Electrophoretic deposition polymerization of diacetylenes with tunable structure.

Serial novel chiral polydiacetylenes (PDAs) are efficiently prepared at room temperature by the controllable electrophoretic deposition of diacetylenes with tunable structure as designed from easily available starting materials. The colorimetrically reversible properties of PDAs in the range between 25 and 85 °C are influenced by the different amino acid moiety in the PDAs as anticipated. The PDA containing aromatic ring is much better for the colorimetrically reversible properties, while irreversible thermochromism is displayed for the PDA with the structure of the longer methylene units in the main chain of amino acid moiety.

Anticancer Activity of New Na(I) Complex on Retinoblastoma Cells via Inhibiting PI3K/AKT/mTOR Pathway.

Here, through applying 2,6-bis(4'-carboxyl-phenyl)pyridine (H2L), a rigid ligand featuring both carboxylic acid and pyridine groups, a new coordination polymer containing Na(I) has been generated with the reaction between H2L ligand and NaNO3 in a water and DMF mixed solvent, and its chemical composition is [Na2L]n. Furthermore, the antiproliferative activity of Na(I) complex against the HXO-Rb44 retinoblastoma cells was detected with CCK-8 assay. Hoechst staining along with Annexin V-FITC/PI revealed that Na(I) complex induces the HXO-Rb44 retinoblastoma cells apoptosis. Flow cytometry analysis of reactive oxygen species (ROS) showed that Na(I) complex significantly increases the level of intracellular ROS. Importantly, western blot analysis revealed that Na(I) complex might induce apoptosis through inactivation of PI3K/AKT/mTOR pathway.

[Clinicopathological analysis of nine cases of small cell carcinoma of the uterine cervix].

OBJECTIVE: To investigate the clinicopathologic characteristics, therapy and prognostic factors of small cell carcinoma of the uterine cervix (SCCC). METHODS: Nine patients with SCCC underwent radical hysterectomy at the Cancer Hospital of CAMS between 2000 to 2009. Clinical and pathological data were analyzed, and the related literature was reviewed. RESULTS: The average age of 9 patients was 41 years old. Irregular vaginal bleeding and postcoital spotting were the most common symptoms. According to FIGO staging criteria, six patients were stage Ib1 disease, 2 stage Ib2 and 1 stage IVb. All tumors were composed of small-sized cells with scant cytoplasm, darkly stained round to oval nuclei, finely dispersed chromatin and absence of nucleoli. High mitotic activity and lymphovascular invasion were also common findings. Immunohistochemical staining showed at least three neuroendocrine markers (NSE, CgA, Syn and CD56) were positive in each case. All patients received postoperative chemotherapy, with or without radiotherapy. Seven patients remained alive 6 to 104 months and one died 14 months postoperatively. CONCLUSION: SCCC is a highly malignant tumor with aggressive behavior. Correct diagnosis of SCCC depends on the combination of light microscopic and immunohistochemical analysis. It is necessary to use multimodality treatment for SCCC, especially the chemotherapy. However, the prognosis is dismal.

[An analysis of 100 cases of tuberculosis first presenting as fever of unknown origin in a general tertiary hospital].

OBJECTIVE: To investigate the clinical characteristics of tuberculosis (TB) first presenting as fever of unknown origin (FUO). METHODS: The clinical data of 100 cases of FUO, diagnosed as TB finally, among in-patients in Peking Union Medical College Hospital were analyzed retrospectively. RESULTS: (1) Sites of TB:there were 39 patients with merely pulmonary TB, 28 patients with merely extrapulmonary TB, and 33 patients with both pulmonary and extrapulmonary TB. (2) CLINICAL MANIFESTATIONS: depending on the different sites of tuberculous lesion, the clinical symptoms varied accordingly. The common laboratory findings included anemia, hypoalbuminemia, elevation of the level of ESR and C-reactive protein (CRP). (3) Methods for diagnosis: 34 cases were diagnosed by sputum smear- or cultivation-positive for acid-fast bacilli; 8 cases by histopathology; 49 cases by clinical diagnosis of TB with an effective anti-TB therapy; and 9 cases by effective diagnostic anti-TB therapy. (4) Responses to treatment: among 73 cases with complete follow-up data, only 2 cases (2.7%) died and the other cases were cured or alleviated. Fifty-five cases (77.5%) showed marked efficacy after less than 4 weeks of regular anti-TB therapy, 37 cases (52.1%) suffered adverse effects of anti-TB agents, and all of them had improved after modifying anti-TB therapy and supporting treatment. CONCLUSIONS: The diagnosis of TB that presents as FUO is quite difficult, and the median interval time for making diagnosis is 14 weeks (3 - 77 weeks). Investigating clinical manifestations comprehensively, reviewing radiology data carefully, and eliciting microbiological and pathologic evidence of TB, are extremely important for making the correct diagnosis. In some cases, a therapeutic trial of anti-TB therapy is necessary.

[A clinical analysis of 25 cases of prosthetic valve endocarditis].

OBJECTIVE: To report the clinical characteristics of prosthetic valve endocarditis (PVE). METHODS: All 25 cases of definite PVE (Duke criteria) diagnosed at our hospital between January 1992 to December 2008 were retrospectively analyzed. Among them, 7 cases were pathologically confirmed and the others were clinically confirmed with either 2 major criteria or 1 major and ≥ 3 minor criteria. Their clinical characteristics, underlying heart diseases, previous heart operations, presenting manifestations, causative microbes, echocardiographic findings and prognosis, were studied. RESULTS: (1) Although most cases underwent valve transplantations for underlying heart diseases of rheumatic heart diseases and congenital heart diseases, 10 patients were complicated with infectious endocarditis (IE) prior to the operations, 4 of them were PVE. (2) Eleven of them developed PVE within 2 months postoperatively. Fever (100%), major vessel embolism (48%), and anemia (36%) were the most frequently manifestations. Fourteen cases (56%) had positive culture results with 15 causative pathogens, including 5 coagulase-negative Staphylococcus (CNS, 3 were methicillin-resistant coagulase-negative Staphylococcus, MRSCoN), 4 fungi, 2 Enterococcus faecalis, 2 Burkholderia cepacia, 1 Stenotrophomonas maltophilia, and 1 Streptococcus. (3) Prosthetic valve vegetations, periannular leakage, regurgitation, were the main echocardiographic findings. Transesophageal echocardiography (TEE) revealed 13 PVE who had no positive findings on previous transthoracic echocardiography (TTE). (4) Eighteen PVE (72%) developed peri-annular complications (12 leakage, 3 dehiscence, 2 abscesses, 1 fistula), major vessel embolism, congestive heart failure (16%) were frequently observed, 9 of the 17 patients died in hospital, in spite of intensive managements. CONCLUSIONS: PVE has a high mortality and is a severe complication for patients who underwent heart surgery. Its causative pathogen spectrum is quite different from that of native valve endocarditis. TTE is not sensitive for some PVE cases.

A novel one-dimensional zinc coordination polymer containing 4-methylbenzoate and 4,4-bipyridine.

The title compound, catena-poly[[tris(mu-4-methylbenzoato)-kappa(2)O:O;kappa(4)O:O'-(4-methylbenzoato-kappa(2)O,O')dizinc(II)]-mu-4,4'-bipyridine-kappa(2)N:N'], [Zn(2)(C(8)H(7)O(2))(4)(C(10)H(8)N(2))](n), is a novel coordination polymer. The asymmetric unit contains two unique Zn(II) ions, four 4-methylbenzoate ligands and one 4,4'-bipyridine (4,4'-bpy) ligand, all in general positions. The four 4-methylbenzoate ligands link the two Zn(II) centres to form a dinuclear unit, with a Zn...Zn separation of 3.188 (2) A, which can be regarded as a supramolecular secondary building unit (SBU). These SBUs are further bridged by 4,4'-bpy ligands, forming a novel one-dimensional infinite chain. There are pi-pi stacking interactions between the benzene rings of the 4-methylbenzoate ligands and the pyridyl rings of the 4,4'-bpy ligands, leading to the formation of a corrugated layer. These layers are further assembled via C-H...O hydrogen bonds into a three-dimensional supramolecular network structure. Coordination polymers such as the title compound are of interest for their potential applications as functional materials.

Bis(2,2'-bipyridine-κN,N')(4-methyl-benzoato-κO,O')copper(II) iodide hemihydrate.

The title compound, [Cu(C(8)H(7)O(2))(C(10)H(8)N(2))(2)]I·0.5H(2)O, was obtained by the hydro-thermal reaction of copper(I) iodide, 4-methyl-benzoic acid and 2,2'-bipyridine. The initial reactant of Cu(I) was oxidized to Cu(II). The asymmetric unit contains two independent complex mol-ecules, two I(-) ions and one water molecule. Each Cu(II) atom is coordinated by two O atoms from a 4-methyl-benzoate ligand and four N atoms from two 2,2'-bipyridine ligands, displaying a distorted octa-hedral geometry. The structure involves O-H⋯I hydrogen bonds between the water mol-ecule and iodide ions and π-π stacking inter-actions between the benzene and pyridyl rings [centroid-centroid distance = 3.79 (1) Å] and between the pyridyl rings [centroid-centroid distance = 3.87 (1) Å].

Diaqua-bis(4-methyl-benzoato-κO)zinc(II).

The Zn atom in the title mononuclear complex, [Zn(C(8)H(7)O(2))(2)(H(2)O)(2)], lies on a special position of site symmetry 2. The carboxyl-ate group binds in a monodentate manner so that the geometry is best described as tetra-hedral. Adjacent mol-ecules are linked by O-H⋯O hydrogen bonds into a three-dimensional network.

Epidemic of wild-origin H1NX avian influenza viruses in Anhui, China.

BACKGROUND: As the natural hosts of avian influenza viruses (AIVs), aquatic and migratory birds provide a gene pool for genetic transfer among species and across species, forming transient "genome constellations." This work describes the phylogenetic dynamics of H1NX based on the complete molecular characterization of eight genes of viruses that were collected from 2014 to 2015 in Anhui Province, China. METHODS: Hemagglutination and hemagglutination inhibition tests were used to determine the hemagglutination (HA) activity of the HA subtypes. The entire genomes of the viruses were sequenced on an ABI PRISM 3500xl DNA Analyzer. The sequences were genetically analysed to study their genetic evolution using DNASTAR and MEGA 6. The pathogenic effects of the viruses were evaluated using mouse infection models. RESULTS: Seven strains of the H1 subtype avian influenza virus were isolated. Phylogenetic analysis indicated natural recombination of the H1 influenza viruses between the Eurasian lineage and the North American lineage. Some genes had high sequence identity with A/bean goose/Korea/220/2011(H9N2), which is a typical case involving viral reassortment between the Eurasian lineage and the North American lineage. The results of infection experiments in mice showed that the viruses could acquire the ability to multiply in mouse respiratory organs without adaptation. CONCLUSIONS: These findings suggest that continued surveillance of wild birds, particularly migratory birds, is important to provide early warning of possible H1 influenza epidemics and to understand the ecology of the virus.

[Clinical characteristics of 143 Chinese HIV/AIDS patients].

OBJECTIVE: To investigate the clinical characteristics of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients in China. METHODS: Totally 143 HIV/AIDS patients who were first diagnosed in Peking Union Medical College Hospital form January 1988 to April 2006 were enrolled in this study. Clinical characteristics were retrospectively analyzed. RESULTS: Among 143 HIV/ AIDS patients, 57 patients had no clinical symptoms and were confirmed by routine examinations; 86 patients had clinical symptoms, including fever (n = 50), weight loss (n = 18), and discomforts involving respiratory system (n = 34), gastrointestinal system (n = 16), and derma and mucosa (n = 17). Opportunistic infections (OIs) such as pneumocystis jiroveci pneumonia (PCP) (n = 27), oropharyngeal candidiasis (n = 16), tuberculosis (n = 15) , and cytomegalovirus (CMV) infection (n = 9) were also observed in patients whose CD4 + T cell counts were less than 200/mm3. Most CMV infection and cryptococcal meningitis occurred in patients whose CD4 + T cell counts were less than 100/mm3. CD4 + T cell count was negatively correlated with plasma viral load (r = -0.420, P = 0.001). CONCLUSIONS: Fever, dyspnea, and weight loss are the most common symptoms in the patients of this study. The respiratory system, gastrointestinal system, derma and mucosa are the most commonly affected areas by OIs, and PCP is the most common OI. The occurrence of OIs corelates with CD4 + T cell count.

[A clinical analysis of 57 cases of abdominal tuberculosis].

OBJECTIVE: To explore the clinical characteristics and diagnosis methods of abdominal tuberculosis. METHODS: The clinical characteristics of abdominal tuberculosis in 57 cases proved by histopathology between 1958-2004 were retrospectively analyzed. RESULTS: There were 39 cases of tuberculosis of the liver, 5 cases of the spleen, 8 cases of the pancreas, 3 cases of the stomach, 1 case involved both liver and spleen and 1 case involved both liver and stomach. Twenty-six patients were males and 31 female; with ages ranged from 17 to 68 years (mean 40.7 years) and most cases (71.9%) having extra-abdominal tuberculosis. Fever (75.4%), fatigue, anorexia, night sweating, weight loss (82.5%) and hepatosplenomegaly (57.9%) were the major clinical manifestations. Elevated erythrocyte sedimentation rate (ESR) (59.6%) and abdominal mass (64.9%) were found in most of the patients. CONCLUSIONS: The diagnosis of abdominal tuberculosis should be considered in all patients with fever of unknown origin, especially in those associated with hepatosplenomegaly, increased ESR and abdominal mass. Aspiration biopsy and laparotomy can provide correct diagnosis. The disease can be effectively treated with surgical intervention and antituberculous chemotherapy.

[A clinical analysis of 22 cases of Pneumocystis pneumonia in acquired immunodeficiency syndrome].

OBJECTIVE: To investigate the clinical characteristics, therapeutical approaches and outcome of Pneumocystis pneumonia (PCP) in patients with AIDS. METHODS: The clinical data of 22 PCP patients with AIDS who were treated in Peking Union Medical College Hospital from January 1992 to October 2004 were analyzed, including the routes of HIV infection, clinical profiles, immunological status, chest radiological characteristics, therapeutic managements and outcome. RESULTS: (1) Of the 22 PCP patients, 16 were male and 6 female. The average age was (35.0 +/- 9.4) years old. The majority of patients got HIV infection through blood transfusion (54.5%) and sexual transmission (27.3%). (2) The common clinical presentations were fever (21/22), progressive exertional dyspnea (20/22), cough (16/22), sputum (12/22) and weight loss (18/22). 68.2% (15/22) of the patients had normal or mild coarse breath sounds on auscultation. 14 patients had an PaO(2) less than 60 mm Hg (1 mm Hg = 0.133 kPa). (3) All the 22 PCP cases were in their late stage of AIDS. For the 20 patients who had an immunological test, the peripheral CD(4)(+) T lymphocyte count was ranging from 3 x 10(6)/L to 148 x 10(6)/L and 90% of the cases had a CD(4)(+) T cell count less than 100 x 10(6)/L, 95% of the cases had a CD(4)(+)/CD(8)(+) ratio less than 0.20; (4) The most common abnormal chest radiological findings were bilateral diffuse interstitial infiltrations (19/22) and patchy shadows (14/22); (5) All patients were given trimethoprim-sulfamethoxazole (SMZco) and 86.4% of the patients were treated with corticosteroids concomitantly. Of the 22 PCP patients, 13 recovered, 5 gave up after knowing their definite diagnosis, 4 died. Comparing with the recovery patients, the 4 patients who died of PCP had much lesser CD(4)(+) T cell count (P = 0.07). CONCLUSIONS: Most PCP occurred in patients who were in their late stage of AIDS and with a CD(4)(+) T cell count below 100 x 10(6)/L. For these reasons, we suggest that whenever encountering a young patient presenting with fever, dyspnea, hypoxia, loss of weight, the possibility of PCP complicating AIDS should be considered, especially when chest radiological study revealed interstitial infiltration or patchy shadows. If HIV was confirmed to be positive, the combined therapy of SMZco and corticosteroids should be started immediately.

Mannan-modified adenovirus targeting TERT and VEGFR-2: A universal tumour vaccine.

Antigen-presenting cells including dendritic cells (DCs) express mannan receptors (MR) on their surface, which can be exploited in cancer therapy by designing immune-stimulatory viruses coated with mannan-modified capsids that then bind to DCs and initiate a potent immune response. Although the combination of anti-angiogenesis and cancer immunotherapy agents has a synergistic antitumor effect, more effective strategies for delivering such combinations are still required. Here we report the design and application of mannan-modified adenovirus that expresses both telomerase reverse transcriptase (TERT) and vascular endothelial growth factor receptor-2 (VEGFR-2). Cytotoxic T lymphocytes that are reactive to TERT and VEGFR-2 are capable of mounting an anti-tumour response in murine breast and colon tumour models and in a lung metastatic model. Compared with mannan-modified TERT adenovirus vaccine or mannan-modified VEGFR-2 adenovirus vaccine alone, the combined vaccine showed remarkably synergistic anti-tumour immunity in these models. Both TERT- and VEGFR-2-specific cytotoxic T lymphocytes (CTL) were identified in an in vitro cytotoxicity assay, and the CTL activity against tumour cells was significantly elevated in the combined vaccine group. Furthermore, CTL-mediated toxicity was blocked by anti-CD8 monoclonal antibodies. Thus, the combined mannan-modified TERT and VEGFR-2 adenovirus confers potent anti-tumour immunity by targeting both tumour cells and intratumoural angiogenesis.

The effect of chronic stress on anti-angiogenesis of sunitinib in colorectal cancer models.

Epidemiological and experimental evidence has shown that psychological stress can propel cancer progression. However, its role in anti-angiogenic therapy is not well understood. We previously found that exogenous norepinephrine attenuated the effect of sunitinib, a multi-targeted anti-angiogenic agent, in a mouse melanoma model. Here, we further evaluated the effects of chronic stress on sunitinib therapy in colorectal cancer models. We found that chronic restraint stress markedly weakened the efficacy of sunitinib, primarily through promoting the expression of vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) to stimulate tumor angiogenesis in vivo. This effect could be sufficiently mimicked by exogenous norepinephrine and blocked by the ß-antagonist propranolol. In vitro, norepinephrine up-regulated expression of VEGF and IL-8 in sunitinib-treated cancer cells mainly through the ß-adrenoceptor-cAMP-PKA signaling pathway. Norepinephrine also abrogated sunitinib-induced inhibition of cancer cell migration, but had no effect on direct anti-proliferative activity of sunitinib on cancer cells. These findings suggest that psychological stress might attenuate anti-angiogenic therapy primarily through activating beta-adrenergic signaling to promote tumor angiogenesis. It is also suggested that ß-blockers might improve anti-angiogenic outcome under psychological stress.

[A clinical review of 449 cases with fever of unknown origin].

OBJECTIVE: To investigate the causes of fever of unknown origin (FUO). METHODS: The clinical data were retrospectively analyzed from patients with FUO hospitalized in Peking Union Medical College Hospital from January 2000 to December 2003. During that period of time, 449 cases fulfilled the criteria of FUO. RESULTS: Out of the 449 FUO cases, definite diagnosis was eventually achieved in 387 patients (86.9%). The most common causes of FUO were infectious diseases (56.8%), with tuberculosis accounting for 43.6% of cases of infection. Seventy-six patients were suffered from collagen vascular diseases (CVD): with Still's disease, systemic lupus erythematosus and vasculitis accounting for 34.2% (26/76), 18.4% (14/76) and 13.2% (10/76) of the this category, respectively. 16.5% (64/449) of the FUO cases were diagnosed as malignancy. Miscellaneous causes were found in 7.0% of the FUO cases. However, no definite diagnosis had been made in the remaining 62 (13.8%) cases until they discharged from the hospital. CONCLUSIONS: In most FUO cases the causes can be diagnosed eventually after careful analysis of clinical data. While infectious diseases, especially tuberculosis, were still the most common causes of FUO, CVD and malignancy were also major causes of FUO and the incidence of malignancy were increased with the time.

[Dynamic changes of plasma cytokine levels in patients with severe acute respiratory syndrome].

OBJECTIVE: To elucidate the mechanism of strong inflammatory response in severe acute respiratory syndrome (SARS) patients. METHODS: 24 patients managed with a standard corticosteroid protocol developed by Peking Union Medical College Hospital were followed up for 2 months and their clinical outcomes were documented. Plasma levels of interleukin (IL)-1 beta, IL-2, IL-4, IL-8, IL-10, IL-12 p70, interferon gamma (IFN gamma), and tumor necrosis factor alpha (TNF alpha) were determined by quantitative ELISA during the course of disease respectively. 12 healthy blood donors were used as normal controls. RESULTS: All SARS patients had remarkably increased plasma IL-8 concentrations (median 31.23 ng/L) at the onset of disease compared with those of normal controls (6.28 ng/L, P < 0.01). Along with the course of disease IL-8 concentration kept going up and 75% (18/24) patients reached a peak median concentration of 149.65 ng/L (P < 0.01) at the third and fourth weeks. IL-8 came back to normal control levels one month after discharged from hospital. Meanwhile, SARS patients also showed high a TNF alpha level (median 23.12 ng/L) (P < 0.01) at the second week and reached a peak median of 136.35 ng/L (P < 0.05) at the third an fourth weeks. One month after discharged from hospital the plasma TNF alpha concentration fell down to a median of 94.88 ng/L, but it was still much higher than normal controls (3.77 ng/L, P < 0.01). CONCLUSION: The SARS-associated coronovirus infection may cause complex cytokine cascade. IL-8 and TNF alpha probably play important roles in mediating strong inflammatory response, which are thought to be responsible for lung injury in SARS patients.

[Clinical features and therapy of 106 cases of severe acute respiratory syndrome].

OBJECTIVE: To investigate the clinical characteristics of severe acute respiratory syndrome (SARS) and find out its effective treatment. METHODS: A total of 106 cases of SARS were analyzed prospectively. RESULTS: In this group, 56 were male and 50 female, aged from 15 to 81 years [average (36 +/- 10) years]. Common symptoms included fever (98.1%), chills (75.5%), cough (71.7%), headache and breathless (both 43.4%), diarrhea (24.5%) and rare rales in the lungs (11.2%). Laboratory test showed leukopenia (34.0%), lymphopenia (81.1%) and an extraordinary decrease of CD(4)(+) T cells (98.1%). Other rare abnormalities included liver injury (elevated alanine aminotransferase in 7.6%) and thrombocytopenia (3.8%). Almost all patients suffered from hypoxemia (PaO(2) less than 90 mm Hg in 90.2%, less than 70 mm Hg in 28.6%). Chest radiographs showed that unilateral focal patchy involvement in 34.0% of the patients, and unilateral multifocal or bilateral involvement were 11.3% and 46.2% respectively. Treatment regimens included small doses of steroids (methylprednisolone 40-80 mg, q12 h recommended) accompanied with broad-spectrum antibiotics such as the second generation of cephalosporins and macrolides and some other antiviral drugs. Meanwhile, emphasis was placed on oxygen support and coping with their underlying diseases. CONCLUSIONS: SARS has various presentations of clinical features and laboratory tests. Detection of CD(4)(+) T cell count is beneficial to diagnose SARS in early stage. Effective treatment includes various regimens, oxygen support and small doses of steroids.

[Dynamics of T lymphocyte subsets in SARS patients].

OBJECTIVE: To study dynamics of T lymphocyte subsets in severe acute respiratory syndrome (SARS). METHODS: Sequential anti-coagulated blood samples were collected from 46 cases of SARS patients during the 1st week, the 2nd week, the 3rd-5th week and the 8th-12th week after the infection. T lymphocyte subsets including CD3+CD4+ cells, CD3+CD8+ cells, naive CD4+ cells (CD4+CD45RA+CD62L+) and activated CD8+ cells (CD8+CD38+) were detected by 3-color flow cytometry. Fifty-six normal healthy blood donors were also detected as normal controls. RESULTS: Compared with the results of normal controls, both of the percentages of CD4+ cells and CD8+ cells of SARS patients were in normal levels during the 1st week, but the cell counts decreased significantly to (306 +/- 140)/mm3 and (270 +/- 143)/mm3, respectively. The cell count of naive CD4+ subset also remarkably decreased to (96 +/- 49)/mm3, and the percentage of CD8+CD38+ subset was higher than that of normal controls [(59.3 +/- 12.6)% vs (44.9 +/- 12.5)%]. During the 3rd-5th week, the CD8+ cell count and the percentage of CD8+CD38+ subset reached normal values, which were (581 +/- 356)/mm3 and (40.1 +/- 17.6)%, respectively. During the 8th-12th week, the cell counts of CD4+ cell [(578 +/- 193)/mm3] and naive CD4+ subset [(176 +/- 64)/mm3] were still less than those of normal controls, while compared with those of the 1st week, the increments were remarkable. CONCLUSIONS: T lymphocytes of SARS patients decreased dramatically but could be obviously resumed in a short time. It will take more than 8-12 weeks for CD4+ cell and naive CD4+ subset to reach to normal levels.

Exogenous norepinephrine attenuates the efficacy of sunitinib in a mouse cancer model.

BACKGROUND: Sunitinib alone exhibits satisfactory efficacy in several mouse homografts and xenografts but unsatisfactory efficacy in many kinds of solid tumors in clinic. Different from animals, receiving a diagnosis of cancer impacts chronic stress on patients. Here, we examine whether norepinephrine (NE), one of the most potent stress related hormones, leads to the difference in the efficacy of sunitinib between clinical and preclinical trials. METHODS: The influence of NE on mouse melanoma B16F1 cells under sunitinib was evaluated in vitro and in vivo. The ß-AR/cAMP/PKA (ß-adrenoceptor/cyclic adenosine monophosphate/protein kinase A) signaling pathway was also evaluated in human lung adenocarcinoma cells. RESULTS: We found that NE upregulated the expression of VEGF, IL-8 and IL-6 in vitro and stimulated tumor growth in vivo, which was mediated by ß-AR/cAMP/PKA signaling pathway and could be inhibited by propranolol, a ß-blocker for hypertension for decades. CONCLUSIONS: This research indicates exogenous norepinephrine attenuates the efficacy of sunitinib, and a combination of sunitinib and propranolol might be suggested as a new strategy in solid tumor in clinic.

Mannan-modified adenovirus encoding VEGFR-2 as a vaccine to induce anti-tumor immunity.

PURPOSE: Dendritic cell (DC) vaccines are a promising immunotherapeutic approach for treatment and prevention of cancer. While this methodology is widely accepted, it also has some limitations. Antigen-presenting cells including DCs express the mannan receptor (MR). The delivery of a mannan-modified tumor antigen to the MR has been demonstrated to be efficient. Vascular endothelial growth factor receptor-2 (VEGFR-2) is mainly responsible for angiogenesis and tumor growth. The goal of our study was to deliver VEGFR-2 to DCs by means of mannan-modified adenovirus. METHODS: VEGFR-2 recombinant adenovirus modified with oxidized mannan was constructed as a tumor vaccine to immunize mice in vivo. IFN-γ in mouse sera and spleen was detected by ELISA and ELISPOT. The killing activity of cytotoxic T lymphocyte (CTL) against VEGFR-2 was measured with a lactate dehydrogenase assay. Vessel densities in tumor tissues were detected by immunohistochemistry. Flow cytometry was used to test CD4(+) and CD8(+) T-cell counts in tumor tissues. RESULTS: The vaccine exhibited both protective and therapeutic efficacy in the inhibition of tumor growth and markedly prolonged survival in mice. Protection against metastasis was also observed. Furthermore, vaccination led to greater IFN-γ and VEGFR-2-specific CTLs. The specific immunity resulted in the suppression of angiogenesis and an increase in CD8(+) cells in tumor tissues. CONCLUSION: Oxidized mannan-modified adenovirus expressing VEGFR-2 could extraordinarily stimulate both protective and therapeutic immune response in a mice model. Our data suggest that the combination of cancer immunity and anti-angiogenesis via modified mannan is a promising strategy in tumor prophylaxis and therapy.