Nitric oxide (NO), is a ubiquitous, water soluble, free radical gas, which plays key role in various physiological as well as pathological processes. Over past decades, NO has emerged as a molecule of interest in carcinogenesis and tumor growth progression. However, there is considerable controversy and confusion in understanding its role in cancer biology. It is said to have both tumoricidal as well as tumor promoting effects which depend on its timing, location, and concentration. NO has been suggested to modulate different cancer-related events including angiogenesis, apoptosis, cell cycle, invasion, and metastasis. On the other hand, it is also emerging as a potential anti-oncogenic agent. Strategies for manipulating in vivo production and exogenous delivery of this molecule for therapeutic gain are being investigated. However, further validation and experimental/clinical trials are required for development of novel strategies based on NO for cancer treatment and prevention. This review discusses the range of actions of NO in cancer by performing an online MEDLINE search using relevant search terms and a review of the literature. Various mechanisms by which NO acts in different cancers such as breast, cervical, gastric,colorectal, and head and neck cancers are addressed. It also offers an insight into the dichotomous nature of NO and discusses its novel therapeutic applications for cancer prevention and treatment.

https://link.springer.com/content/pdf/10.1186%2F1477-7819-11-118.pdf

Nitric oxide and cancer: a review.

In this article, we survey the major p53 (TP53) alterations identified in gastric carcinomas and their precursors. These include p53 expression, mutations, and loss of heterozygosity (LOH). Not only are the various abnormalities summarized, but in addition there is a survey of the literature with respect to the impact of these changes on patient prognosis and treatment response. The majority of published studies involve the immunohistochemical detection of the protein. These use different antibodies, different detection techniques, and different methods of interpretation. Therefore not surprisingly, the results of many of the studies are contradictory with one another. Overall, however, it appears that p53 alterations occur early in the development of gastric carcinoma, being present even in the nonneoplastic mucosa and they increase in frequency as one progresses along the pathway of gastric carcinoma development. p53 immunoreactivity is seen in 17%-90.7% of invasive gastric carcinomas. p53 alterations occur much more commonly in proximal lesions than in distal ones, suggesting that the molecular events leading to the development of gastric carcinoma may be very different in proximal vs. distal tumors. p53 mutations occur in 0%-77% of gastric carcinomas. The mutations are distributed widely across the gene from exons 4-11 with hot spots of mutation at codons 175, 248, 273, 282, 245, and 213. G:C>A:T transitions at CpG sites are the commonest type of mutation. At least 60% of carcinomas with mutations also exhibit p53 LOH.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/humu.10180

TP53 and gastric carcinoma: a review.

Esophageal cancer is a common cancer worldwide and has a poor prognosis. The incidence of esophageal squamous cell cancer has been decreasing, whereas the incidence of esophageal adenocarcinoma has been increasing rapidly, particularly in Western men. Squamous cell cancer continues to be the major type of esophageal cancer in Asia, and the main risk factors include tobacco smoking, alcohol consumption, hot beverage drinking, and poor nutrition. In contrast, esophageal adenocarcinoma predominately affects the whites, and the risk factors include smoking, obesity, and gastroesophageal reflux disease. In addition, Asians and Caucasians may have different susceptibilities to esophageal cancer due to different heritage backgrounds. However, comparison studies between these two populations are limited and need to be addressed in the near future. Ethnic differences should be taken into account in preventive and clinical practices.

/pdf/epidemiologic-differences-in-esophageal-cancer-between-asian-147i716ow2.pdf

Epidemiologic differences in esophageal cancer between Asian and Western populations.

Angiogenesis in pre-malignant conditions

Gastric cancer is one of the leading causes of cancer death worldwide. Because of its heterogeneity, gastric cancer has been an interesting model for studying carcinogenesis and tumorigenesis. Various genetic and molecular alterations are found in gastric cancer that underlie the malignant transformation of gastric mucosa during the multistep process of gastric cancer pathogenesis. Although the detailed mechanisms of gastric cancer development remain uncertain, the enhancement in understanding of its molecular biology in recent years has led to a better perspective on the molecular epidemiology, carcinogenesis, and pathogenesis of gastric cancer. More importantly, it is becoming possible to use molecular markers in differential diagnosis, prognostic evaluation, and specific clinical interventions. Because multiple molecular alterations are frequently noted in gastric cancer and because its histology is complex, new technologies for studying its molecular biology are important to further evaluate gastric carcinogenesis. This review describes our current knowledge of the molecular basis of gastric cancer as it relates to molecular epidemiology, multiple molecular alterations in pathogenesis, and molecular determinants of invasion and metastasis, as well as their potential clinical applications.

/pdf/molecular-basis-of-gastric-cancer-development-and-1seg7g711u.pdf

Molecular basis of gastric cancer development and progression.

The growth and metastasis of tumors depend on the development of an adequate blood supply via angiogenesis. Recent studies indicate that the inducible nitric oxide synthase (iNOS), vascular endothelial growth factor (VEGF) and the tumor suppressor p53 are fundamental play-markers of the angiogenic process. Overexpression of iNOS and VEGF has been shown to induce angiogenesis in tumors. P53 suppresses angiogenesis by down-regulating VEGF and iNOS. The correlation of expression of p53, VEGF and iNOS and clinical features in gastric carcinogenesis, however, has not been well characterized. The expression of p53, iNOS and VEGF in gastric precancerous and cancerous lesions and its relation with the clinical features was determined with immunohistochemistry (avidin-biotin-peroxidase complex method) on 55 randomly selected GC patients and 60 symptom-free subjects from the mass survey in the high-incidence area for GC in Henan, northern China. The positive immunostainig rates for p53, iNOS and VEGF in gastric carcinomas were 51%, 44% and 51%, respectively, and correlated well with TNM stages, but did not show significant difference among the groups with different degrees of gastric wall invasion depth by GC. A positive immunostaining reaction for the iNOS protein was significantly correlated with lymph node metastasis (p = 0.019; Spearman correlation coefficient). P53 protein accumulation was higher in the poorly-differentiated gastric carcinoma than in well-differentiated one. In gastric biopsies, no positive immunosatining was observed for p53, iNOS and VEGF in the histologically normal tissue and chronic superficial gastritis (CSG). However, p53, iNOS and VEGF positive immunostaining was observed in the tissues with different severities of lesions of chronic atrophic gastritis (CAG), intestinal metaplasia (IM) and dysplasia (DYS), and the positive rates increased with the lesion progression from CAG to IM to DYS. A high coincidental positive and negative immunostaining rate for p53, iNOS and VEGF was observed both in biopsy samples with CAG, IM and DYS from the symptom-free subjects and in gastric cancer tissue from the GC patients. The present results indicated that p53 protein accumulation and increased expression of iNOS and VEGF might be responsible for gastric carcinogenesis and tumor aggressiveness of gastric cancer.

/pdf/expression-of-p53-inducible-nitric-oxide-synthase-and-zeakeiwbt8.pdf

Expression of p53, inducible nitric oxide synthase and vascular endothelial growth factor in gastric precancerous and cancerous lesions: correlation with clinical features.

Background
Nutrition deficiencies or poverty traditionally have been recognized to be related with increased risk for esophageal cancer (EC) in rural regions at junction of Henan, Hebei, and Shanxi provinces in northern China—the highest incidence area for esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA). Since the 1980s, economic and nutrition condition in these areas have been improved greatly. However, the histopathological types, staging pattern, and occurrence of ESCC and GCA, especially for esophageal adenocarcinoma (EAC), which have been rarely examined in the Chinese population during the past decades in these areas have not been well characterized to date.

Esophageal and gastric cardia cancers on 4238 Chinese patients residing in municipal and rural regions: a histopathological comparison during 24-year period.

Two-dimensional (2D) bismuth oxychalcogenide (Bi2O2X, X refers to S, Se, and Te) is one type of rising semiconductor with excellent electrical transport properties, high photoresponse, and good air stability. However, the research on 2D Bi2O2S is limited. In this work, ultrathin Bi2O2S nanosheets are synthesized by a facile and eco-friendly chemical synthesis method at room temperature. The thickness and lateral sizes are 2-4 nm and 20-40 nm, respectively. The 2D ultrathin Bi2O2S nanosheets have a broad absorption spectrum from ultraviolet (UV) to near-infrared (NIR). Photoelectrochemical (PEC) photodetectors based on 2D Bi2O2S nanosheets are fabricated by a simple drop-casting method. The 2D Bi2O2S-based PEC photodetectors show excellent photodetection performance with a broad photoresponse spectrum from 365 to 850 nm, a high responsivity of 13.0 mA/W, ultrafast response times of 10/45 ms, and good long-term stability at a bias voltage of 0.6 V, which are superior to most 2D material-based PEC photodetectors. Further, the 2D Bi2O2S PEC photodetector can function as a high-performance self-powered broadband photodetector. Moreover, the photoresponse performance can be effectively tuned by the concentration and the kind of electrolyte. Our results demonstrate that 2D Bi2O2S nanosheets hold great promise for application in high-performance optoelectronic devices.

High-Performance Broadband Photoelectrochemical Photodetectors Based on Ultrathin Bi2O2S Nanosheets.

Single‐atom nanozymes (SAzymes) can effectively mimic the metal active centers of natural enzymes at the atomic level owing to their atomically dispersed active sites, thereby maximizing atom utilization efficiency and density of active sites. Hence, SAzymes can be considered the most promising candidates to replace natural enzymes. Herein, a PEGylated mesoporous Mn‐based single‐atom nanozyme (PmMn/SAE) employing a coordination‐assisted polymerization pyrolysis strategy that uses polydopamine for photothermal‐augmented nanocatalytic therapy is designed. PmMn/SAE exhibits excellent multiple enzymatic performance, including catalase‐like, oxidase‐like, and peroxidase (POD)‐like performance, due to the atomically dispersed Mn active species. As a result, PmMn/SAE not only catalyzes the decomposition of endogenous H2O2 to generate O2 for relieving hypoxia inside the tumor but also transfers electrons to O2 to produce superoxide radicals to kill tumor cells. Meanwhile, PmMn/SAE is able to trigger Fenton‐like reactions to generate highly toxic hydroxyl radicals to induce cancer cell apoptosis. The POD‐like catalytic mechanism of mMn/SAE is revealed using experimental results and density functional theory. Furthermor, PmMn/SAE shows good photothermal conversion efficiency (η = 22.1%) in the second near‐infrared region (1064 nm). Both the in vitro and in vivo experimental results indicate that PmMn/SAE can effectively kill cancer cells through photothermal‐enhanced catalytic therapy.

Tumor Response and NIR‐II Photonic Thermal Co‐Enhanced Catalytic Therapy Based on Single‐Atom Manganese Nanozyme

Manganese (Mn) has attracted widespread attention due to its low‐cost, nontoxicity, and valence‐rich transition. Various Mn‐based nanomaterials have sprung up and are employed in diverse fields, particularly Mn‐based nanozymes, which combine the physicochemical properties of Mn‐based nanomaterials with the catalytic activity of natural enzymes, and are attracting a surge of research, especially in the field of biomedical research. In this review, the typical preparation strategies, catalytic mechanisms, advances and perspectives of Mn‐based nanozymes for biomedical applications are systematically summarized. The application of Mn‐based nanozymes in tumor therapy and sensing detection, together with an overview of their mechanism of action is highlighted. Finally, the prospective directions of Mn‐based nanozymes from five perspectives: innovation, activity enhancement, selectivity, biocompatibility, and application broadening are discussed.

Bin Liu

Papers

Expression of p53, inducible nitric oxide synthase and vascular endothelial growth factor in gastric precancerous and cancerous lesions: correlation with clinical features.

Esophageal and gastric cardia cancers on 4238 Chinese patients residing in municipal and rural regions: a histopathological comparison during 24-year period.

High-Performance Broadband Photoelectrochemical Photodetectors Based on Ultrathin Bi2O2S Nanosheets.

Tumor Response and NIR‐II Photonic Thermal Co‐Enhanced Catalytic Therapy Based on Single‐Atom Manganese Nanozyme

Manganese‐Based Nanozymes: Preparation, Catalytic Mechanisms, and Biomedical Applications