According to the World Health Organization (WHO), cancer is the second-highest cause of mortality worldwide, killing nearly 9.6 million people annually. Despite the advances in diagnosis and treatment during the last couple of decades, it remains a serious concern due to the limitations of currently available cancer management strategies. Therefore, alternative strategies are highly required to overcome these glitches. In addition, many etiological factors such as environmental and genetic factors initiate the activation of the Janus kinase (JAK)-signal transducer and activator of the transcription (STAT) pathway. This aberrant activation of the JAK-STAT pathway has been reported in various disease states, including inflammatory conditions, hematologic malignancies, and cancer. For instance, many patients with myeloproliferative neoplasms carry the acquired gain-of-function JAK2 V617F somatic mutation. This knowledge has dramatically improved our understanding of pathogenesis and has facilitated the development of therapeutics capable of suppressing the constitutive activation of the JAK-STAT pathway. Our aim is not to be expansive but to highlight emerging ideas towards preventive therapy in a modern view of JAK-STAT inhibitors. A series of agents with different specificities against different members of the JAK family of proteins is currently undergoing evaluation in clinical trials. Here we give a summary of how JAK-STAT inhibitors function and a detailed review of current clinical drugs for managing cancer as a new therapeutic approach.
The effect of the urban vs. rural environment on cardiovascular health is an extremely significant issue, nowadays. Up to date, there is a number of studies revealing that there is environmental impact on the prevalence of cardiovascular disease (CVD). The aim of the current systematic review was to investigate the relationship between the natural environment and cardiovascular health, through the differences between urban and rural environments. A literature search was conducted during July 2022-November 2022 using the databases PubMed/Medline, Scopus and Google Scholar (limited to the last 10 years). The search identified four studies that fulfilled the main aim of the present review. Regardless of the limited number of studies, it was shown that the different environments have a great impact on cardiovascular health. Specifically, various factors seem to affect the occurrence of CVDs in both urban and rural environments. The present review highlights the effect of urban vs. rural environment in relation to cardiovascular risk factors. However, there is a necessity for further investigation in this field in order to shed more light on the environmental components with the most significant impact.
Background/aim: Gastric carcinoma (GC) is a highly heterogeneous disease with many subtypes that have different morphologic and molecular characteristics. In the current study, we analyzed immunohistochemical (IHC) and in situ hybridization (ISH) features of GCs and evaluated their association with prognosis and clinicopathological features.
Materials and methods: Three hundred cases analyzed by IHC and ISH for microsatellite stability, p53, e-cadherin, HER2, PD-L1 expression, and Epstein-Barr virus (EBV) status. Cases were classified into five subgroups based on expression profile. The relationships between subgroups, clinicopathological features, and survival were determined.
Results: Ten (3.3%) cases were classified as EBV-associated, 45 (15%) as microsatellite instable (MSI), 73 (24.3%) as EBV-/microsatellite-stable (MSS)/epithelial-mesenchymal-transformation (EMT)-like, 75 (25%) as EBV-/MSS/ non-EMT-like/p53+, and 97 (32.3%) as EBV-/MSS/non-EMT-like/p53-. The MSI subtype had the best overall survival (OS). In contrast, the EBV-/MSS/EMT-like subtype had the poorest OS. The MSI subtype was also related with old age of the patient and antrum-corpus localized tumors, whereas the EBV-/MSS/EMT-like was associated with young age, larger tumor size, and advanced stage presentation. PD-L1 positivity is highly correlated with MSI and EBV-associated subtypes.
Conclusion: Our data demonstrated a link between IHC/ISH characteristics of GC and clinical outcomes. IHC/ISH based molecular classification may be helpful in predicting the survival.
Phytochemicals have the potential to treat resistant cancer. They are delivered to the target site via nano-based carriers. Promising results are seen in preclinical and in vitro models, as phytochemical-based nanoformulations have improved cell cytotoxicity compared to single agents. They can synergistically inhibit cancer cell growth through p53 apoptosis in MCF-7 breast cancer cell lines. Moreover, synergic viability in reproducible glioma models at half inhibitory concentrations has been shown. Through caspase activation, phytochemical-based nanoformulations also increase cell death in 4T1 breast cancer cell lines. They have shown improved cytotoxicity at half inhibitory concentrations compared to single-agent drugs in cervical cancer. In terms of colorectal cancer, they have the potential to arrest cells in the S phase of the cell cycle and synergistically inhibit cell proliferation. In squamous cell carcinoma of the tongue, they inhibit protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathways. This review reports on developments in the therapeutic management of various cancers using phytochemical-based nanoformulations, which have shown potential benefits in the clinical management of cancer patients, halting/slowing the progression of the disease and ameliorating chemotherapy-induced toxicities.
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