Bortezomib in combination with fludarabine plus cyclophosphamide for patients with relapsed or refractory mantle-cell lymphoma: results of the LYM-4003 study.

This study aimed to identify the maximum-tolerated dose (MTD) of cyclophosphamide when combined with bortezomib and fludarabine (B-FC) in a phase 1b trial, and to assess the efficacy and safety of this combination in a phase 2 trial in patients with relapsed or refractory MCL (rrMCL). Forty patients were enrolled between April 8, 2011, and October 10, 2015. The MTD of cyclophosphamide was identified to be 250 mg/m2 days 1-2. At a median follow-up of 31.6 months (13.5-47.4), among 32 patients in phase 2, 10 (31%) had a complete response and 13 (41%) had a partial response. The median progression-free survival was 21 months (95% CI 7.3-34.7), and the median overall survival was 32.4 months (95% CI 17.8-47.0). Grade 3-4 hematologic AEs included neutropenia (27%) and thrombocytopenia (39%). The B-FC regimen has satisfactory responses and manageable toxicities in rrMCL patients (ClinicalTrials.gov NCT01322776).

Increased autocrine interleukin-6 production is significantly associated with worse clinical outcome in patients with chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) remains incurable with current standard therapy. We have previously reported that an increased expression of interleukin-6 (IL-6) receptor CD126 leads to resistance of CLL cells to chemotherapy and worse prognosis for patients with CLL. In this study, we determine whether autocrine IL-6 production by CLL B cells is associated with poor clinical outcome and explore IL-6-mediated survival mechanism in primary CLL cells. Our results demonstrate that higher levels of autocrine IL-6 are significantly associated with shorter absolute lymphocyte doubling time, patients received treatment, without complete remission, advanced Binet stages, 17p/11q deletion, and shorter time to first time treatment and progression-free survival. IL-6 activated both STAT3 and nuclear factor kappa B (NF-κB) in primary CLL cells. Blocking IL-6 receptor and JAK2 inhibited IL-6-mediated activation of STAT3 and NF-κB. Our study demonstrates that an increased autocrine IL-6 production by CLL B-cells are associated with worse clinical outcome for patients with CLL. IL-6 promotes CLL cell survival by activating both STAT3 and NF-κB through diverse signaling cascades. Neutralizing IL-6 or blocking IL-6 receptor might contribute overcoming the resistance of CLL cells to chemotherapy. We propose that the measurement of autocrine IL-6 could be a useful approach to predict clinical outcome.

Vaccine-derived poliovirus surveillance in China during 2001-2013: the potential challenge for maintaining polio free status.

BACKGROUND: The goal of polio eradication is to complete elimination and containment of all wild, vaccine-related and Sabin polioviruses. Vaccine-derived poliovirus (VDPV) surveillance in China from 2001-2013 is summarized in this report, which has important implications for the global polio eradication initiative. METHODS: Acute flaccid paralysis (AFP) cases and their contacts with VDPVs isolated from fecal specimens were identified in our AFP surveillance system or by field investigation. Epidemiological and laboratory information for these children were analyzed and the reasons for the VDPV outbreak was explored. RESULTS: VDPVs were isolated from a total of 49 children in more than two-thirds of Chinese provinces from 2001-2013, including 15 VDPV cases, 15 non-polio AFP cases and 19 contacts of AFP cases or healthy subjects. A total of 3 circulating VDPVs (cVDPVs) outbreaks were reported in China, resulting in 6 cVDPVs cases who had not been vaccinated with oral attenuated poliomyelitis vaccine. Among the 4 immunodeficiency-associated VDPVs (iVDPVs) cases, the longest duration of virus excretion was about 20 months. In addition, one imported VDPV case from Myanmar was detected in Yunnan Province. CONCLUSIONS: Until all wild, vaccine-related and Sabin polioviruses are eradicated in the world, high quality routine immunization and sensitive AFP surveillance should be maintained, focusing efforts on underserved populations in high risk areas.

Identification and control of a poliomyelitis outbreak in Xinjiang, China.

BACKGROUND: The last case of infection with wild-type poliovirus indigenous to China was reported in 1994, and China was certified as a poliomyelitis-free region in 2000. In 2011, an outbreak of infection with imported wild-type poliovirus occurred in the province of Xinjiang. METHODS: We conducted an investigation to guide the response to the outbreak, performed sequence analysis of the poliovirus type 1 capsid protein VP1 to determine the source, and carried out serologic and coverage surveys to assess the risk of viral propagation. Surveillance for acute flaccid paralysis was intensified to enhance case ascertainment. RESULTS: Between July 3 and October 9, 2011, investigators identified 21 cases of infection with wild-type poliovirus and 23 clinically compatible cases in southern Xinjiang. Wild-type poliovirus type 1 was isolated from 14 of 673 contacts of patients with acute flaccid paralysis (2.1%) and from 13 of 491 healthy persons who were not in contact with affected persons (2.6%). Sequence analysis implicated an imported wild-type poliovirus that originated in Pakistan as the cause of the outbreak. A public health emergency was declared in Xinjiang after the outbreak was confirmed. Surveillance for acute flaccid paralysis was enhanced, with daily reporting from all public and private hospitals. Five rounds of vaccination with live, attenuated oral poliovirus vaccine (OPV) were conducted among children and adults, and 43 million doses of OPV were administered. Trivalent OPV was used in three rounds, and monovalent OPV type 1 was used in two rounds. The outbreak was stopped 1.5 months after laboratory confirmation of the index case. CONCLUSIONS: The 2011 outbreak in China showed that poliomyelitis-free countries remain at risk for outbreaks while the poliovirus circulates anywhere in the world. Global eradication of poliomyelitis will benefit all countries, even those that are currently free of poliomyelitis.

Safety of influenza A (H1N1) vaccine in postmarketing surveillance in China.

BACKGROUND: On September 21, 2009, China began administering vaccines, obtained from 10 different manufacturers, against 2009 pandemic influenza A (H1N1) virus infection in priority populations. We aimed to assess the safety of this vaccination program. METHODS: We designed a plan for passive surveillance for adverse events after immunization with the influenza A (H1N1) vaccine. Physicians or vaccination providers were required to report the numbers of vaccinees and all adverse events to their local Center for Disease Control and Prevention (CDC), which then reported the data to the Chinese CDC through the online National Immunization Information System's National Adverse Event Following Immunization Surveillance System. Data were collected through March 21, 2010, and were verified and analyzed by the Chinese CDC. RESULTS: A total of 89.6 million doses of vaccine were administered from September 21, 2009, through March 21, 2010, and 8067 vaccinees reported having an adverse event, for a rate of 90.0 per 1 million doses. The age-specific rates of adverse events ranged from 31.4 per 1 million doses among persons 60 years of age or older to 130.6 per 1 million doses among persons 9 years of age or younger, and the manufacturer-specific rates ranged from 4.6 to 185.4 per 1 million doses. A total of 6552 of the 8067 adverse events (81.2%; rate, 73.1 per 1 million doses) were verified as vaccine reactions; 1083 of the 8067 (13.4%; rate, 12.1 per 1 million doses) were rare and more serious (vs. common, minor events), most of which (1050) were allergic reactions. Eleven cases of the Guillain-Barré syndrome were reported, for a rate of 0.1 per 1 million doses, which is lower than the background rate in China. CONCLUSIONS: No pattern of adverse events that would be of concern was observed after the administration of influenza A (H1N1) vaccine, nor was there evidence of an increased risk of the Guillain-Barré syndrome.

PLCE1 rs2274223 polymorphism contributes to risk of esophageal cancer: evidence based on a meta-analysis.

We sought to reassess the association of PLCE1 rs2274223 and susceptibility to esophageal cancer (EC) through a meta-analysis of published case-control studies. Using the PubMed and Embase, we identified nine articles including fourteen case-control studies (15,225 cases and 23,620 controls). ORs and 95 % confidence intervals (CIs) of GG vs. AA, GG + GA vs. AA, GG vs. GA + AA, G vs. A, and AG vs. AA genetic models were estimated for each study. All of the genetic models indicated a statistically significant positive association with EC risk. The association appeared most pronounced for carriers of GG genotype (GG vs. AA: OR, 1.35; 95 % CI, 1.17 to 1.57), and weakest for individuals carrying GA genotype (GA vs. AA: OR, 1.13; 95 % CI, 1.05 to 1.23). Stratification analyses showed similar results in the population of Asians and in esophageal squamous cell carcinoma (ESCC). This meta-analysis provides strong statistical evidence for an elevated risk of EC associated with PLCE1 rs2274223. The association remains significant in Asian population and ESCC. Further investigations are warranted to validate these findings.

Enhanced surveillance of acute flaccid paralysis following importation of wild poliovirus in Xinjiang Uygur Autonomous Region, China.

BACKGROUND: After being polio free for more than 10 years, an outbreak occurred in China in 2011 in Xinjiang Uygur Autonomous Region (Xinjiang) following the importation of wild poliovirus (WPV) originating from neighboring Pakistan. METHODS: To strengthen acute flaccid paralysis (AFP) surveillance in Xinjiang, "zero case daily reporting" and retrospective searching of AFP cases were initiated after the confirmation of the WPV outbreak. To pinpoint all the polio cases in time, AFP surveillance system was expanded to include persons of all ages in the entire population in Xinjiang. RESULTS: Totally, 578 AFP cases were reported in 2011 in Xinjiang, including 21 WPV cases, 23 clinical compatible polio cases and 534 non-polio AFP cases. Of the 44 polio cases, 27 (61.4%) cases were reported among adults aged 15-53 years. Strengthening AFP surveillance resulted in an increase in the number of non-polio AFP cases in 2011 (148 children < 15 years) compared with 76 cases < 15 years in 2010. The AFP surveillance system in Xinjiang was sensitive enough to detect polio cases, with the AFP incidence of 3.28/100,000 among children < 15 years of age. CONCLUSIONS: Incorporating adult cases into the AFP surveillance system is of potential value to understand the overall characteristics of the epidemic and to guide emergency responses, especially in countries facing WPV outbreak following long-term polio free status. The AFP surveillance system in Xinjiang was satisfactory despite limitations in biological sample collection.

Pegylated filgrastim is comparable with filgrastim as support for commonly used chemotherapy regimens: a multicenter, randomized, crossover phase 3 study.

The purpose of this study was to compare the efficacy and safety of a single subcutaneous injection of pegylated filgrastim with daily filgrastim as a prophylaxis for neutropenia induced by commonly used chemotherapy regimens. Fifteen centers enrolled 337 chemotherapy-naive cancer patients with normal bone marrow function. All patients randomized into AOB and BOA arms received two cycles of chemotherapy. Patients received a single dose of pegylated filgrastim 100 µg/kg in cycle 1 (AOB) or cycle 2 (BOA) and daily doses of filgrastim 5 µg/kg/day in cycle 1 (BOA) or cycle 2 (AOB). Efficacy and safety parameters were recorded. The primary end point was the rate of protection against grade 4 neutropenia after chemotherapy [defined as the rate at which the absolute neutrophil count (ANC) remained >0.5×10(9)/l throughout the entire cycle]. Ninety-four percent of patients receiving pegylated filgrastim or filgrastim did not develop grade 4 neutropenia. The incidence of ANC<1.0×10(9)/l was 16.0% (50/313) after support with either pegylated filgrastim or filgrastim. The incidences of febrile neutropenia and antibiotic administration were similar in both groups. Notably, faster ANC recovery was observed with pegylated filgrastim support. The ANC nadir was also earlier with pegylated filgrastim (day 7) support than with filgrastim support (day 9), although the depth of nadir was not significantly different. A single subcutaneous injection of pegylated filgrastim 100 µg/kg provided adequate and safe neutrophil support comparable with daily subcutaneous injections of unmodified filgrastim 5 µg/kg/day in patients receiving commonly used standard-dose mild-to-moderate myelosuppressive chemotherapy regimens.

[Expression and prognostic value of regulatory T cells and M2 macrophages in diffuse large B-cell lymphoma tissues].

OBJECTIVE: To explore the prognostic value of regulatory T cells (Tregs) and M2 macrophages in diffuse large B-cell lymphoma (DLBCL) tissues. METHODS: The expression of CD163 and Foxp3 was detected by immunohistochemistry in 92 cases of DLBCL, and it was statistically analyzed whether their expressions correlate with clinical data and prognosis in patients with DLBCL. RESULTS: The density of M2 macrophage and regulatory T cells in DLBCL tumor tissues was significantly higher than that in the adjacent tissues (P = 0.02, P = 0.04). The expression of M2 macrophages was significantly positively correlated with regulatory T cells expression (r = 2.012, P < 0.05). High density of M2 or Tregs had a relationship with extranodal involvement (P < 0.05). Cox regression analysis showed that the expressions of CD163 and Foxp3 were independent prognostic factors of DLBCL (P < 0.05). CONCLUSIONS: Combined detection of the expression of CD163 and Foxp3 proteins and then evaluation of the amount of M2 macrophages and Tregs can be used to more closely predict the prognosis for DLBCL patients.

[Analysis on reported data of immunization monitoring system for category II vaccine in China, 2012].

OBJECTIVE: To analyze the immunization status of category II vaccine in Chinese Mainland in 2012. METHODS: The completeness of report unit by township and county, including 31 provinces (cities, municipalities) and Xinjiang Production and Construction Corps, the number of doses and the number of counties covered for category II vaccine at different areas, average types of category II vaccine by county were analyzed by descriptive epidemiological methods, according to monthly report of vaccination data for category II vaccines by township in 2012 which all of provinces and population were almost covered, through the National Immunization Program(NIP) monitoring information system of China. RESULTS: A total of 29 kinds of category II vaccine with 90 843 530 doses were reported in 2012, and the total average dose was 674.2 per 10 000 people. The report completeness by county and township were 83.32% (29 557/35 472) and 80.01% (396 652/495 756) respectively. The reported doses of rabies vaccine for human use, Haemophilus influenza type b vaccine and influenza vaccine was the top third vaccine, among those for all kinds of category II vaccine, which were 17 027 259, 13 996 206, 11 324 518 respectively, and 126.4, 103.9, 84.1 doses per 10 000 people. In 2773 county units, varicella attenuated live vaccine, influenza vaccine, rabies vaccine for human use were the top three kinds of category II vaccine in terms of the number of county where vaccines have been used in 2012, which were 2442(88.06%), 2415(87.09%), 2366(85.32%) respectively. Guangdong province with 12 266 531 doses was the highest report doses for category II vaccine whereas Qinghai province with 57 767 doses was the lowest number in 2012. Regarding to the average report doses by province, the highest or lowest number was 2425.0 doses per 10 000 people in Shanghai province, and 101.7 doses per 10 000 people in Qinghai province separately. CONCLUSION: Many kinds of category II vaccine with a large amount have been used in China, and there are significant different among areas. Surveillance and management for category II vaccines should be future improved.

Clinical Characteristics and Treatment of Early and Delayed Intra-Ccranial Infection After Ventriculoperitoneal Shunt in Adults: Retrospective Analysis of Nineteen Cases.

Objectives: Intra-cranial infection is the most serious complication after ventriculoperitoneal shunt (VPS). There were differences in clinical characteristics between early (occurs within one month after VPS, the early group) and delayed (occurs 1 month or more after VPS, the delayed group) infections. The aim of this study is to clarify the differences between the two groups. Patients and Methods: All cases diagnosed as intracranial infection after VPS between September 2017 and December 2021 were collected. Clinical data were reviewed and analyzed retrospectively. Results: Nineteen cases met the inclusion criteria, including 12 cases in the early group and seven cases in the delayed group. There were no significant differences between the two groups in gender, age, and etiology of hydrocephalus. Cases in the early group usually had fever with worsening consciousness (11; 91.7%), which was caused by surgical operations (10; 83.3%) with gram-positive coccis infection (9; 75.0%), whereas those in the delayed group had abdominal pain (5; 71.4%), caused by abdominal factor (7; 100%) with gram-negative bacilli infection (6; 85.7%). There were differences in symptoms (p < 0.01), causes of infection (p < 0.001), and pathogens (p < 0.05). Shunt removal was performed for all 19 cases. After the infection was controlled, eight cases received VPS again, and no re-infection occurred after a follow-up of four to 22 months. Conclusions: It is suggested in this study that there were differences between the two groups in terms of etiology, symptoms, and pathogens. The results can provide theoretical basis for prevention, early diagnosis, and reasonable treatment of infection after VPS.

A novel influenza A (H1N1) vaccine in various age groups.

BACKGROUND: There is an urgent need for a vaccine that is effective against the 2009 pandemic influenza A (H1N1) virus. METHODS: A split-virus, inactivated candidate vaccine against the 2009 H1N1 virus was manufactured, and we evaluated its safety and immunogenicity in a randomized clinical trial. Subjects were between 3 and 77 years of age, stratified into four age groups. The immunization schedule consisted of two vaccinations, 21 days apart. Subjects were injected with placebo or with vaccine, with or without alum adjuvant, at doses of 7.5 microg, 15 microg, or 30 microg. Serologic analysis was performed at baseline and on days 21 and 35. RESULTS: A total of 2200 subjects received one dose, and 2103 (95.6%) received the second dose, of vaccine or placebo. No severe adverse side effects associated with the vaccine were noted. In the nonadjuvanted-vaccine groups, injection-site or systemic reactions, most mild in nature, were noted in 5.5 to 15.9% of subjects. Among the subjects receiving 15 microg of nonadjuvanted vaccine, a hemagglutination-inhibition titer of 1:40 or more was achieved by day 21 in 74.5% of subjects between 3 and 11 years of age, 97.1% of subjects between 12 and 17 years, 97.1% of subjects between 18 and 60 years, and 79.1% of subjects 61 years of age or older; by day 35, the titer had been achieved in 98.1%, 100%, 97.1%, and 93.3% of subjects, respectively. The proportion with a titer of 1:40 or more was generally highest among the subjects receiving 30 microg of vaccine, with or without adjuvant. Vaccine without adjuvant was associated with fewer local reactions and greater immune responses than was vaccine with adjuvant. CONCLUSIONS: These data suggest that a single dose of 15 microg of hemagglutinin antigen without alum adjuvant induces a typically protective immune response in the majority of subjects between 12 and 60 years of age. Lesser immune responses were seen after a single dose of vaccine in younger and older subjects. (ClinicalTrials.gov number, NCT00975572).

Frizzled-8 as a putative therapeutic target in human lung cancer.

Lung cancer is the leading cause of cancer related deaths worldwide. It is necessary to better understand the molecular mechanisms involved in lung cancer in order to develop more effective therapeutics for the treatment of this disease. Recent reports have shown that Wnt signaling pathway is important in a number of cancer types including lung cancer. However, the role of Frizzled-8 (Fzd-8), one of the Frizzled family of receptors for the Wnt ligands, in lung cancer still remains to be elucidated. Here in this study we showed that Fzd-8 was over-expressed in human lung cancer tissue samples and cell lines. To investigate the functional importance of the Fzd-8 over-expression in lung cancer, we used shRNA to knock down Fzd-8 mRNA in lung cancer cells expressing the gene. We observed that Fzd-8 shRNA inhibited cell proliferation along with decreased activity of Wnt pathway in vitro, and also significantly suppressed A549 xenograft model in vivo (p<0.05). Furthermore, we found that knocking down Fzd-8 by shRNA sensitized the lung cancer cells to chemotherapy Taxotere. These data suggest that Fzd-8 is a putative therapeutic target for human lung cancer and over-expression of Fzd-8 may be important for aberrant Wnt activation in lung cancer.

Pharmacokinetic characteristics of vincristine sulfate liposomes in patients with advanced solid tumors.

AIM: To evaluate the single- and multiple-dose pharmacokinetics of vincristine sulfate liposomes (VSLI) in patients with advanced solid tumors. METHODS: In single-dose pharmacokinetic study, 16 patients were administered VSLI (1.5, 2.0, or 2.3 mg·m(-2)) through intravenous infusion. Another 6 patients receiving vincristine sulfate (VCR, 2.0 mg) were taken as the control. In multiple-dose pharmacokinetic study, 12 patients were administered VSLI (1.5 or 1.8 mg·m(-2)) through intravenous infusion weekly for 4 consecutive weeks. The plasma concentration of VSLI was determined using the liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. RESULTS: After intravenous infusion of the single dose of VSLI, the plasma concentrations were characterized by bi-exponential decline curves. No statistically significant differences were observed between the main pharmacokinetic parameters in the 3 dose groups. Compared with the patients receiving VCR, the patients treated with VSLI displayed an increase in the area under the plasma concentration vs time curve (AUC), and a decrease in plasma clearance rates. On the 4th cycle in the multiple-dose study, the plasma concentration of VCR in all subjects prior to the weekly administration was below the lower limit of quantification (LLOQ). The calculated pharmacokinetic parameters from the subjects in the multiple- and single-dose (1.5 mg·m(-2)) groups had no significant differences. Although the administration of liposomal VCR may significantly elevate the plasma concentration of VCR, VSLI-associated adverse events were similar to those associated with conventional VCR. CONCLUSION: VSLI exhibits a lower clearance and a higher AUC compared with conventional VCR. No accumulation was observed in patients exposed to VSLI for 4 consecutive weeks. VSLI was generally tolerated in the subjects. The phase II dose of VSLI may be recommended as 4 doses of 1.5 mg·m(-2) for treatment of patients with advanced solid tumors.

[Efficacy and adverse effets of nimotuzumab plus palitaxel liposome and carboplatin in the treatment for advanced non-small cell lung cancer].

OBJECTIVE: To evaluate the efficacy of nimotuzumab combined with palitaxel liposome and carboplatin (LP) regimen for treatment of advanced non-small cell lung cancer (NSCLC), and to observe the changes of tumor markers and toxicities in the treatment. METHODS Forty-one patients with advanced NSCLC were randomly divided into 2 groups: 21 patients in the observation group were treated with nimotuzumab (200 mg per week for 6 weeks), palitaxel liposome 160 mg/m2 and carboplatin (AUC = 6). 20 patients in the control group were given LP regimen. Each group completed two cycles of chemotherapy. The level of tumor markers (CEA, CYFR21-1 and NSE) and toxicities were checked at one week before and after the treatment. Thoracic CT examinations were taken before treatment and at the fourth week and eighth week after treatment. RESULTS: In the observation group, there were 2 cases of CR, 7 cases of PR, 9 cases of SD and 3 cases of PD. The objective response rate (RR) was 42. 9% in the observation group. In the control group, there were 1 case of CR, 6 cases of PR, 8 cases of SD and 5 cases of PD, with a RR of 35.0% in this group. There was no significant difference in the RR between the two groups (P = 0.751). The time to progression (TIP) was 6. 9 months in the observation group and 5. 7 months in the control group, with a significant difference (P = 0.027). The levels of NSE decreased significantly in both groups and showed a significant difference (P = 0.039). The levels of CEA and CYFRA21 in both groups were decreased after treatment, but did not show a significant difference before and after treatment, respectively. Except 3 cases had I-II skin toxicities on the faces in the observation group, there was no significant difference in toxicities between the two groups. CONCLUSION: Nimotuzmab combined with LP regimen shows a synergistic effect, can increase the efficacy and prolong TFP in advanced NSCLC patients. The toxicities are mild and tolerable.

[Efficacy and survival status of retuximab-NCE regimen treatment in patients with relapsed or refractory B cell non-Hodgkin's lymphoma].

OBJECTIVE: The aim of this study was to analyze the efficacy and toxicity of RNCE regimen in the treatment of relapsed or refractory B cell non-Hodgkin's lymphoma (NHL). METHODS: From January 2000 to December 2005, 46 patients with relapsed or refractory B cell NHL were treated by RNCE regimen with or without radiotherapy for the involved field. The clinical characteristics, response, toxicity and long-term survival results were analyzed retrospectively. RESULTS: A total of 46 patients were eligible. The complete response rate of second-line therapy was 52.17% (24/46), and the overall response rate was 82.61% (38/46). The median follow-up duration in this series was 69 months (range:6 to 102 months). The overall 1, 3, 5-year survival rate was 74.8%, 48.3%, 40.1%, respectively, with a median survival time of 30.2 months (5 to 65 months), and median progression free survival time of 10.9 months (2 to 31 months). The major toxicities were myelosuppression, GI toxicity, fatigue, fever and alopecia. CONCLUSION: Our data show that RNCE regimen treatment is effective and well tolerated in patients with relapsed or refractory B cell non-Hodgkin's lymphoma.

[Epigenetics in tumorigenesis: advances and clinical implications].

Cancer is a leading cause of death worldwide and the total number of cases globally keeps increasing. For many years, cancer has been thought to be caused by a series of DNA sequence alterations and thus is thought to be a "genetic" disease. However, studies in the last decade, including the large-scale cancer genomics projects, have highlighted the rising importance of epigenetic regulation in cancer. Here, we review recent advances in understanding how chromatin-based epigenetic regulation participates in tumorigenesis and discuss the growing implications of these advances for developing novel strategies to prevent, diagnose, as well as treat cancer.

Safety and immunogenicity of 2009 pandemic influenza A H1N1 vaccines in China: a multicentre, double-blind, randomised, placebo-controlled trial.

BACKGROUND: The current influenza pandemic calls for a safe and effective vaccine. We assessed the safety and immunogenicity of eight formulations of 2009 pandemic influenza A H1N1 vaccine produced by ten Chinese manufacturers. METHODS: In this multicentre, double-blind, randomised trial, 12 691 people aged 3 years or older were recruited in ten centres in China. In each centre, participants were stratified by age and randomly assigned by a random number table to receive one of several vaccine formulations or placebo. The study assessed eight formulations: split-virion formulation containing 7.5 microg, 15 microg, or 30 microg haemagglutinin per dose, with or without aluminium hydroxide adjuvant, and whole-virion formulation containing 5 microg or 10 microg haemagglutinin per dose, with adjuvant. All formulations were produced from the reassortant strain X-179A (A/California/07/2009-A/PR/8/34). We analysed the safety (adverse events), immunogenicity (geometric mean titre [GMT] of haemagglutination inhibition antibody), and seroprotection (GMT >or=1:40) of the formulations. Analysis was by per protocol. Two sites registered their trial with ClinicalTrials.gov, numbers NCT00956111 and NCT00975572. The other eight studies were registered with the State Food and Drug Administration of China. FINDINGS: 12 691 participants received the first dose on day 0, and 12 348 participants received the second dose on day 21. The seroprotection rate 21 days after the first dose of vaccine ranged from 69.5% (95% CI 65.9-72.8) for the 7.5 microg adjuvant split-virion formulation to 92.8% (91.9-93.6) for the 30 microg non-adjuvant split-virion formulation. The seroprotection rate was 86.5% (796 of 920; 84.1-88.7) in recipients of one dose of the 7.5 microg non-adjuvant split-virion vaccine compared with 9.8% (140 of 1432; 8.3-11.4) in recipients of placebo (p<0.0001). One dose of the 7.5 microg non-adjuvant split-virion vaccine induced seroprotection in 178 of 232 children (aged 3 years to <12 years; 76.7%, 70.7-82.0), 211 of 218 adolescents (12 years to <18 years; 96.8%, 93.5-98.7), 289 of 323 adults (18-60 years; 89.5%, 85.6-92.6), and 118 of 147 adults older than 60 years (80.3%, 72.9-86.4), meeting the European Union's licensure criteria for seroprotection in all age-groups. In children, a second dose of the 7.5 microg formulation increased the seroprotection rate to 97.7% (215 of 220, 94.8-99.3). Adverse reactions were mostly mild or moderate, and self-limited. Severe adverse effects occurred in 69 (0.6%, 0.5-0.8) recipients of vaccine compared with one recipient (0.1%, 0-0.2) of placebo. The most common severe adverse reaction was fever, which occurred in 25 (0.22%; 0.14-0.33) recipients of vaccine after the first dose and four (0.04%; 0.01-0.09) recipients of vaccine after the second dose compared with no recipients of placebo after either dose. INTERPRETATION: One dose of non-adjuvant split-virion vaccine containing 7.5 microg haemagglutinin could be promoted as the formulation of choice against 2009 pandemic influenza A H1N1 for people aged 12 years or older. In children (aged <12 years), two 7.5 mug doses might be needed. FUNDING: Sinovac Biotech, Hualan Biological Bacterin, China National Biotec Group, Beijing Tiantan Biological Products, Changchun Institute of Biological Products, Changchun Changsheng Life Sciences, Jiangsu Yanshen Biological Technology Stock, Zhejiang Tianyuan Bio-Pharmaceutical, Lanzhou Institute of Biological Products, Shanghai Institute of Biological Products, and Dalian Aleph Biomedical.

Effect of aluminum hydroxide adjuvant on the immunogenicity of the 2009 pandemic influenza A/H1N1 vaccine: multi-level modeling of data with repeated measures.

OBJECTIVE: To evaluate the effect of the aluminum hydroxide (Al-OH) adjuvant on the 2009 pandemic influenza A/H1N1 (pH1N1) vaccine. METHODS: In a multicenter, double-blind, randomized, placebo-controlled trial, participants received two doses of split-virion formulation containing 15 µg hemagglutinin antigen, with or without aluminum hydroxide (Al-OH). We classified the participants into six age categories (>61 years, 41-60 years, 19-40 years, 13-18 years, 8-12 years, and 3-7 years) and obtained four blood samples from each participant on days 0, 21, 35, and 42 following the first dose of immunization. We assessed vaccine immunogenicity by measuring the geometric mean titer (GMT) of hemagglutination inhibiting antibody. We used a two-level model to evaluate the fixed effect of aluminum Al-OH and other factors, accounting for repeated measures. RESULTS: The predictions of repeated measurement on GMTs of formulations with or without Al-OH, were 80.35 and 112.72, respectively. Al-OH significantly reduced immunogenicity after controlling for time post immunization, age-group and gender. CONCLUSION: The Al-OH adjuvant does not increase but actually reduces the immunogenicity of the split-virion pH1N1 vaccine.

[Nimotuzumab in combination with chemotherapy in patients with advanced non-small cell lung cancer].

OBJECTIVE: To evaluate the role of nimotuzumab in combination with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). METHODS: The clinical data of 37 NSCLC patients who received nimotuzumab in combination with chemotherapy in Tianjin Medical University Cancer Hospital from January 2009 to October 2010 were retrospectively reviewed. Of the thirty-seven patients, 12 patients were in stage III B, 25 patients in stage IV. Twenty-four patients recived platinum-based chemotherapy in combination with nimotuzumab, 13 patients recived nonplatinum-based chemotherapy in combination with nimotuzumab. Ten patients received nimotuzumab in combination with chemotherapy as first-line regimen, 23 patients as second-line regimen, 4 patients as third-line regimen. RESULTS: Of the 37 advanced NSCLC patients who received nimotuzumab in combination with chemotherapy, the total number of chemotherapy were 137 cycles, the mean number was 3.7 cycles. One patient had complete remission (CR), 9 patients had partial remission (PR), 16 cases had stable disease (SD), and 11 patients had progressive disease (PD). The response rate (RR) was 27% and clinical benefit rate (CBR) was 70.3%. The main side effects were bone marrow suppression and gastrointestinal reactions. Grade I acneiform rash was found in one patient. CONCLUSION: The regimen of nimotuzumab in combination with chemotherapy can improve the response rate and was well tolerated in patients with advanced non-small cell lung cancer.