcohol Drinking , Animals , Body Weight/drug effects , Eating , Ethanol/blood , Male , Oxidation-Reduction , RatsABSTRACT
POEMS syndrome is an unusual multisystem disorder associated frequently with polyneuropathy, organomegaly, endocrinopathy, M-protein change and skin lesion. POEMS is the acronym the above-mentioned clinical manifestations. The patients who were diagnosed must have at least three of the manifestations; polyneuropathy and plasmagenic disorders are almost always present. We present in this paper eight patients, their clinical symptoms, laboratory tests and treatment were analysed and discussed.
Subject(s)
POEMS Syndrome/diagnosis , Adult , Female , Humans , Male , Middle Aged , POEMS Syndrome/therapy , Prognosis , Tamoxifen/therapeutic useABSTRACT
Erythrocyte basic ferritin (EF) concentration was determined in 64 normal subjects, 123 patients with anemia and 12 patients with leukopenia and thrombocytopenia. There was a significant difference between males and females. Other iron indices, including plasma iron (PI), total iron binding capacity (TIBC), zinc protoporphyrin (ZnPP) and plasma ferritin (PF) were also determined in all the subjects and bone marrow iron stain was determined in the 135 patients. The lowest EF concentration was seen in patients with iron deficiency anemia, being significantly lower than that in normal subjects. EF concentration in patients with iron deficiency erythropoiesis was also lower than that in normal subjects and at the same time significantly different from that in patients with iron deficiency anemia. EF concentration increased prior to PF concentration in patients with iron deficiency anemia who had been treated for a period of 1-8 weeks. EF concentration in patients with anemia of chronic diseases had a significant difference as compared with that in normal subjects and in patients with iron deficiency anemia, but EF concentration in those patients who were accompanied by iron deficiency was similar to that in patients with simple iron deficiency anemia. EF concentration in some iron overloaded patients (aplastic anemia, megaloblastic anemia, MDS etc.) was significantly higher than that in normal subjects. It was demonstrated that there was a good correlation between EF concentration and bone marrow sideroblastic iron in the rank correlation analysis of the iron indices in 135 patients (rs 0.893, P less than 0.01). PF concentration had the best correlation with marrow iron (rs 0.948, P less than 0.01).
Subject(s)
Anemia/diagnosis , Erythrocytes/chemistry , Ferritins/blood , Adolescent , Adult , Aged , Anemia/blood , Anemia, Hypochromic/blood , Anemia, Hypochromic/diagnosis , Female , Humans , Male , Middle AgedABSTRACT
BACKGROUND: Controversial data on the association of single-nucleotide polymorphisms (SNPs, rs3787016G>A and rs10773338G>A) in long non-coding RNA (lncRNA) with prostate cancer risk were emerged. Considering possible genetic differences among populations, we conducted the present study to clarify these discrepancies and re-validate these results in an eastern Chinese population and thus provide clues for new therapeutic targets of prostate cancer. METHODS: Genotypes of these two SNPs from 1015 ethnic Han Chinese patients with prostate cancer and 1032 cancer-free controls were determined by Taqman assays. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for risk associations. RESULTS: The association of rs3787016 A variant genotypes with a significantly higher prostate cancer risk were found (adjusted OR = 1.418, 95% CI = 1.090-1.844 for AA vs GG). Stratification analysis indicated that the risk of rs3787016 variant AG/AA genotypes was more evident in younger subjects, ever smoking, patients with Gleason score ⩾ 7(4+3) and highly aggressive status. All these risks were not present for rs10773338G>A. CONCLUSIONS: These findings suggested that lncRNA SNPs may contribute to prostate cancer risk in an eastern Chinese population. Larger and well-designed studies with different ethnic populations are warranted to validate our findings.