Paclitaxel-Containing Extract Exerts Anti-Cancer Activity through Oral Administration in A549-Xenografted BALB/C Nude Mice: Synergistic Effect between Paclitaxel and Flavonoids or Lignoids.

Taxus yunnanensis is a paclitaxel-containing herb with traditional usage in cancer treatment, and its extract possesses great oral bioavailability of paclitaxel. However, it is elusive whether paclitaxel-containing extract (HDS-1) can exert anti-tumor effect through oral administration and how other components contribute to its efficacy. Therefore, we investigate the oral-route anti-tumor effect of HDS-1 in A549-bearing mice. HDS-1-derived flavonoids (HDS-2) and lignoids (HDS-3) are hypothesized to contribute to HDS-1's efficacy, and their effects of enhancing enterocytic absorption and cytotoxicity of paclitaxel are validated in 2 permeability experiments and apoptosis-related assay, respectively. In vivo, A549 growth is significantly inhibited by 86.1 ± 12.94% (P < 0.01) at 600 mg/kg of HDS-1 and 65.7 ± 38.71% (P < 0.01) at 200 mg/kg. HDS-2 and HDS-3 significantly reduce the efflux ratio of paclitaxel to 2.33 and 3.70, respectively, in Caco-2 permeability experiment and reduce paclitaxel reflux in MDCK-MDR1 experiment. Furthermore, HDS-2 and HDS-3 potentiated paclitaxel-induced cytotoxicity by 19.1-22.45% (P < 0.05) and 10.52-18.03% (P < 0.05), respectively, inhibited the expression of cyclinB1, Bcl-2, and pMCL-1, and increased the percentage of necrosis cell in the condition of paclitaxel exposure. Conclusively, paclitaxel-containing extracts exert anti-cancer effects through oral administration, and flavonoid and lignoids contribute to its anti-cancer effect through simultaneously improving enterocytic absorption of paclitaxel and the cytotoxic effect of paclitaxel.

Persistence and clearance of oral human papillomavirus infections: A prospective population-based cohort study.

OBJECTIVE: This study aimed to evaluate the incidence of and factors associated with persistence and clearance of oral human papillomavirus (HPV) infections. METHOD: A prospective cohort study invited 458 subjects (231 HPV-positive and 227 HPV-negative at baseline) to attend follow-ups at 12 months. Those 231 HPV-positive subjects and 10 new infections were invited to reassessment at 24 months. We used next-gen sequencing for detection and genotyping of HPV. RESULTS: α-HPV infections showed higher persistence rates than ß/γ-HPV (22.7% vs 9.2% at 12 months [P < .05], 10.6% vs 6.8% at 24 months [P = .30]). Clearance rates of α-HPV were lower than ß/γ-HPV at 12 months (31.8% vs 45.1%; P = .05) and higher at 24 months (7.6% vs 4.8%; P = .36). Persistence of ß/γ-HPV was positively associated with males (crude odds ratio [COR] = 3.8, 95% confidence interval [CI] = 1.3-11.2), elderly (51-65 vs 16-50 years; COR = 5.1, 95% CI = 1.2-22.3), and smoking (COR = 4.3, 95% CI = 1.9-9.6). Drinking (COR = 0.5, 95% CI = 0.3-0.9), handwashing less than 90% of times before meals (COR = 0.6, 95% CI = 0.3-0.9), and using public bath more than once per month (COR = 0.5, 95% CI = 0.2-0.9) were risk factors hindering ß/γ-HPV clearance. CONCLUSIONS: This study identified factors associated with persistence and clearance of oral HPV infections among Chinese. Studies on other ethnogeographic groups may further inform prevention strategies of oral HPV infection and immunization programmes.

Prevalence and Epidemiologic Profile of Oral Infection with Alpha, Beta, and Gamma Papillomaviruses in an Asian Chinese Population.

Background: Knowledge of the prevalence of and risk factors for oral human papillomavirus (HPV) infection, especially cutaneous types, is limited. Methods: A population-based study using next-generation sequencing consecutively recruited asymptomatic individuals aged 18-64 years from a proportional sampling of the general population of Hong Kong, according to age groups, gender, and regions of residence. We examined associations of alpha-, beta-, and gamma-HPVs from oral rinse samples with participants' sociodemographics by logistic regression models. Results: The prevalence of oral HPV infection among 1426 ethnic Chinese was 15.5% (95% confidence interval [CI], 13.7%-17.5%), 2.5% (95% CI, 1.8%-3.5%), 11.9% (95% CI, 10.3%-13.6%), and 2.9% (95% CI, 2.1%-3.9%) for any type, alpha-, beta-, and gamma-HPV, respectively. Prevalence of any high-risk HPV was 0.8% (95% CI, 0.4%-1.4%), and that of HPV-16 was 0.4% (95% CI, 0.2%-0.8%). HPV-8 and HPV-98 were the most common beta types detected, while HPV-4 and HPV-SD2R were the most common gamma types. Prevalence of alpha- and beta/gamma-HPV infection showed a similar pattern of increase with age, and was higher in men than women. Smoking, drinking, oral sex, and more sexual partners were associated with alpha-HPV. Teeth brushing before sleep was protective for beta/gamma-HPVs. Discussion: The epidemiologic factors associated with oral infection with alpha-HPVs are different from those of beta/gamma-HPVs, suggesting different modes of acquisition and persistence.

Association between investigator-measured body-mass index and colorectal adenoma: a systematic review and meta-analysis of 168,201 subjects.

The objective of this meta-analysis is to evaluate the odds of colorectal adenoma (CRA) in colorectal cancer screening participants with different body mass index (BMI) levels, and examine if this association was different according to gender and ethnicity. The EMBASE and MEDLINE were searched to enroll high quality observational studies that examined the association between investigator-measured BMI and colonoscopy-diagnosed CRA. Data were independently extracted by two reviewers. A random-effects meta-analysis was conducted to estimate the summary odds ratio (SOR) for the association between BMI and CRA. The Cochran's Q statistic and I2 analyses were used to assess the heterogeneity. A total of 17 studies (168,201 subjects) were included. When compared with subjects having BMI < 25, individuals with BMI 25-30 had significantly higher risk of CRA (SOR 1.44, 95% CI 1.30-1.61; I2 = 43.0%). Subjects with BMI ≥ 30 had similarly higher risk of CRA (SOR 1.42, 95% CI 1.24-1.63; I2 = 18.5%). The heterogeneity was mild to moderate among studies. The associations were significantly higher than estimates by previous meta-analyses. There was no publication bias detected (Egger's regression test, p = 0.584). Subgroup analysis showed that the magnitude of association was significantly higher in female than male subjects (SOR 1.43, 95% CI 1.30-1.58 vs. SOR 1.16, 95% CI 1.07-1.24; different among different ethnic groups (SOR 1.72, 1.44 and 0.88 in White, Asians and Africans, respectively) being insignificant in Africans; and no difference exists among different study designs. In summary, the risk conferred by BMI for CRA was significantly higher than that reported previously. These findings bear implications in CRA risk estimation.

Complete Genome Sequence of a Novel Human Papillomavirus Isolated from Oral Rinse.

A novel human papillomavirus (HPV TG550) isolated from the oral rinse of a Chinese male resident was fully characterized. The L1 open reading frame of HPV TG550 shares 82.5% nucleotide sequence similarity with its closest relative, HPV166, and clusters within the species group Gammapapillomavirus 19.

Global temporal patterns of pancreatic cancer and association with socioeconomic development.

Pancreatic cancer induces a substantial global burden. We examined its global incidence/mortality rates and their correlation with socioeconomic development (Human Development Index [HDI] and Gross Domestic Product [GDP] in 2000 as proxy measures). Data on age-standardized incidence/mortality rates in 2012 were retrieved from the GLOBOCAN database. Temporal patterns in 1998-2007 were assessed for 39 countries according to gender. The Average Annual Percent Change (AAPC) of the incidence/mortality trends was evaluated using joinpoint regression analysis. The age-standardized incidence ranged between 0.8-8.9/100,000. When compared among countries, Brazil (AAPC = 10.4, 95%C.I. = 0.8,21) and France (AAPC = 4.7, 95%C.I. = 3.6,5.9) reported the highest incidence rise in men. The greatest increase in women was reported in Thailand (AAPC = 7, 95%C.I. = 2.1,12.1) and Ecuador (AAPC = 4.3, 95%C.I. = 1.3,7.3). For mortality, the Philippines (APCC = 4.3, 95%C.I. = 2,6.6) and Croatia (AAPC = 2, 95% C.I. = 0,3.9) reported the biggest increase among men. The Philippines (AAPC = 5.8, 95% C.I. 4.5,7.2) and Slovakia (AAPC = 3.1, 95% C.I. 0.9,5.3) showed the most prominent rise among women. Its incidence was positively correlated with HDI (men: r = 0.66; women: r = 0.70) and GDP (men: r = 0.29; women: r = 0.28, all p < 0.05), and similarly for mortality (men: r = 0.67; women: r = 0.72 [HDI]; men: r = 0.23; women: r = 0.28 [GDP]). In summary, the incidence and mortality of pancreatic cancer were rising in many countries, requiring regular surveillance.

International incidence and mortality trends of liver cancer: a global profile.

We examined the global incidence and mortality rates of liver cancer, and evaluated the association between incidence/mortality and socioeconomic development (Human Development Index [HDI] and Gross Domestic Product [GDP]) using linear regression analysis. The average annual percent change (AAPC) of the trends was evaluated from join-point regression analysis. The global incidence of liver cancer varied widely by nine-fold, and was negatively correlated with HDI (men: r = -0.232, p = 0.003; women: r = -0.369, p < 0.001) and GDP per capita (men: r = -0.164, p = 0.036; women: r = -0.212, p = 0.007). Its mortality showed a similarly negative correlation with both indices. The greatest incidence rise in men was observed in Poland (AAPC = 17.5, 95% C.I. = 5.6, 30.9) and Brazil (AAPC = 13.2, 95% C.I. = 5.9, 21.0), whereas Germany (AAPC = 6.6, 95% C.I = 2.0, 11.5) and Norway (AAPC = 6.5, 95% C.I. = 3.2, 10.0) had the greatest increase in women. The mortality rates paralleled the incidence rates in most countries. For mortality, Malta (AAPC = 11.5, 95% C.I. = 3.9, 19.8), Australia (AAPC = 6.8, 95% C.I. = 2.2, 11.5) and Norway (APCC = 5.6, 95% C.I. = 2.8, 8.5) reported the biggest increase among men; whilst Australia (AAPC = 13.4, 95% C.I. = 7.8, 19.4) and Singapore (AAPC = 7.7, 95% C.I. = 4.1, 11.5) showed the most prominent rise among women. These epidemiological data identified countries with potentially increasing trends of liver cancer for preventive actions.

Approaching the Hard-to-Reach in Organized Colorectal Cancer Screening: an Overview of Individual, Provider and System Level Coping Strategies.

BACKGROUND: Despite the proven effectiveness of colorectal cancer (CRC) screening on reduction of CRC mortality, the uptake of CRC screening remains low. Participation rate is one of determinants for the success of organized population-based screening program. This review aims to identify those who are hard-to-reach, and summarize the strategies to increase their screening rate from individual, provider and system levels. METHODS: A systematic search of electronic English databases was conducted on the factors and strategies of uptake in CRC screening for the hard-to-reach population up to May 2017. DISCUSSION: The coverage rate and participation rate are two indexes to identify the hard-to-reach population in organized CRC screening program. However, the homeless, new immigrants, people with severe mental illness, the jail intimates, and people with characteristics including lower education levels and/or low socioeconomic status, living in rural/remote areas, without insurance, and racial minorities are usually recognized as hard-to-reach populations. For them, organized screening programs offer a better coverage, while novel invitation approaches for eligible individuals and multiple strategies from primary care physicians are still needed to enhance screening rates among subjects who are hard-to-reach. Suggestions implied the effectiveness of interventions at the system level, including linkages to general practice; use of decision making tools; enlisting supports from coalition; and the continuum from screening to diagnosis and treatment. CONCLUSION: Organized CRC screening offers a system access to approach the hard-to-reach populations. To increase their uptake, multiple and novel strategies from individual, provider and system levels should be applied. For policymakers, public healthcare providers and community stakeholders, it is a test to tailor their potential needs and increase their participation rates through continuous efforts to eliminate disparities and inequity in CRC screening service.