Epidemiology of nasopharyngeal carcinoma: current insights and future outlook.

Nasopharyngeal carcinoma (NPC) is characterised by its remarkable geographical and ethnic distribution. The interplay between genetic susceptibility, environmental exposures, and Epstein-Barr virus (EBV) infections is indicated in the development of NPC. Exposure to tobacco smoking, dietary factors, and inhalants has been associated with the risk of NPC. Genetic association studies have revealed NPC-associated susceptibility loci, including genes involved in immune responses, xenobiotic metabolism, genome maintenance, and cell cycle regulation. EBV exposure timing and strain variation might play a role in its carcinogenicity, although further investigations are required. Other factors including medical history and oral hygiene have been implicated in NPC. Prevention strategies, including primary prevention and secondary prevention through early detection, are vital in reducing mortality and morbidity of NPC. The current review discusses the global and regional distribution of NPC incidences, the risk factors associated with NPC, and the public health implications of these insights. Future investigations should consider international, large-scale prospective studies to elucidate the mechanisms underlying NPC pathogenesis and develop individualized interventions for NPC.

Precision medicine in nasopharyngeal carcinoma: comprehensive review of past, present, and future prospect.

Nasopharyngeal carcinoma (NPC) is an aggressive malignancy with high propensity for lymphatic spread and distant metastasis. It is prominent as an endemic malignancy in Southern China and Southeast Asia regions. Studies on NPC pathogenesis mechanism in the past decades such as through Epstein Barr Virus (EBV) infection and oncogenic molecular aberrations have explored several potential targets for therapy and diagnosis. The EBV infection introduces oncoviral proteins that consequently hyperactivate many promitotic pathways and block cell-death inducers. EBV infection is so prevalent in NPC patients such that EBV serological tests were used to diagnose and screen NPC patients. On the other hand, as the downstream effectors of oncogenic mechanisms, the promitotic pathways can potentially be exploited therapeutically. With the apparent heterogeneity and distinct molecular aberrations of NPC tumor, the focus has turned into a more personalized treatment in NPC. Herein in this comprehensive review, we depict the current status of screening, diagnosis, treatment, and prevention in NPC. Subsequently, based on the limitations on those aspects, we look at their potential improvements in moving towards the path of precision medicine. The importance of recent advances on the key molecular aberration involved in pathogenesis of NPC for precision medicine progression has also been reported in the present review. Besides, the challenge and future outlook of NPC management will also be highlighted.

Development of semi-quantitative urinary sodium test strip.

Excessive salt consumption has been associated with greater risk of hypertension. Therefore, monitoring of dietary sodium consumption should be prioritized. As sodium is mainly excreted through urine, 24-h urine sample can be used to estimate individual sodium intake. Thus, a simple and inexpensive semi-quantitative urinary sodium detection test strip was developed based on the enzymatic reaction between ß-galactosidase and chlorophenol red-ß-d-galactopyranoside. When tested, color formation was distinguished at 0 M (chartreuse yellow), 0.05 M (sunflower), 0.1-0.15 M (mango tango), and 0.2-0.25 M (persimmon) sodium. Analysis from ImageJ showed a linear result (r2  > 0.9), low SD, and significant increase in magenta difference (p < 0.01) between 0 and 0.05-0.25 M sodium. Test strip can detect 0.03 M sodium at minimum but did not last for >2 days in adverse storage conditions (laboratory conditions, ∼80% relative humidity, 40°C, and direct light exposure) when stored in test strip bottles, and even shorter when exposed to the environment. The presence of urinary potassium, urea, and glucose did not affect test strip performance. Test strip produced comparable results to flame photometry with <15% variation when tested on overnight, random spot, and 24-h urine samples. Overall, the developed test strip can be used to enzymatically semi-quantify 0.05-0.25 M sodium.

Understanding Lung Carcinogenesis from a Morphostatic Perspective: Prevention and Therapeutic Potential of Phytochemicals for Targeting Cancer Stem Cells.

Lung cancer is still one of the deadliest cancers, with over two million incidences annually. Prevention is regarded as the most efficient way to reduce both the incidence and death figures. Nevertheless, treatment should still be improved, particularly in addressing therapeutic resistance due to cancer stem cells-the assumed drivers of tumor initiation and progression. Phytochemicals in plant-based diets are thought to contribute substantially to lung cancer prevention and may be efficacious for targeting lung cancer stem cells. In this review, we collect recent literature on lung homeostasis, carcinogenesis, and phytochemicals studied in lung cancers. We provide a comprehensive overview of how normal lung tissue operates and relate it with lung carcinogenesis to redefine better targets for lung cancer stem cells. Nine well-studied phytochemical compounds, namely curcumin, resveratrol, quercetin, epigallocatechin-3-gallate, luteolin, sulforaphane, berberine, genistein, and capsaicin, are discussed in terms of their chemopreventive and anticancer mechanisms in lung cancer and potential use in the clinic. How the use of phytochemicals can be improved by structural manipulations, targeted delivery, concentration adjustments, and combinatorial treatments is also highlighted. We propose that lung carcinomas should be treated differently based on their respective cellular origins. Targeting quiescence-inducing, inflammation-dampening, or reactive oxygen species-balancing pathways appears particularly interesting.

Identification of Phytochemical-Based ß-Catenin Nuclear Localization Inhibitor in NSCLC: Differential Targeting Population from Member of Isothiocyanates.

Decades of research has convinced us that phytochemical compounds contained within the plant products are the real deal, and they provide benefits such as health maintenance an d cure to illnesses. One of the deadliest noncommunicable diseases today is lung cancer, hence its disease management still deserves attention. Wnt/ß-catenin pathway activation conferring cancer stem cell (CSC) activities to non-small cell lung carcinomas (NSCLCs) may explain why the disease is still difficult to cure. In the present study, we assessed several representatives of phytochemical categories consisting of alkaloids, chalcones and isothiocyanates for their inhibitory activity to nuclear localization of ß-catenin-an important event for Wnt/ß-catenin pathway activation, in lung cancer cell lines. Real-time cell analyzer confirmed that evodiamine (EVO), chelidonine (CHE), isoliquiritigenin (ISO), licochalcone-A (LICO), benzyl isothiocyanate (BI) and phenethylisothiocyanate (PI) exhibited anti-proliferative activities and cytotoxicities to adenocarcinoma cell line SK-LU-1 and human lung CSC primary cell line (HLCSC). Immunofluorescence assay identified that CHE, ISO, LICO, BI and PI were capable of reducing the number of cells harboring ß-catenin within the nuclei of these cells. We extended the characterizations of BI and PI in Wnt-dependent squamous cell carcinoma cell line NCI-H1703 on several CSC functions and found that BI was better at inhibiting soft agar colony formation as an output of self-renewal ability, whereas PI was more effective in inhibiting the growth of multicellular tumor spheroid model mimicking micrometastases. Both however were not able to inhibit migration and invasion of NCI-H1703. In conclusion, BI could potentially be used as a safer alternative to target undifferentiated CSCs as adjuvant therapy, whereas PI could be used as chemotherapy to remove bulk tumor.

Chelerythrine Chloride Downregulates ß-Catenin and Inhibits Stem Cell Properties of Non-Small Cell Lung Carcinoma.

Plant secondary metabolites have been seen as alternatives to seeking new medicines for treating various diseases. Phytochemical scientists remain hopeful that compounds isolated from natural sources could help alleviate the leading problem in oncology-the lung malignancy that kills an estimated two million people annually. In the present study, we characterized a medicinal compound benzophenanthridine alkaloid, called chelerythrine chloride for its anti-tumorigenic activities. Cell viability assays confirmed its cytotoxicity and anti-proliferative activity in non-small cell lung carcinoma (NSCLC) cell lines. Immunofluorescence staining of ß-catenin revealed that there was a reduction of nuclear content as well as overall cellular content of ß-catenin after treating NCI-H1703 with chelerythrine chloride. In functional characterizations, we observed favorable inhibitory activities of chelerythrine chloride in cancer stem cell (CSC) properties, which include soft agar colony-forming, migration, invasion, and spheroid forming abilities. Interesting observations in chelerythrine chloride treatment noted that its action abides to certain concentration-specific-targeting behavior in modulating ß-catenin expression and apoptotic cell death. The downregulation of ß-catenin implicates the downregulation of CSC transcription factors like SOX2 and MYC. In conclusion, chelerythrine chloride has the potential to mitigate cancer growth due to inhibitory actions toward the tumorigenic activity of CSC in lung cancer and it can be flexibly adjusted according to concentration to modulate specific targeting in different cell lines.

A review on the nucleic acid constituents in mushrooms: nucleobases, nucleosides and nucleotides.

Mushrooms have become increasingly important as a reliable food source. They have also been recognized as an important source of bioactive compounds of high nutritional and medicinal values. The nucleobases, nucleosides and nucleotides found in mushrooms play important roles in the regulation of various physiological processes in the human body via the purinergic and/or pyrimidine receptors. Cordycepin, a 3'-deoxyadenosine found in Cordyceps sinensis has received much attention as it possesses many medicinal values including anticancer properties. In this review, we provide a broad overview of the distribution of purine nucleobases (adenine and guanine); pyrimidine nucleobases (cytosine, uracil, and thymine); nucleosides (uridine, guanosine, adenosine and cytidine); as well as novel nucleosides/tides in edible and nonedible mushrooms. This review also discusses the latest research focusing on the successes, challenges, and future perspectives of the analytical methods used to determine nucleic acid constituents in mushrooms. Besides, the exotic taste and flavor of edible mushrooms are attributed to several nonvolatile and water-soluble substances, including the 5'-nucleotides. Therefore, we also discuss the total flavor 5'-nucleotides: 5'-guanosine monophosphate (5'-GMP), 5'-inosine monophosphate (5'-IMP), and 5'-xanthosine monophosphate (5'-XMP) in edible mushrooms.

Revolutionizing the treatment for nasopharyngeal cancer: the impact, challenges and strategies of stem cell and genetically engineered cell therapies.

Nasopharyngeal carcinoma (NPC) is a distinct malignancy of the nasopharynx and is consistently associated with the Epstein-Barr virus (EBV) infection. Its unique anatomical location and complex aetiology often result in advanced-stage disease at first diagnosis. While radiotherapy (RT) and chemotherapy have been the mainstays of treatment, they often fail to prevent tumour recurrence and metastasis, leading to high rates of treatment failure and mortality. Recent advancement in cell-based therapies, such as chimeric antigen receptor (CAR)-T cell therapy, have shown great promise in hematological malignancies and are now being investigated for NPC. However, challenges such as targeting specific tumour antigens, limited T cell persistence and proliferation, and managing treatment-related toxicities must be addressed. Extensive research is needed to enhance the effectiveness and safety of these therapies, paving the way for their integration into standard clinical practice for better management of NPC and a better quality of life for human health.

Panduratin A, a possible inhibitor in metastasized A549 cells through inhibition of NF-kappa B translocation and chemoinvasion.

In the present study, we investigated the effects of panduratin A (PA), isolated from Boesenbergia rotunda, on apoptosis and chemoinvasion in A549 human non-small cell lung cancer cells. Activation of the executioner procaspase-3 by PA was found to be dose-dependent. Caspase-3 activity was significantly elevated at the 5 µg/mL level of PA treatment and progressed to a maximal level. However, no significant elevated level was detected on procaspase-8. These findings suggest that PA activated caspase-3 but not caspase-8. Numerous nuclei of PA treated A549 cells stained brightly by anti-cleaved PARP antibody through High Content Screening. This result further confirmed that PA induced apoptotic cell death was mediated through activation of caspase-3 and eventually led to PARP cleavage. Treatment of A549 cells with PA resulted in a strong inhibition of NF-κB activation, which was consistent with a decrease in nuclear levels of NF-κB/p65 and NF-κB/p50 and the elevation of p53 and p21. Besides that, we also showed that PA significantly inhibited the invasion of A549 cells in a dose-dependent manner through reducing the secretion of MMP-2 of A549 cells gelatin zymography assay. Our findings not only provide the effects of PA, but may also be important in the design of therapeutic protocols that involve targeting of either p53 or NF-κB.

Antidiabetic and antioxidant properties of alkaloids from Catharanthus roseus (L.) G. Don.

Catharanthus roseus (L.) G. Don is a herbal plant traditionally used by local populations in India, South Africa, China and Malaysia to treat diabetes. The present study reports the in vitro antioxidant and antidiabetic activities of the major alkaloids isolated from Catharanthus roseus (L.) G. Don leaves extract. Four alkaloids--vindoline I, vindolidine II, vindolicine III and vindolinine IV--were isolated and identified from the dichloromethane extract (DE) of this plant's leaves. DE and compounds I-III were not cytotoxic towards pancreatic ß-TC6 cells at the highest dosage tested (25.0 µg/mL). All four alkaloids induced relatively high glucose uptake in pancreatic ß-TC6 or myoblast C2C12 cells, with III showing the highest activity. In addition, compounds II-IV demonstrated good protein tyrosine phosphatase-1B (PTP-1B) inhibition activity, implying their therapeutic potential against type 2 diabetes. III showed the highest antioxidant potential in ORAC and DPPH assays and it also alleviated H2O2-induced oxidative damage in ß-TC6 cells at 12.5 µg/mL and 25.0 µg/mL.

The role of Epstein-Barr virus in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a metastasis-prone malignancy closely associated with the Epstein-Barr virus (EBV). Despite ubiquitous infection of EBV worldwide, NPC incidences displayed predominance in certain ethnic groups and endemic regions. The majority of NPC patients are diagnosed with advanced-stage disease, as a result of anatomical isolation and non-specific clinical manifestation. Over the decades, researchers have gained insights into the molecular mechanisms underlying NPC pathogenesis as a result of the interplay of EBV infection with several environmental and genetic factors. EBV-associated biomarkers were also used for mass population screening for the early detection of NPC. EBV and its encoded products also serve as potential targets for the development of therapeutic strategies and tumour-specific drug delivery. This review will discuss the pathogenic role of EBV in NPC and efforts in exploiting the potential of EBV-associated molecules as biomarkers and therapeutic targets. The current knowledge on the role of EBV and its associated products in NPC tumorigenesis, development and progression will offer a new outlook and potential intervention strategy against this EBV-associated malignancy.

Chloroform Fraction of Centratherum anthelminticum (L.) Seed Inhibits Tumor Necrosis Factor Alpha and Exhibits Pleotropic Bioactivities: Inhibitory Role in Human Tumor Cells.

We investigated the antioxidant potential, cytotoxic effect, and TNF-α inhibition activity with NF-κB activation response in a chloroform fraction of Centratherum anthelminticum seeds (CACF). The antioxidant property of CACF was evaluated with DPPH, ORAC, and FRAP assays, which demonstrated significant antioxidant activity. The cytotoxicity of CACF was tested using the MTT assay; CACF effective inhibitory concentrations (IC(50)) for A549, PC-3, MCF-7, and WRL-68 cells were 31.42 ± 5.4, 22.61 ± 1.7, 8.1 ± 0.9, and 54.93 ± 8.3 µg/mL, respectively. CACF effectively and dose-dependently inhibited TNF-α release, in vitro and in vivo. CACF inhibited TNF-α secretion in stimulated RAW264.7 macrophage supernatants with an IC(50) of 0.012 µg/mL, without affecting their viability; the highest dose tested reduced serum TNF-α by 61%. Acute toxicity testing in rats revealed that CACF was non-toxic at all doses tested. Matching the cytotoxic activity towards a mechanistic approach, CACF dose-dependently exhibited in vitro inhibitory effects against the activation of NF-κB translocation in MCF-7 cells. Preliminary phytochemical screening with GC/MS analysis detected 22 compounds in CACF, of which morpholinoethyl isothiocyanate was the most abundant (29.04%). The study reveals the potential of CACF in the treatment of breast cancer and in oxidative stress conditions with associated inflammatory responses.

(-)-Kunstleramide, a new antioxidant and cytotoxic dienamide from the bark of Beilschmiedia kunstleri gamble.

A new dienamide, (2E,4E)-7-(3',4'-dimethoxyphenyl)-N-ethyl-6-(R)-hydroxyhepta- 2,4-dienamide, named (-)-kunstleramide (1), were isolated from the bark of Beilschmiedia kunstleri Gamble together with one neolignan: (+)-kunstlerone (2) and seven known alkaloids: (+)-nornuciferine (3), (-)-isocaryachine (4), (+)-cassythicine (5), (+)-laurotetanine (6), (+)-boldine (7), noratherosperminine (8), (+)-N-demethylphyllocaryptine (9). Their structures were established from spectroscopic techniques, most notably 1D- and 2D-NMR, UV, IR, OR, circular dichroism (CD) spectra and LCMS-IT-TOF. (-)-Kunstleramide (1) exhibited very poor dose-dependent inhibition of DPPH activity, with an IC50 value of 179.5 ± 4.4 µg/mL, but showed a moderate cytotoxic effect on MTT assays of A375, A549, HT-29, PC-3 and WRL-68 with EC50 values of 64.65, 44.74, 55.94, 73.87 and 70.95 µg/mL, respectively.

Impact of different dietary sodium reduction strategies on blood pressure: a systematic review.

High sodium intake was found to be associated with increased blood pressure. Decreasing dietary sodium intake can effectively reduce blood pressure, especially among hypertensive individuals, but the extent of reduction remains debatable. The effectiveness of different sodium reduction strategies on blood pressure reduction was identified in the current review. Randomized controlled trials and clinical trials on dietary sodium intake and blood pressure published from 23 March 2008 to 23 March 2021 were collected from the PubMed database. Twenty-six studies were included and divided into four subgroups based on the types of interventions identified. Subgroups included a low-sodium diet (1) in a group with or without added sodium, (2) through food substitutes, (3) through health education and behavior change, and (4) through salt substitutes. Reduction of dietary sodium intake resulted in a mean difference of 4.51 mmHg (95% CI: 3.35-5.67) in systolic blood pressure and 2.42 mmHg (95% CI: 1.61-3.23) in diastolic blood pressure. The effectiveness of these strategies was approximated from the difference in 24-h urinary sodium excretion between the intervention and control groups, which was 53.74 mmol/day (95% CI: 31.95-75.53). When analyzed, the low-sodium diet without added sodium showed the greatest significant differences in blood pressure (7.58/4.01 mmHg) and 24-h urinary sodium excretion (101.49 mmol/day), whereas the low-sodium diet through food substitutes yielded the lowest significant differences in blood pressure (2.26/0.81 mmHg) and 24-h urinary sodium excretion (25.78 mmol/day). Thus, reducing sodium intake can be an effective strategy for the prevention and treatment of hypertension.

Preparation and Characterization of Chitosan and Inclusive Compound-Layered Gold Nanocarrier to Improve the Antiproliferation Effect of Tamoxifen Citrate in Colorectal Adenocarcinoma (Caco-2) and Breast Cancer (MCF-7) Cells.

Objectives: Cancer diseases have been linked to a huge number of causes that led to deaths in this century along with cardiovascular and lung diseases. Most death-leading types of cancer are colon, lung, breast, and prostate cancers. Due to the remarkable properties of gold (Au) nanocarrier, they are used to deliver and improve tamoxifen (Tam) citrate activity in Caco-2 and MCF-7 cells. Materials and Methods: In this study, preparation of Au nanoparticles (NPs), zeta-potential and size, high resolution transient electron microscopy (HRTEM), high-performance liquid chromatography, ultraviolet-visible spectra, fluorescence microscopy, fourier infrared spectroscopy, and real-time cellular analysis xCELLigence technology were investigated. Results: The zeta-average size of the Tam- ß-cyclodextrin (ß-CD)-hyaluronic acid (HA)-chitosan (Chi)-Au nanocomposite is 82.02 nm with a negative zeta potential of -23.6. Furthermore, HRTEM images showed that, successful formulation of polymer shell around Au core and the Au NP shape is mostly spherical, triangle and irregular. Furthermore, the fluorescence microscope image showed proper cellular uptake of the Tam-ß-CD-HA-Chi-Au nanocomposite in MCF-7 and Caco-2 cells. Additionally, Tam-ß-CD-HA-Chi-Au nanocomposite significantly improved the cytotoxic activity of Tam citrate on Caco-2 cells. IC50 value of Tam reduced from 8.55 µM to 5.32 µM, after 48 h of incubation time (p value <0.00001). Conclusion: This study showed that Tam-ß-CD-HA-Chi-Au nanocomposite is a potential nanocarrier for delivering the drug to Caco-2 and MCF-7 cancer cells, since it has improved Tam citrate activity on colorectal cancer cells. After all, the developed formula showed more effect on Caco-2 than MCF-7. The prepared nanocomposite could be used to improve the cancer therapy in clinical trials.

Nasopharyngeal Carcinoma and Its Microenvironment: Past, Current, and Future Perspectives.

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy that raises public health concerns in endemic countries. Despite breakthroughs in therapeutic strategies, late diagnosis and drug resistance often lead to unsatisfactory clinical outcomes in NPC patients. The tumor microenvironment (TME) is a complex niche consisting of tumor-associated cells, such as fibroblasts, endothelial cells, leukocytes, that influences tumor initiation, progression, invasion, and metastasis. Cells in the TME communicate through various mechanisms, of note, exosomes, ligand-receptor interactions, cytokines and chemokines are active players in the construction of TME, characterized by an abundance of immune infiltrates with suppressed immune activities. The NPC microenvironment serves as a target-rich niche for the discovery of potential promising predictive or diagnostic biomarkers and the development of therapeutic strategies. Thus, huge efforts have been made to exploit the role of the NPC microenvironment. The whole picture of the NPC microenvironment remains to be portrayed to understand the mechanisms underlying tumor biology and implement research into clinical practice. The current review discusses the recent insights into the role of TME in the development and progression of NPC which results in different clinical outcomes of patients. Clinical interventions with the use of TME components as potential biomarkers or therapeutic targets, their challenges, and future perspectives will be introduced. This review anticipates to provide insights to the researchers for future preclinical, translational and clinical research on the NPC microenvironment.

Impacts of particulate matter (PM2.5) on the health status of outdoor workers: observational evidence from Malaysia.

Ambient air pollution is a significant contributor to disease burden, leading to an estimated 4.2 million premature deaths and 103.1 million disability-adjusted life years (DALYs) annually worldwide. As industrialization and urbanization surge in Asia, air pollution and its corresponding health issues follow suit. Findings on disease burden in developing countries are extremely scanty. This study aimed to determine the concentration of PM2.5 and its impact on respiratory health of outdoor workers in Malaysia. A 2-cycled 3-month cohort study involving 440 participants was conducted. Workers' health status was assessed via (1) Total Ocular Symptom Score (TOSS), (2) Total Nasal Symptom Score (TNSS), (3) St. George's Respiratory Questionnaire (SGPQ), and (4) Asthma Control Test (ACT). The maximum PM2.5 concentration was measured at 122.90 ± 2.07 µg/m3 during third week of August 2016. Meanwhile, the minimum concentration was measured at 57.47 ± 3.80 µg/m3 and 57.47 ± 1.64 µg/m3 during fourth week of July 2016 and first week of August 2017 respectively. Findings revealed that TOSS, TNSS, and SGPQ changes were significantly (p < 0.05) associated with the concentration of PM2.5. Outdoor workers were more significantly (p < 0.05) affected by changes in PM2.5 compared to indoor workers with a moderate correlation (r value ranged from 0.4 to 0.7). Ironically, no significant association was found between ACT assessment and PM2.5. Collectively, our findings suggested that changes in the concentration of PM2.5 threatened the respiratory health of outdoor workers. The existing policy should be strengthened and preventive measures to be enforced safeguarding health status of outdoor workers.

Panduratin A inhibits the growth of A549 cells through induction of apoptosis and inhibition of NF-kappaB translocation.

In the present study we investigated the effects of panduratin A, isolated from Boesenbergia rotunda, on proliferation and apoptosis in A549 human non-small cell lung cancer cells. Cell proliferation and induction of apoptosis was determined by the real-time cellular analyzer (RTCA), MTT assay and High Content Screening (HCS). The RTCA assay indicated that panduratin A exhibited cytotoxicity, with an IC50 value of 4.4 µg/mL (10.8 µM). Panduratin A arrested cancer cells labeled with bromodeoxyuridine (BrdU) and phospho-Histone H3 in the mitotic phase. The cytotoxic effects of panduratin A were found to be accompanied by a dose-dependent induction of apoptosis, as assessed by DNA condensation, nuclear morphology and intensity, cell permeability, mitochondrial mass/ potential, F-actin and cytochrome c. In addition, treatment with an apoptosis-inducing concentration of panduratin A resulted in significant inhibition of Nuclear Factor-kappa Beta (NF-κB) translocation from cytoplasm to nuclei activated by tumor necrosis factor-alpha (TNF-α), as illustrated by the HCS assay. Our study provides evidence for cell growth inhibition and induction of apoptosis by panduratin A in the A549 cell line, suggesting its therapeutic potential as an NF-κB inhibitor.

Current Status and Future Perspectives about Molecular Biomarkers of Nasopharyngeal Carcinoma.

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy that shows a remarkable ethnic and geographical distribution. It is one of the major public health problems in some countries, especially Southern China and Southeast Asia, but rare in most Western countries. Multifactorial interactions such as Epstein-Barr virus infection, individual's genetic susceptibility, as well as environmental and dietary factors may facilitate the pathogenesis of this malignancy. Late presentation and the complex nature of the disease have led it to become a major cause of mortality. Therefore, an effective, sensitive, and specific molecular biomarker is urgently needed for early disease diagnosis, prognosis, and prediction of metastasis and recurrence after treatment. In this review, we discuss the recent research status of potential biomarker discovery and the problems that need to be explored further for better NPC management. By studying the aberrant pattern of these candidate biomarkers that promote NPC development and progression, we are able to understand the complexity of this malignancy better, hence positing our stands better towards strategies that may provide a way forward to the discovery of more reliable and specific biomarkers for diagnosis and targeted therapeutic development.

A unique small cell lung carcinoma disease progression model shows progressive accumulation of cancer stem cell properties and CD44 as a potential diagnostic marker.

OBJECTIVES: Cancer stem cells (CSCs) have been implicated in disease progression of aggressive cancers including small cell lung carcinoma (SCLC). Here, we have examined the possible contribution of CSCs to SCLC progression and aggressiveness. MATERIALS AND METHODS: GLC-14, GLC-16 and GLC-19 SCLC cell lines derived from one patient, representing increasing progressive stages of disease were used. CSC marker expressions was determined by RT-qPCR and western blotting analyses, and heterogeneity was studied by CSC marker expression by immunofluorescence microscopy and flow cytometry. Colony formation assays were used to assess stem cell properties and therapy sensitivity. RESULTS: Increasing expression of stem cell markers MYC, SOX2 and particularly CD44 were found in association with advancing disease. Single and overlapping expression of these markers indicated the presence of different CSC populations. The accumulation of more homogeneous double- and triple-positive CSC populations evolved with disease progression. Functional characterization of CSC properties affirmed higher proficiency of colony forming ability and increased resistance to γ-irradiation in GLC-16 and GLC-19 compared to GLC-14. GLC-19 colony formation was significantly inhibited by a human anti-CD44 antibody. CONCLUSION: The progressive increase of MYC, SOX2 and particularly CD44 expression that was accompanied with enhanced colony forming capacity and resistance in the in vitro GLC disease progression model, supports the potential clinical relevance of CSC populations in malignancy and disease relapse of SCLC.