Hepatocellular carcinoma (HCC) is highly malignant and prone to multicentric occurrence. Differentiation between a true relapse of HCC and a second primary tumour appearing is of clinical importance. At this point, no convenient method is available to determine the origin of these HCCs. Tissue samples were obtained from 19 patients and analysed for the promoter hypermethylation status of multiple tumour suppressor genes (p16, DAP-Kinase, MGMT, GSTP1, APC, RIZ1, SFRP1, SFRP2, SFRP5, RUNX3, and SOCS1) using methylation-specific PCR (MSP). Methylation status was used to determine tumour clonality. In each of the 19 cases, at least one tumour was recognised as having an aberrantly methylated gene. The frequency of the methylation in tumour tissue was 57.1% in p16, 2.4% in DAP-kinase, 23.8% in GSTP1, 90.5% in APC, 45.2% in RIZ1, 64.3% in SFRP1, 59.5% in SFRP2, 28.6% in SFRP5, 47.6% in RUNX3, and 54.8% in SOCS1, while in MGMT, no aberrant methylation was detected. The methylation status of these genes was assessed using MSP as being either positive or negative, and was used to determine the tumour clonality. The clonality of every tumour could be decided even with lesions that could not be judged by clinical diagnosis or by another molecular method (mt DNA mutation). Determining the methylation status of multiple genes in multicentric HCC was useful as a clonal marker and provided useful information for characterising the tumour. From our findings, multicentric HCCs tend to occur more independently than metastatically from the original tumour. Expanded study should be pursued further for a better understanding of the molecular mechanism of hepatocarcinogenesis.

IntroductionInadequate knowledge, negative attitudes and risky practices are major hindrances to preventing the spread of HIV. This study aimed to assess HIV-related knowledge, attitudes and practices (KAPs) of high school students in Lao People's Democratic Republic (PDR).MethodsA cross-sectional study on unmarried male students aged between 16 and 19 years old was undertaken in 2010 to evaluate their KAPs. We selected 300 eligible grade VII students through systematic random sampling from different high schools in one province of Lao PDR.ResultsThe majority of students surveyed were aware that HIV can be transmitted by sexual intercourse (97.7%), from mother to child (88.3%) and through sharing needles or syringes (92.0%). Misconceptions about transmission of HIV were observed among 59.3% to 74.3% of respondents. Positive attitudes towards HIV/AIDS were observed among 55.7% of respondents. Nearly half of the surveyed students (45.3%) said that they would be willing to continue studying in a school with HIV-positive friends, and 124 (41.3%) said they would continue attending a school with HIV-positive teachers. Ninety-four (31.3%) students had a history of sexual intercourse, and 70.2% of these students had used a condom. However, only 43.9% said they used condoms consistently. Students with medium and high levels of knowledge were 4.3 (95% CI=2.1–9.0, P<0.001) and 13.3 (95% CI=6.5–27.4, P<0.001) times more likely to display positive attitudes towards people living with HIV. Similarly, safe practices related to safe sex were also observed among students with medium (OR=2.8, 95% CI=0.9–8.8, P=0.069) and high levels of knowledge (OR=1.9, 95% CI=0.6–6.2, P=0.284). More than three-quarters of students mentioned television and radio as major sources of information on HIV/AIDS.ConclusionsDespite adequate knowledge about HIV/AIDS among the school students, misconceptions about routes of transmission were found. Negative attitudes to HIV/AIDS and risky practices were also present. Educational programmes with specific interventions are recommended to increase KAPs and to prevent new HIV infections among students in Lao PDR.

Oncolytic viral therapy has been accepted as a standard immunotherapy since talimogene laherparepvec (T-VEC, Imlygic®) was approved by the Food and Drug Administration (FDA) and European Medicines Agency (EMA) for melanoma treatment in 2015. Various oncolytic viruses (OVs), such as HF10 (Canerpaturev—C-REV) and CVA21 (CAVATAK), are now actively being developed in phase II as monotherapies, or in combination with immune checkpoint inhibitors against melanoma. Moreover, in glioma, several OVs have clearly demonstrated both safety and a promising efficacy in the phase I clinical trials. Additionally, the safety of several OVs, such as pelareorep (Reolysin®), proved their safety and efficacy in combination with paclitaxel in breast cancer patients, but the outcomes of OVs as monotherapy against breast cancer have not provided a clear therapeutic strategy for OVs. The clinical trials of OVs against pancreatic cancer have not yet demonstrated efficacy as either monotherapy or as part of combination therapy. However, there are several oncolytic viruses that have successfully proved their efficacy in different preclinical models. In this review, we mainly focused on the oncolytic viruses that transitioned into clinical trials against melanoma, glioma, pancreatic, and breast cancers. Hence, we described the current status and future prospects of OVs clinical trials against melanoma, glioma, pancreatic, and breast cancers.

In order to evaluate noise components included in pathologic voice signals, a novel acoustic measure, normalized noise energy (NNE), is proposed and its effectiveness for the detection of laryngeal pathologies is investigated with 250 vowel samples spoken by 64 control (normal) subjects and 186 patients with various laryngeal diseases. The NNE is automatically computed from the voice signals using an adaptive comb filtering method performed in the frequency domain. Experiments with the voice samples show that the NNE is especially effective for detecting glottic cancer, recurrent nerve paralysis, and vocal cord nodules. Specifically, when glottic cancer is represented in terms of the T classification adopted by the UICC (Union Internationale Contre le Cancer), glottic T2-T4 cancer can be perfectly discriminated from normal samples, but 22.6% of patients with glottic T1 cancer are incorrectly classified as normal, with an error rate of 9.4% for normal subjects.

In 2005, we initiated a clinical trial that examined the efficacy of the oncolytic virus HF10 to treat pancreatic cancer. Pancreatic cancer continues to have a high mortality rate, despite multimodal treatments for patients, and new therapeutic methods are greatly needed. The current mainstream methods for cancer treatment include biological therapeutics such as trastuzumab (Herceptin) for breast cancer or erlotinib (Tarceva) for non-small cell lung cancer. Oncolytic virus therapy is a new and promising treatment strategy for cancer. Oncolytic viruses are novel biological therapeutics for advanced cancer that appear to have a wide spectrum of anticancer activity with minimal human toxicity. To examine the efficacy of oncolytic virus therapy for pancreatic cancer, we initiated pilot studies by injecting six patients with non-resectable pancreatic cancer with three doses of HF10. All patients were monitored for 30 days for local and systemic adverse effects and were not administered any other therapeutics during this period. There were no adverse side-effects, and we observed some therapeutic potential based on tumor marker levels, survival, pathological findings and diagnostic radiography. The tumors were classified as stable disease in three patients, partial response in one patient and progressive disease in two patients.