OBJECTIVE: Diffuse sclerosing variant papillary thyroid carcinoma (DSVPTC) is an uncommon variant of papillary thyroid carcinoma (PTC). The biological behaviors and prognostic outcomes of this variant, however, are still controversial. The aim of this systematic review and meta-analysis is to investigate the prognostic significance and outcomes of DSVPTCs in comparison with classical PTCs (cPTCs).
METHODS: An electronic search was performed in five libraries: PubMed, Scopus, ISI, World Health Organization Global Health Library (WHO GHL) and Virtual Health Library (VHL) in June 2016. Published data were extracted and were pooled into odds ratios (OR), mean differences and corresponding 95% confidence intervals (CI) using random-effect model. Publication bias was analyzed using Egger's regression test and funnel plot observation.
RESULTS: From 315 articles, we included 16 articles comprising 732 DSVPTCs for meta-analysis. Overall, DSVPTC manifested more aggressive clinicopathological behaviors than cPTC such as higher rate of vascular invasion (OR: 5.33; 95% CI: 3.08-9.23), extrathyroidal extension (OR: 2.96; 95% CI: 2.04-4.30), lymph node metastasis (OR: 5.40; 95% CI: 2.82-10.35), distant metastasis (OR: 3.61; 95% CI: 1.89-6.88) and were more likely to relapse (OR: 2.83; 95% CI: 1.59-5.05). DSVPTC patients were associated with a worsened overall survival (HR: 1.89; 95% CI: 1.36-2.62).
CONCLUSION: DSVPTCs should be considered high-risk PTCs because of high propensity for tumor invasion, metastasis, relapse and mortality. Aggressiveness of DSVPTCs might be related to a different molecular pathway than that in cPTCs.

OBJECTIVE: Research suggests that rates of depression among general population samples in Asia may be significantly lower than in much of the rest of the world. However, whether this applies to depression among cancer patients is unclear, which is important to determine in order to identify depression treatment needs among cancer patients in this region. The purpose of the present study was to assess caseness rates of serious depression among general cancer patients in the Southeast Asian nation of Viet Nam.
METHOD: A total of 695 adult cancer patients from three hospitals in Da Nang, Viet Nam served as study participants. They were assessed at one time point for (a) demographic and (b) cancer characteristics, and (c) depression symptoms.
RESULTS: The overall caseness rate for serious depression was 28%. Although rates of depression in general population samples usually are significantly higher in women than men, rates of depression among men and women did not differ significantly among our cancer patients. Higher levels of depressive symptoms were found, however, as a function of lower patient income and education, occupation, cancer stage, and type of cancer, but not marital status or age.
CONCLUSIONS: Caseness rates of depression are significantly elevated by a factor of 10-15 among Vietnamese cancer patients relative to general population epidemiological studies in the same region. Although a number of studies have found that rates of depression tend to be lower in Asian as compared to Western general population samples, depression rates among our Vietnamese cancer patients were similar to those reported among Western cancer patients. This suggests that whatever factors are responsible for the relatively low rates of depression observed in Asian general population samples may not be operating in regards to cancer-related depression. Overall, the value of these findings are not only that they provide information for policy makers in Viet Nam to support depression treatment among cancer patients, but also that they suggest that despite the apparent relatively low overall rates of depression it may be useful for cancer and mental health researchers in the region to conduct similar assessments for their policy makers.

Cancer may be induced by many environmental and physiological conditions. Infections with viruses, bacteria and parasites have been recognized for years to be associated with human carcinogenicity. Here we review current concepts of carcinogenicity and its associations with parasitic infections. The helminth diseases schistosomiasis, opisthorchiasis, and clonorchiasis are highly carcinogenic while the protozoan Trypanosoma cruzi, the causing agent of Chagas disease, has a dual role in the development of cancer, including both carcinogenic and anticancer properties. Although malaria per se does not appear to be causative in carcinogenesis, it is strongly associated with the occurrence of endemic Burkitt lymphoma in areas holoendemic for malaria. The initiation of Plasmodium falciparum related endemic Burkitt lymphoma requires additional transforming events induced by the Epstein-Barr virus. Observations suggest that Strongyloides stercoralis may be a relevant co-factor in HTLV-1-related T cell lymphomas. This review provides an overview of the mechanisms of parasitic infection-induced carcinogenicity.

BACKGROUND/AIM: Patients with gynecological malignancies account for 2% of patients with cerebral metastases. Many patients receive whole-brain irradiation (WBI) alone. Local therapies (resection, stereotactic radiosurgery (SRS)) are becoming more popular. This study compared intracerebral control after local therapy to WBI alone in patients with gynecological malignancies.
PATIENTS AND METHODS: Of 56 patients, 45 received WBI alone, 6 SRS alone and 5 resection plus WBI. Treatment type, age, performance score, cancer site, number of cerebral lesions, metastases outside the brain, recursive partitioning analysis (RPA) class and period from gynecological cancer diagnosis to brain metastasis treatment were evaluated.
RESULTS: On univariate analyses, local therapy (p=0.003), single cerebral lesion (p<0.001) and RPA class 1/2 (p=0.027) were positively related to intracerebral control. On Cox regression analysis, local therapy (p=0.013) and RPA class 1/2 (p=0.014) were significant.
CONCLUSION: Local therapies led to better intracerebral control than WBI alone and should be considered for brain metastasis from gynecological malignancies whenever reasonable.

Objective. Our objective is to develop a computerized scheme for liver tumor segmentation in MR images. Materials and Methods. Our proposed scheme consists of four main stages. Firstly, the region of interest (ROI) image which contains the liver tumor region in the T1-weighted MR image series was extracted by using seed points. The noise in this ROI image was reduced and the boundaries were enhanced. A 3D fast marching algorithm was applied to generate the initial labeled regions which are considered as teacher regions. A single hidden layer feedforward neural network (SLFN), which was trained by a noniterative algorithm, was employed to classify the unlabeled voxels. Finally, the postprocessing stage was applied to extract and refine the liver tumor boundaries. The liver tumors determined by our scheme were compared with those manually traced by a radiologist, used as the "ground truth." Results. The study was evaluated on two datasets of 25 tumors from 16 patients. The proposed scheme obtained the mean volumetric overlap error of 27.43% and the mean percentage volume error of 15.73%. The mean of the average surface distance, the root mean square surface distance, and the maximal surface distance were 0.58 mm, 1.20 mm, and 6.29 mm, respectively.

BACKGROUND: A community-based participatory research (CBPR) project used a lay health worker (LHW) intervention to reduce colorectal cancer screening disparities in the Vietnamese American community.
OBJECTIVES: The study seeks to understand how the community participates in the CBPR project from the perspectives of diverse stakeholders.
METHODS: Qualitative interviews were conducted with 13 community leaders, community-based organization (CBO) representatives, LHW coordinators, and researchers. Interview topics included participation context, expectations, partnership dynamics, benefits, challenges, and community impact. Interviews were audio-recorded and transcribed verbatim. Data analysis used grounded theory.
RESULTS: Community participation was built on trust and relationships that were cultivated and nurtured over decades. This is the first study to document that Vietnamese Americans preferred an informal partnership style, but expected researchers to understand community health issues, norms, and collaboration styles.
CONCLUSIONS: CBPR in underserved communities has their own styles, expectations, benefits, and challenges. Understanding these issues is critical in engaging the community.

Breast cancer is the second leading cause of cancer-related mortality worldwide as most patients often suffer cancer relapse. The reason is often attributed to the presence of cancer stem cells (CSCs). Recent studies revealed that dysregulation of microRNA (miRNA) are closely linked to breast cancer recurrence and metastasis. However, no specific study has comprehensively characterised the CSC characteristic and miRNA transcriptome in spheroid-enriched breast cells. This study described the generation of spheroid MCF-7 cell in serum-free condition and the comprehensive characterisation for their CSC properties. Subsequently, miRNA expression differences between the spheroid-enriched CSC cells and their parental cells were evaluated using next generation sequencing (NGS). Our results showed that the MCF-7 spheroid cells were enriched with CSCs properties, indicated by the ability to self-renew, increased expression of CSCs markers, and increased resistance to chemotherapeutic drugs. Additionally, spheroid-enriched CSCs possessed greater cell proliferation, migration, invasion, and wound healing ability. A total of 134 significantly (p<0.05) differentially expressed miRNAs were identified between spheroids and parental cells using miRNA-NGS. MiRNA-NGS analysis revealed 25 up-regulated and 109 down-regulated miRNAs which includes some miRNAs previously reported in the regulation of breast CSCs. A number of miRNAs (miR-4492, miR-4532, miR-381, miR-4508, miR-4448, miR-1296, and miR-365a) which have not been previously reported in breast cancer were found to show potential association with breast cancer chemoresistance and self-renewal capability. The gene ontology (GO) analysis showed that the predicted genes were enriched in the regulation of metabolic processes, gene expression, DNA binding, and hormone receptor binding. The corresponding pathway analyses inferred from the GO results were closely related to the function of signalling pathway, self-renewability, chemoresistance, tumorigenesis, cytoskeletal proteins, and metastasis in breast cancer. Based on these results, we proposed that certain miRNAs identified in this study could be used as new potential biomarkers for breast cancer stem cell diagnosis and targeted therapy.

Chemically diverse heterocyclic chalcones were prepared and evaluated for cytotoxicity, aiming to push forward potency and selectivity. They were tested against rhabdomyosarcoma (RMS) and noncancerous cell line (LLC-PK1). The influence of heteroaryl patterns on rings A and B was studied. Heterocycle functionalities on both rings, such as phenothiazine, thiophene, furan and pyridine were evaluated. Notably, the introduction of three methoxy groups at positions 3, 4, 5 on ring B appears to be critical for cytotoxicity. The best compound, with potent and selective cytotoxicity (IC50 = 12.51 μM in comparison with the value 10.84 μM of paclitaxel), contains a phenothiazine moiety on ring A and a thiophene heterocycle on ring B. Most of the potential compounds only show weak cytoxicity on the noncancerous cell line LLC-PK1.

In recent decades, platinum compounds have been many contributions in medicine. Development of new drugs from the active platinum compounds as well as nanocarriers for targeted delivery and reducing side effects of the drugs has paid much attention. In the study, nanocomplexes were prepared from aquated species of cisplatin and pluronic-conjugated heparin which distributed in the range of 80-100 nm by Transmission Electron Microscopy and 134 nm by Dynamic light scattering (DLS). Formation of the complex was confirmed by FTIR and DLS. The nanocomplexes exhibited high drug-loading capacity (approximately 42.5% wt/wt at 37 °C and 37.5% wt/wt at 25 °C). In vitro, drug-loaded nanogels showed much slower release profiles of cisplatin CDDP in pH 7.4 (physiological pH) compared with pH 5.5 condition at 37 °C. Moreover, the cytotoxicity assay results also indicated that Hep-F127 was cytocompatible; meanwhile, CDDP-loaded nanocomplex was able to reduce the cytotoxic ability of free CDDP (IC50 = 5.68 ± 0.73 μg/ml), which still maintain a significantly antiproliferative activity on NCI-H460 lung cancer cell. The in vitro preliminarily obtained results indicate that the nanocomplex is a candidate for CDDP delivery which can be studied further in cancer therapy.

Asian Americans are now the most rapidly growing minority group in the USA. Over 60 % of Asian Americans in the USA are immigrants. Cancer has been the leading cause of death among Asian Americans since 1980. Understanding the barriers to screening is essential to reduce the unnecessary burden of cancer. Little is known about colorectal cancer screening behavior among foreign-born Asian Americans and how socio-demographic factors may influence the behavior. Even less is known about disaggregated Asian subgroups. Using data from the Chicago Asian Community Survey, a local health assessment survey of three Asian subgroups in Chicago, Chinese, Cambodian, and Vietnamese, this study found that the colorectal cancer screening rate were much lower among foreign-born Asian Americans in Chicago (30 %) than the national rate for the general population (59 %). Furthermore, we studied disaggregated data to determine colorectal cancer screening differences between communities. Findings from this study provide a critical evidence base to inform future research and intervention designs.

With increasing numbers of patients with unresectable locoregionally advanced (LA) head and neck squamous cell carcinoma (HNSCC) receiving cetuximab/radiotherapy (RT), several guidelines on the early detection and management of skin-related toxicities have been developed. Considering the existing management guidelines for these treatment-induced conditions, clinical applicability and standardization of grading methods has remained a cause of concern globally, particularly in Asian countries. In this study, we attempted to collate the literature and clinical experience across Asian countries to compile a practical and implementable set of recommendations for Asian oncologists to manage skin- and mucosa-related toxicities arising from different types of radiation, with or without the addition of cetuximab or chemotherapy. In December 2013, an international panel of experts in the field of head and neck cancer management assembled for an Asia-Pacific head and neck cancer expert panel meeting in China. The compilation of discussion outcomes of this meeting and literature data ultimately led to the development of a set of recommendations for physicians with regards to the approach and management of dermatological conditions arising from RT, chemotherapy/RT and cetuximab/RT, and similarly for the approach and management of mucositis resulting from RT, with or without the addition of chemotherapy or cetuximab. These recommendations helped to adapt guidelines published in the literature or text books into bedside practice, and may also serve as a starting point for developing individual institutional side-effect management protocols with adequate training and education.

Lichens are symbiotic organisms that produce various unique chemicals that can be used for pharmaceutical purposes. With the aim of screening new anti-cancer agents that inhibit cancer cell motility, we tested the inhibitory activity of seven lichen species collected from the Romanian Carpathian Mountains against migration and invasion of human lung cancer cells and further investigated the molecular mechanisms underlying their anti-metastatic activity. Among them, Alectoria samentosa, Flavocetraria nivalis, Alectoria ochroleuca, and Usnea florida showed significant inhibitory activity against motility of human lung cancer cells. HPLC results showed that usnic acid is the main compound in these lichens, and (+)-usnic acid showed similar inhibitory activity that crude extract have. Mechanistically, β-catenin-mediated TOPFLASH activity and KITENIN-mediated AP-1 activity were decreased by (+)-usnic acid treatment in a dose-dependent manner. The quantitative real-time PCR data showed that (+)-usnic acid decreased the mRNA level of CD44, Cyclin D1 and c-myc, which are the downstream target genes of both β-catenin/LEF and c-jun/AP-1. Also, Rac1 and RhoA activities were decreased by treatment with (+)-usnic acid. Interestingly, higher inhibitory activity for cell invasion was observed when cells were treated with (+)-usnic acid and cetuximab. These results implied that (+)-usnic acid might have potential activity in inhibition of cancer cell metastasis, and (+)-usnic acid could be used for anti-cancer therapy with a distinct mechanisms of action.

INTRODUCTION: It remains largely unknown if there are racial disparities in outcomes of prostate cancer (PCa) for Asian American and Pacific Islanders (PIs) (AAPIs). We examined differences in diagnosis, management, and survival of AAPI ethnic groups, relative to their non-Hispanic White (NHW) counterparts.
METHODS: Patients (n = 891,100) with PCa diagnosed between 1988 and 2010 within the surveillance, epidemiology, and end results database were extracted and stratified by ethnic group: Chinese, Japanese, Filipino, Hawaiian, Korean, Vietnamese, Asian Indian/Pakistani, PI, and Other Asian. The effect of ethnic group on stage at presentation, rates of definitive treatment, and PCa-specific mortality was assessed. The severity at diagnosis was defined as: localized (TxN0M0), regional (TxN1M0), or metastatic (TxNxM1).
RESULTS: Relative to NHWs, Asian Indian/Pakistani, Filipino, Hawaiian, and PI men had significantly worse outcomes. Filipino (odds ratio [OR] = 1.38, 95% CI: 1.27-1.51), Hawaiian, (OR = 1.70, 95% CI: 1.41-2.04), Asian Indian/Pakistani (OR = 1.37, 95% CI: 1.15-1.64), and PI men (OR = 1.90, 95% CI: 1.46-2.49) were more likely to present with metastatic PCa (P<0.001). In patients with localized PCa, Filipino men were less likely to receive definitive treatment (OR = 0.91; 95% CI: 0.84-0.97; P = 0.005). Most AAPI groups had lower rates of PCa death except for Hawaiian (hazard ratio = 1.52; 95% CI: 1.30-1.77; P<0.0001) and PI men (hazard ratio = 1.43; 95% CI: 1.12-1.82; P<0.0001).
CONCLUSIONS: Compared with NHWs, AAPI groups were more likely to present with advanced PCa but had better cancer-specific survival. Conversely, Hawaiian and PI men were at greater risk for PCa-specific mortality. Given the different cancer profiles, our results show that there is a need for disaggregation of AAPI data.

Human hepatocellular carcinoma (HCC) is the most common type of liver cancer, the second most common cause of death from cancer worldwide. A very poor prognosis and a lack of effective treatments make liver cancer a major public health problem, notably in less developed regions, particularly in eastern Asia. This fully justifies the search of new molecules and therapeutic strategies against HCC. Ent-kaurane diterpenoids are natural compounds displaying a broad spectrum of potential therapeutic effects including anticancer activity. In this study, we analyzed the pharmacological properties of a family of ent-kaurane diterpenoids from Croton tonkinensis Gagnep in human HepG2 and Hep3b cell lines, used as cellular reference models for in vitro evaluation of new molecules active on HCC. A structure-related cytotoxicity was observed against both HCC cell lines, enlighting the role of the 16-en-15-one skeleton of ent-kaurane diterpenoids. Cytotoxicity was closely correlated to apoptosis, evidenced by concentration-dependent subG1 cell accumulation, and increased annexin V expression. In addition, subtoxic concentration of ent-kaurane diterpenoid dramatically enhanced the sensitivity of HCC cells to doxorubicin. All together, our data bring strong support to the potential interest of ent-kaurane diterpenoids, alone or in combination with a cytotoxic agent, in cancer and more precisely against HCC.

AIM: Epidermal growth factor receptor (EGFR) mutational status is a crucial biomarker for prediction of response to tyrosine kinase inhibitors in patients with non-small cell lung cancer (NSCLC). Although these mutations have been well characterized in other countries, little is known about the frequency or spectrum of EGFR mutations in Vietnamese NSCLC patients.
METHODS: Using Sanger DNA sequencing, we investigated mutations in EGFR exons 18-21 from 332 patients diagnosed with NSCLC at University of Medicine and Pharmacy, Ho Chi Minh City, Vietnam. DNA was extracted from formalin-fixed, paraffin-embedded tissues, followed by PCR amplification and sequencing.
RESULTS: EGFR mutations were detected in 135 samples (40.7%), of which eight samples carried double mutations. In total, 46 different types of EGFR mutations were found, including six novel mutations (p.K713E, p.K714R, p.P794S, p.R803W, p.P848S, and p.K867E). Among the four exons investigated, exon 19 was most frequently mutated (63 out of 332 patients, 19%), with the p.E746_A750del appearing in 43 samples. Exon 21 was mutated in 56 samples (16.9%), of which 47 were p.L858R. Each of exons 18 and 20 was mutated in 12 samples (3.6%). The frequency of EGFR mutations was higher in females than in males (48.9% vs 35%, P = 0.012), but not statistically different between adenocarcinomas and other histological types of NSCLC (41.3% vs 34.5%, P = 0.478).
CONCLUSION: DNA sequencing detected EGFR mutations with high frequency and revealed a broad spectrum of mutation type in Vietnamese patients with NSCLC.

AIM: To generate a tool that estimates the probability of developing new cerebral metastases after stereotactic radiosurgery (SRS) in breast cancer patients.
PATIENTS AND METHODS: SRS dose plus seven characteristics (age, performance score, number of cerebral metastases, maximum diameter of all metastases, location of metastases, extra-cerebral spread and time from breast cancer diagnosis until SRS) were analyzed regarding their ability to predict the probability of new cerebral metastases development following SRS. For those characteristics deemed significant, points of 0 (higher risk of new lesions) or 1 (lower risk) were given. Scores were generated by adding the points of significant characteristics.
RESULTS: Performance score (p=0.013) and maximum diameter of all metastases (p=0.022) were associated with development of subsequent brain metastases. Two groups were created, 0-1 and 2 points. Freedom from new cerebral metastases rates were 27% and 92%, respectively, at 15 months (p=0.003).
CONCLUSION: This tool helps select breast cancer with few cerebral metastases receiving SRS who may benefit from additional whole-brain irradiation.

PURPOSE: This study explored a causal model explaining fatigue in lung cancer patients currently undertaking Chemotherapy.
METHOD: In this cross-sectional study, a convenience sample of 246 lung cancer patients were recruited from six Oncology centers throughout the north of Vietnam. The hypothesized model, consisting of insomnia, dyspnea, cough, anxiety, stage of disease, physical activity, nutritional status, and number of completed chemotherapy cycles, was constructed based on Piper's Integrated Fatigue Model and a review of the literature.
RESULTS: All factors, except the number of completed chemotherapy cycles significantly affected fatigue. The hypothesized model explained 42.9% of fatigue variance. Dyspnea had the largest total effect on fatigue (β = 0.397, p < 0.01), followed by cough (β = 0.343, p < 0.01), insomnia (β = 0.318 (p < 0.01), and anxiety (β = 0.115, p < 0.05). However, insomnia had the greatest direct effect on fatigue. There was also interplay among those four factors in determining fatigue. Physical activity and nutrition status had small effects on fatigue (β = - 0.148, p < 0.01 and β = - 0.156, p < 0.01).
CONCLUSION: The model fits well to explain fatigue. Having the largest direct effect on fatigue, insomnia appeared as a factor of choice for future fatigue control programs. Due to its higher direct effect on fatigue, dyspnea was recommended over cough for fatigue management. Additionally, the interactions among fatigue, dyspnea, and cough suggested that comprehensive programs, which simultaneously address these three symptoms, would be a promising approach for practitioners to consider.

A new series of vinca-alkaloids derivatives containing various α,β-unsaturated aromatic side chains was synthesized. Four new vinca-alkaloids derivatives showed selective cytotoxicities against KB tumor cell lines with IC50 value below 0.1 μM, thus comparable with vinblastine.

BACKGROUND/AIM: In oncology, elderly people are a separate group of patients requiring special consideration. This applies to the treatment of cerebral metastases as well. The present study focused on elderly patients receiving stereotactic radiosurgery (SRS) for few cerebral lesions.
PATIENTS AND METHODS: In 95 patients aged ≥65 years, two SRS doses, 16-18 Gy (n=44) and 20 Gy (n=51), were compared regarding outcomes of SRS.
RESULTS: The overall intracerebral control rates at 12 months were 30% after 16-18 Gy and 45% after 20 Gy (p=0.53). Twelve-month rates of freedom from new intracerebral lesions were 41% and 52%, respectively (p=0.63). Twelve-month local control rates of the irradiated lesions were 55% and 81%, respectively (p=0.069). Overall survival rates at 12 months were 29% and 31%, respectively (p=0.67).
CONCLUSION: SRS with 16-18 Gy was not significantly inferior to SRS with 20 Gy in elderly patients with few cerebral metastases.

AIM: To develop a predictive tool for survival after stereotactic radiosurgery of brain metastases from colorectal cancer.
PATIENTS AND METHODS: Out of nine factors analyzed for survival, those showing significance (p<0.05) or a trend (p≤0.06) were included. For each factor, 0 (worse survival) or 1 (better survival) point was assigned. Total scores represented the sum of the factor scores.
RESULTS: Performance status (p=0.010) and interval from diagnosis of colorectal cancer until radiosurgery (p=0.026) achieved significance, extracranial metastases showed a trend (p=0.06). These factors were included in the tool. Total scores were 0-3 points. Six-month survival rates were 17% for patients with 0, 25% for those with 1, 67% for those with 2 and 100% for those with 3 points; 12-month rates were 0%, 0%, 33% and 67%, respectively. Two groups were created: 0-1 and 2-3 points. Six- and 12-month survival rates were 20% vs. 78% and 0% vs. 44% (p=0.002), respectively.
CONCLUSION: This tool helps optimize the treatment of patients after stereotactic radiosurgery for brain metastases from colorectal cancer.

Colorectal cancer (CRC) is the third leading cause of global cancer mortality. Recent studies have proposed several gene signatures to predict CRC prognosis, but none of those have proven reliable for predicting prognosis in clinical practice yet due to poor reproducibility and molecular heterogeneity. Here, we have established a prognostic signature of 113 probe sets (CRC-113) that include potential biomarkers and reflect the biological and clinical characteristics. Robustness and accuracy were significantly validated in external data sets from 19 centers in five countries. In multivariate analysis, CRC-113 gene signature showed a stronger prognostic value for survival and disease recurrence in CRC patients than current clinicopathological risk factors and molecular alterations. We also demonstrated that the CRC-113 gene signature reflected both genetic and epigenetic molecular heterogeneity in CRC patients. Furthermore, incorporation of the CRC-113 gene signature into a clinical context and molecular markers further refined the selection of the CRC patients who might benefit from postoperative chemotherapy. Conclusively, CRC-113 gene signature provides new possibilities for improving prognostic models and personalized therapeutic strategies.

Lichens produce various unique chemicals that can be used for pharmaceutical purposes. To screen for novel lichen secondary metabolites showing inhibitory activity against lung cancer cell motility, we tested acetone extracts of 13 lichen samples collected in Chile. Physciosporin, isolated from Pseudocyphellaria coriacea (Hook f. & Taylor) D.J. Galloway & P. James, was identified as an effective compound and showed significant inhibitory activity in migration and invasion assays against human lung cancer cells. Physciosporin treatment reduced both protein and mRNA levels of N-cadherin with concomitant decreases in the levels of epithelial-mesenchymal transition markers such as snail and twist. Physciosporin also suppressed KITENIN (KAI1 C-terminal interacting tetraspanin)-mediated AP-1 activity in both the absence and presence of epidermal growth factor stimulation. Quantitative real-time PCR analysis showed that the expression of the metastasis suppressor gene, KAI1, was increased while that of the metastasis enhancer gene, KITENIN, was dramatically decreased by physciosporin. Particularly, the activity of 3'-untranslated region of KITENIN was decreased by physciosporin. Moreover, Cdc42 and Rac1 activities were decreased by physciosporin. These results demonstrated that the lichen secondary metabolite, physciosporin, inhibits lung cancer cell motility through novel mechanisms of action.

The purpose of this study was to explore the factors associated with Pap testing among married immigrant women of Vietnamese origin residing in Taiwan, including demographics, knowledge of cervical cancer, knowledge of Pap tests, fatalism, attitudes toward cervical cancer, and barriers to receiving Pap tests. A cross-sectional correlational design was used. Data were collected from July 2012 to January 2013. Participants were recruited through snowball sampling in two communities in Southern Taiwan. A total of 451 married immigrant women of Vietnamese origin aged 30 years and over were invited to participate in the study and 427 participated. Data analysis included descriptive statistics and multivariate logistic regression. Participants with no children were significantly less likely to have received a Pap test (odds ratio = 0.278, 95% confidence interval [CI] = 0.135-0.569); each additional point of knowledge about Pap tests increased the likelihood of having a Pap test by 19% (odds ratio = 1.190, 95% CI = 1.093-1.297), and each additional point in barriers to receiving Pap tests decreased the chances of having received a Pap test (odds ratio = 0.714, 95% CI = 0.637-0.800). The results can provide governments with a reference for developing policies for cervical cancer prevention among married immigrant Vietnamese women.

AIM: Patients with cerebral metastases from head and neck cancer are not common. This study aimed to create an instrument for estimating survival in this particular group of patients.
PATIENTS AND METHODS: Survival was significantly influenced by Eastern Cooperative Oncology Group (ECOG) performance score, number of cerebral lesions and extracranial metastatic disease. These characteristics were included in our score.
RESULTS: Scoring was based on 6-month survival data: ECOG 0-1=1 point, ECOG 2-3=0 points, 1-3 cerebral lesions=1 point, ≥4 cerebral lesions=0 points, lack of extracranial metastases=1 point, and presence of extracranial metastases=0 points. Addition of these points for each patient resulted in 0-3 points. Three groups were built comprising 0-1, 2 and 3 points. Six-month survival rates for these groups were 0%, 50% and 100%, respectively.
CONCLUSION: This new instrument guides physicians in choosing optimal irradiation programs for patients with cerebral metastases from head-and-neck cancer.

Although the association between red meat consumption and colorectal cancer (CRC) is well established, the association across subsites of the colon and rectum remains uncertain, as does time of consumption in relation to cancer development. As these relationships are key for understanding the pathogenesis of CRC, they were examined in two large cohorts with repeated dietary measures over time, the Nurses' Health Study (n = 87,108 women, 1980-2010) and Health Professionals Follow-up Study (n = 47,389 men, 1986-2010). Cox proportional hazards regression models generated hazard ratios (HRs) and 95% confidence intervals (CIs), which were pooled by random-effects meta-analysis. In combined cohorts, there were 2,731 CRC cases (1,151 proximal colon, 816 distal colon, and 589 rectum). In pooled analyses, processed red meat was positively associated with CRC risk (per 1 serving/day increase: HR = 1.15, 95% CI: 1.01-1.32; P for trend 0.03) and particularly with distal colon cancer (per 1 serving/day increase; HR = 1.36; 95% CI: 1.09-1.69; P for trend 0.006). Recent consumption of processed meat (within the past 4 years) was not associated with distal cancer. Unprocessed red meat was inversely associated with risk of distal colon cancer and a weak non-significant positive association between unprocessed red meat and proximal cancer was observed (per 1 serving/day increase: distal HR = 0.75; 95% CI: 0.68-0.82; P for trend <0.001; proximal HR = 1.14, 95% CI: 0.92-1.40; P for trend 0.22). Thus, in these two large cohorts of US health professionals, processed meat intake was positively associated with risk of CRC, particularly distal cancer, with little evidence that higher intake of unprocessed red meat substantially increased risk of CRC. Future studies, particularly those with sufficient sample size to assess associations by subsites across the colon are needed to confirm these findings and elucidate potentially distinct mechanisms underlying the relationship between processed meat and subtypes of unprocessed red meat with CRC.

Triple negative breast cancer (TNBC) represents an anomalous subset of breast cancer with a greatly reduced (30%) 5-year survival rate. The enhanced mortality and morbidity of TNBC arises from the high metastatic rate, which requires the acquisition of AnR, a process whereby anchorage-dependent cells become resistant to cell death induced by detachment. In this study TNBC cell lines were selected for AnR, and these cell lines demonstrated dramatic enhancement in the formation of lung metastases as compared with parental cells. Genetic analysis of the AnR subclones versus parental cells via next generation sequencing and analysis of global alternative RNA splicing identified that the mRNA splicing of cytoplasmic polyadenylation element binding 2 (CPEB2), a translational regulator, was altered in AnR TNBC cells. Specifically, increased inclusion of exon 4 into the mature mRNA to produce the CPEB2B isoform was observed in AnR cell lines. Molecular manipulations of CPEB2 splice variants demonstrated a key role for this RNA splicing event in the resistance of cells to anoikis. Specifically, down-regulation of the CPEB2B isoform using siRNA re-sensitized the AnR cell lines to detachment-induced cell death. The ectopic expression of CPEB2B in parental TNBC cell lines induced AnR and dramatically increased metastatic potential. Importantly, alterations in the alternative splicing of CPEB2 were also observed in human TNBC and additional subtypes of human breast cancer tumors linked to a high metastatic rate. Our findings demonstrate that the regulation of CPEB2 mRNA splicing is a key mechanism in AnR and a driving force in TNBC metastasis.

OBJECTIVES: We conducted a cluster randomized controlled study of a lay health worker (LHW) intervention to increase colorectal cancer (CRC) screening rates among Vietnamese Americans, who typically have lower rates than do non-Hispanic Whites.
METHODS: We randomized 64 LHWs to 2 arms. Each LHW recruited 10 male or female participants who had never had CRC screening (fecal occult blood test, sigmoidoscopy, or colonoscopy). Intervention LHWs led 2 educational sessions on CRC screening. Control LHWs led 2 sessions on healthy eating and physical activity. The main outcome was self-reported receipt of any CRC screening at 6 months after the intervention. We conducted the study from 2008 to 2013 in Santa Clara County, California.
RESULTS: A greater proportion of intervention participants (56%) than control participants (19%) reported receiving CRC screening (P < .001). When controlling for demographic characteristics, the intervention odds ratio was 5.45 (95% confidence interval = 3.02, 9.82). There was no difference in intervention effect by participant gender.
CONCLUSIONS: LHW outreach was effective in increasing CRC screening in Vietnamese Americans. Randomized controlled trials are needed to test the effectiveness of LHW outreach for other populations and other health outcomes.

The aim of this study was to evaluate the toxicity and efficacy of radiotherapy concurrent with weekly cisplatin for T3-4 and N0-1 nasopharyngeal cancer. Between 2005 and 2010, 70 patients with nasopharyngeal cancer (T3-4 N0-1 M0, World Health Organization Type 2-3) from Vietnam, Indonesia, Malaysia and Thailand were registered. Patients were treated with 2D radiotherapy concurrent with weekly cisplatin (30 mg/m(2)). Neither adjuvant nor induction chemotherapy was given. Ninety-three percent of the patients completed at least four cycles of weekly cisplatin during radiotherapy. The median total doses for the primary tumor and positive lymph nodes were 70 and 66 Gy, respectively. The median overall treatment time of concurrent chemoradiotherapy was 52 days. No treatment-related deaths occurred. Grade 3-4 acute toxicities of mucositis, nausea/vomiting and leukopenia were observed in 34%, 4% and 4% of patients, respectively. With a median follow-up time of 52 months for the 40 surviving patients, the 3-year local control, locoregional tumor control, distant metastasis-free survival and overall survival rates were 80%, 75%, 74% and 80%, respectively. In conclusion, the current results illustrate that our concurrent chemoradiotherapy regimen was feasible, but disease control remained insufficient. Further research is encouraged in order to improve clinical outcomes.

Constitutive activation of the PI3K/mTOR signaling pathway contributes to carcinogenesis and metastasis in most, if not all, breast cancers. From a chromene backbone reported to inhibit class I PI3K catalytic subunits, several rounds of chemical syntheses led to the generation of a new collection of chromologues that showed enhanced ability to kill PI3K-addicted cancer cells and to inhibit Akt phosphorylation at serine 473, a hallmark of PI3K/mTOR activation. This initial screen uncovered a chromene designated DHM25 that exerted potent antitumor activity against breast tumor cell lines. Strikingly, DHM25 was shown to be a selective and covalent inhibitor of mTOR using biochemical and cellular analyses, modeling, and a large panel of kinase activity assays spanning the human kinome (243 kinases). Finally, in vivo, this novel drug was an efficient inhibitor of growth and metastasis of triple-negative breast cancer cells, paving the way for its clinical application in oncology.

BACKGROUND: "Context" is a mediating construct that significantly influences the initiation and maintenance of program implementation, but it has seldom been studied in process evaluation. This case study describes the contextual factors that encourage or impede the implementation processes of a research-tested program at a Federally Qualified Community Health Center.
METHOD: We conducted 14 key informant interviews with providers, nurses, medical assistants, and clinic staff in leadership and management positions during the 24 months of active implementation. Interview data were analyzed using Atlas.ti software. A written log documenting exposure, adherence, and coverage of the implementation was used to describe implementation fidelity.
RESULTS: Findings indicated that program implementation needs to align with the organization's mission and values. Sensemaking caused individuals to understand the importance of the new process and increased their motivation to follow assigned procedures. Revisions of the implementation process allowed the program to fit better with the clinic's existing workflow. However, permitting flexibility in the delivery of an intervention may result in inconsistent implementation fidelity. In this study, threats to implementation included unanticipated changes in the clinic environment, such as budget cuts to resources and staff turnover as a consequence of the current economic downturn.
CONCLUSIONS: Momentum leading to sustainable implementation requires a continuous team effort and a stable environment; consequently, a successful implementation requires a structure that supports problem solving, communication, and evaluation.