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Hypoxia inducible factor-1α (HIF-1α) is an essential regulator of the cellular response to low oxygen concentrations, activating a broad range of genes that provide adaptive responses to oxygen deprivation. HIF-1α is overexpressed in various cancers and therefore represents a considerable chemotherapeutic target. Salternamide A (SA), a novel small molecule that is isolated from a halophilic Streptomyces sp., is a potent cytotoxic agent against a variety of human cancer cell lines. However, the mechanisms by which SA inhibits tumor growth remain to be elucidated. In the present study, we demonstrate that SA efficiently inhibits the hypoxia-induced accumulation of HIF-1α in a time- and concentration-dependent manner in various human cancer cells. In addition, SA suppresses the upstream signaling of HIF-1α, such as PI3K/Akt/mTOR, p42/p44 MAPK, and STAT3 signaling under hypoxic conditions. Furthermore, we found that SA induces cell death by stimulating G2/M cell cycle arrest and apoptosis in human colorectal cancer cells. Taken together, SA was identified as a novel small molecule HIF-1α inhibitor from marine natural products and is potentially a leading candidate in the development of anticancer agents.

Along with its rapid urban development, Ho Chi Minh City (HCMC) in recent years has suffered a high concentration of air pollutants, especially fine particulate matters or PM2.5. A comprehensive study is required to evaluate the air quality conditions and their health impact in this city. Given the lack of adequate air quality monitoring data over a large area of the size of HCMC, an air quality modeling methodology is adopted to address the requirement. Here, by utilizing a corresponding emission inventory in combination with The Air Pollution Model-Chemical Transport Model (TAPM-CTM), the predicted concentration of air pollutants is first obtained for PM2.5, NOx, and SO2. Then by associating the pollutants exposed with the mortality rate from three causes, namely Ischemic Heart Disease (IHD), cardiopulmonary, and lung cancer, the impact of air pollution on human health is obtained for this purpose. Spatial distribution has shown a high amount of pollutants concentrated in the central city with a high density of combustion vehicles (motorcycles and automobiles). In addition, a significant amount of emissions can be observed from stevedoring and harbor activities, including ferries and cargo handling equipment located along the river. Other sources such as household activities also contribute to an even distribution of emission across the city. The results of air quality modeling showed that the annual average concentrations of NO2 were higher than the standard of Vietnam National Technical Regulation on Ambient Air Quality (QCVN 05: 2013 40 µg/m3) and World Health Organization (WHO) (40 µg/m3). The annual average concentrations of PM2.5 were 23 µg/m3 and were also much higher than the WHO (10 µg/m3) standard by about 2.3 times. In terms of public health impacts, PM2.5 was found to be responsible for about 1136 deaths, while the number of mortalities from exposure to NO2 and SO2 was 172 and 89 deaths, respectively. These figures demand some stringent measures from the authorities to potentially remedy the alarming situation of air pollution in HCM City.

Aberrant activation of hepatocyte growth factor (HGF)/c-Met signaling pathway caused by gene amplification or mutation plays an important role in tumorigenesis. Therefore, c-Met is considered as an attractive target for cancer therapy and c-Met inhibitors have been developed with great interests. However, cancers treated with c-Met inhibitors inevitably develop resistance commonly caused by the activation of PI3K/Akt signal transduction pathway. Therefore, the combination of c-Met and PI3Kα inhibitors showed synergistic activities, especially, in c-Met hyperactivated and PIK3CA-mutated cells. In our previous study, we rationally designed and synthesized DFX117(6-(5-(2,4-difluorophenylsulfonamido)-6-methoxypyridin-3-yl)-N-(2-morpholinoethyl) imidazo[1,2-a]pyridine-3-carboxamide) as a novel PI3Kα selective inhibitor. Herein, the antitumor activity and underlying mechanisms of DFX117 against non-small cell lung cancer (NSCLC) cells were evaluated in both in vitro and in vivo animal models. Concurrent targeted c-Met and PI3Kα by DFX117 dose-dependent inhibited the cell growth of H1975 cells (PIK3CA mutation and c-Met amplification) and A549 cells (KRAS mutation). DFX117 subsequently induced G0/G1 cell cycle arrest and apoptosis. These data highlight the significant potential of DFX117 as a feasible and efficacious agent for the treatment of NSCLC patients.

Besides the critical functions in hemostasis, thrombosis and the wounding process, platelets have been increasingly identified as active players in various processes in tumorigenesis, including angiogenesis and metastasis. Once activated, platelets can release bioactive contents such as lipids, microRNAs, and growth factors into the bloodstream, subsequently enhancing the platelet⁻cancer interaction and stimulating cancer metastasis and angiogenesis. The mechanisms of treatment failure of chemotherapeutic drugs have been investigated to be associated with platelets. Therefore, understanding how platelets contribute to the tumor microenvironment may potentially identify strategies to suppress cancer angiogenesis, metastasis, and drug resistance. Herein, we present a review of recent investigations on the role of platelets in the tumor-microenvironment including angiogenesis, and metastasis, as well as targeting platelets for cancer treatment, especially in drug resistance.

Forkhead box (FOX) proteins are multifaceted transcription factors that are significantly implicated in cancer, with various critical roles in biological processes. Herein, we provide an overview of several key members of the FOXA, FOXC, FOXM1, FOXO and FOXP subfamilies. Important pathophysiological processes of FOX transcription factors at multiple levels in a context-dependent manner are discussed. We also specifically summarize some major aspects of FOX transcription factors in association with cancer research such as drug resistance, tumor growth, genomic alterations or drivers of initiation. Finally, we suggest that targeting FOX proteins may be a potential therapeutic strategy to combat cancer.