Female breast cancer patients have an increased risk of developing subsequent malignant diseases, but this issue is rarely discussed in regards to male breast cancer patients. Thus, we conducted a national survey that included 100,915 female and 578 male breast cancer patients to investigate the risk of second primary malignancy (SPM). During a follow-up period that included 529,782 person-years, 3,153 cases of SPM developed. Compared with the general population, the standardized incidence ratio (SIR) of SPM in breast cancer patients was 1.51 [95% confidence interval (CI): 1.46–1.56]. The observed risk was significantly higher in male patients (SIR 2.17, 95% CI 1.70–2.73) and in patients whose age at breast cancer diagnosis was 40 years or younger (SIR 3.39, 95% CI 2.80–4.07), comparing to age-matched general population. Compared with the overall female population, the SIRs of female breast cancer patients with uterine (SIR: 2.66, 95% CI: 2.37–2.98), thyroid (SIR: 2.30, 95% CI: 2.02–2.62), and bone and soft tissue (SIR: 2.16, 95% CI: 1.56–2.91) cancers were significantly increased. Male breast cancer patients also displayed significantly higher SIRs for thyroid (SIR: 13.2, 95% CI: 1.60–47.69), skin (SIR: 8.24, 95% CI: 3.02–17.94) and head and neck (SIR: 4.41, 95% CI: 2.35–7.54) cancers. Among breast cancer patients, risk factors significantly associated with SPM included male gender, older age, chemotherapy treatment and comorbidity with liver cirrhosis. From our analysis, we concluded that the risk of SPM was significantly higher for both male and female breast cancer patients compared with the general population, suggesting that more intensive surveillance may be needed, especially in high-risk patients.

Given the failures of nonreplicating vaccines against chronic hepatitis C virus (HCV) infection, we hypothesized that a replicating viral vector may provide protective immunity. Four chimpanzees were immunized transdermally twice with recombinant vaccinia viruses (rVV) expressing HCV genes. After challenge with 24 50% chimpanzee infective doses of homologous HCV, the two control animals that had received only the parental VV developed chronic HCV infection. All four immunized animals resolved HCV infection. The difference in the rate of chronicity between the immunized and the control animals was close to statistical significance (P ‫؍‬ 0.067). Immunized animals developed vigorous gamma interferon enzyme-linked immunospot responses and moderate proliferative responses. To investigate cross-genotype protection, the immunized recovered chimpanzees were challenged with a pool of six major HCV genotypes. During the acute phase after the multigenotype challenge, all animals had high-titer viremia in which genotype 4 dominated (87%), followed by genotype 5 (13%). However, after fluctuating low-level viremia, the viremia finally turned negative or persisted at very low levels. This study suggests the potential efficacy of replicating recombinant vaccinia virus-based immunization against chronic HCV infection.Nearly half a billion people, 1 in 12 of the world's population, are infected with hepatitis B or C viruses, resulting in about 1.5 million deaths each year (3). While hepatitis C virus (HCV) infection accounts for a heavy burden of chronic liver disease, cirrhosis, and hepatocellular carcinoma, vaccines are not yet available. A candidate HCV vaccine was developed by investigators at Chiron Corporation in 1994 (13). This vaccine, composed of recombinant HCV E1E2 proteins, produced in cell culture, protected a high proportion of chimpanzees against development of acute infection after challenge with small quantities of homologous genotype HCV; however, it failed to uniformly prevent chronic infections. Furthermore, it failed to protect against a heterologous subtype challenge (26). Immunity induced by this candidate vaccine appeared to depend on induction of an antibody response, which was extremely short lived (13), suggesting that immunity would be of limited duration. Puig et al. (50) also evaluated E1E2 protein immunization and found that this induced a delay in virus replication but did not prevent chronic infection.As it is now considered probable that cell-mediated immunity is necessary for the control of chronic HCV infection (52, 63), recent candidate HCV vaccines have been designed to induce cell-mediated immunity. These include vaccines using DNA-based immunization (21-23, 29, 30, 35-38, 68, 72), DNA priming followed by HCV protein boosting (53, 59, 70), DNA priming followed by recombinant avipoxvirus (43, 44), recombinant modified vaccinia virus (rVV) Ankara (54), or recombinant adenovirus boosting (40,46,69), recombinant adenovirus priming and DNA boosting (20), recombinant modified vaccinia virus Ankar...

A simple method, primer specific and mispair extension analysis (PSMEA) with pfu DNA polymerase was developed for genotyping. PSMEA is based on the unique properties of 3'-->5' exonuclease proofreading activity. In the presence of an incomplete set of dNTPs, pfu was found to be extremely discriminative in nucleotide incorporation and proofreading at the initiation step of DNA synthesis, completely preventing primer extension when mispair(s) are found adjacent to the 3'-end of the primer. This has allowed us to accurately detect nucleotide variations, deletions and insertions for fast genotyping.

To evaluate the risk of secondary primary malignancy (SPM) in patients with cervical cancer using a nationwide population-based dataset.Patients newly diagnosed with cervical cancer between 1997 and 2011 were identified using Taiwan's National Health Insurance database. Patients with antecedent malignancies were excluded. Standardized incidence ratios (SIRs) for SPM were calculated by comparing with the cancer incidence in the general population. Risk factors for cancer development were analyzed using Cox proportional hazard models.During the 14-year study period (follow-up of 223,062 person-years), 2004 cancers developed in 35,175 patients with cervical cancer. The SIR for all cancers was 1.56 (95% confidence interval, 1.50–1.63, P < 0.001). SIRs for follow-up periods of >10, 5 to 10, 1 to 5, and <1 year were 1.37, 1.51, 1.34, and 2.59, respectively. After the exclusion of SPM occurring within 1 year of cervical cancer diagnosis, SIRs were significantly higher for cancers of the esophagus (2.05), stomach (1.38), colon, rectum, and anus (1.36); lung and mediastinum (2.28), bone and soft tissue (2.23), uterus (3.76), bladder (2.26), and kidneys (1.41). Multivariate analysis showed that age ≥60 was a significant SPM risk factor (hazard ratio [HR] 1.59). Different treatments for cervical cancer, including radiotherapy (HR 1.41) and chemotherapy (HR 1.27), had different impacts on SPM risk. Carboplatin and fluorouracil independently increased SPM risk in cervical cancer patients.Patients with cervical cancer are at increased risk of SPM development. Age ≥60 years, chemotherapy, and radiotherapy are independent risk factors. Carboplatin and fluorouracil also increased SPM risk independently. Close surveillance of patients at high risk should be considered for the early detection of SPMs.