Targeting PI3K/Akt/mTOR Pathway by Different Flavonoids: A Cancer Chemopreventive Approach

Cancer is, globally, one of the main causes of death. Even though various therapies are available, they are still painful because of their adverse side effects. Available treatments frequently fail due to unpromising responses, resistance to classical anticancer drugs, radiation therapy, chemotherapy, and low accessibility to tumor tissues. Developing novel strategies to minimize adverse side effects, improve chemotherapy sensitivity, and control cancer progression is needed. Many studies have suggested small dietary molecules as complementary treatments for cancer patients. Different components of herbal/edible plants, known as flavonoids, have recently garnered attention due to their broad biological properties (e.g., antioxidant, antiviral, antimicrobial, anti-inflammatory, anti-mutagenic, anticancer, hepatoprotective, and cardioprotective). These flavonoids have shown anticancer activity by affecting different signaling cascades. This article summarizes the key progress made in this area and discusses the role of flavonoids by specifically inhibiting the PI3K/Akt/mTOR pathway in various cancers.

Download Full-text

miR-205 in Breast Cancer: State of the Art

International Journal of Molecular Sciences ◽

10.3390/ijms22010027 ◽

2020 ◽

Vol 22 (1) ◽

pp. 27

Author(s):

Ilaria Plantamura ◽

Alessandra Cataldo ◽

Giulia Cosentino ◽

Marilena V. Iorio

Keyword(s):

Breast Cancer ◽

Cancer Progression ◽

Normal Breast ◽

Response To Therapy ◽

Aberrant Expression ◽

Open Questions ◽

Tumor Tissues ◽

Breast Physiology ◽

Cancer Types

Despite its controversial roles in different cancer types, miR-205 has been mainly described as an oncosuppressive microRNA (miRNA), with some contrasting results, in breast cancer. The role of miR-205 in the occurrence or progression of breast cancer has been extensively studied since the first evidence of its aberrant expression in tumor tissues versus normal counterparts. To date, it is known that the expression of miR-205 in the different subtypes of breast cancer is decreasing from the less aggressive subtype, estrogen receptor/progesterone receptor positive breast cancer, to the more aggressive, triple negative breast cancer, influencing metastasis capability, response to therapy and patient survival. In this review, we summarize the most important discoveries that have highlighted the functional role of this miRNA in breast cancer initiation and progression, in stemness maintenance, in the tumor microenvironment, its potential role as a biomarker and its relevance in normal breast physiology—the still open questions. Finally, emerging evidence reveals the role of some lncRNAs in breast cancer progression as sponges of miR-205. Here, we also reviewed the studies in this field.

Download Full-text

Makdonaldyzacja polskiego systemu edukacyjnego

Studia Edukacyjne ◽

10.14746/se.2017.44.19 ◽

1970 ◽

pp. 317-328

Author(s):

Wojciech Welskop

Keyword(s):

Side Effects ◽

Human Activity ◽

Educational System ◽

Consumer Culture ◽

Social Life ◽

And Control

McDonaldization is present in many areas of social life and its various attributes like efficiency,calculability, predictability, and control determine the rhythm of human activity in society. The purpose of this paper is to analyze the educational system in Poland from the perspective of the McDonaldization phenomenon, thereby drawing attention to the role of the consumer culture in the fieldof education and to show the progress of the globalization process and its side effects in this field.

Download Full-text

The Role of miR-107 in Prostate Cancer: A Review and Experimental Evidence

10.5772/intechopen.98281 ◽

2021 ◽

Author(s):

Maria Elizbeth Alvarez-Sanchez ◽

Oscar Rojas Espinosa ◽

Julio César Torres-Romero ◽

Ereth Ameyatzin Robles Chávez ◽

Edgar Estrella-Parra ◽

...

Keyword(s):

Prostate Cancer ◽

Experimental Evidence ◽

Cancer Progression ◽

Signaling Cascades ◽

Potential Utility ◽

Diagnosis And Prognosis ◽

Endogenous Regulators ◽

New Biomarkers

Over the past two decades, several research groups have focused on the functioning of microRNAs (miRNAs), because many of them function as positive or negative endogenous regulators of processes that alter during the development of cancer. Prostate cancer is the second most commonly occurring cancer in men. New biomarkers are needed to support the diagnosis of prostate cancer. Although it is necessary to deepen the research on this molecule to explore its potential utility in the diagnosis, follow-up, and prognosis of cancer, our results support a role of miR-107 in the signaling cascades that allow cancer progression, and as shown here, in the progression of Prostate Cancer (PCa). These findings strongly suggest that miR-107 may be a potential circulating biomarker for the diagnosis and prognosis of prostate cancer.

Download Full-text

The role of HOMER3 in liver cancer progression.

Journal of Global Oncology ◽

10.1200/jgo.2019.5.suppl.89 ◽

2019 ◽

Vol 5 (suppl) ◽

pp. 89-89

Author(s):

Precious Takondwa Makondi

Keyword(s):

Liver Cancer ◽

Viral Hepatitis ◽

Cancer Progression ◽

Alcohol Intake ◽

Clinical Stage ◽

Gene Set Enrichment Analysis ◽

High Expression ◽

Obesity And Diabetes ◽

Tumor Tissues

89 Background: Liver cancer (LC) is in the seventh most common cancer and the fourth largest cause of cancer deaths. Although significant progress has been made in the prevention and treatment of viral hepatitis; alcoholic liver disease, obesity and diabetes are now emerging as major causes for LC. Recently there has been increase in identification of biomarkers which can predict LC risk and disease progression, but the roles of HOMER3 gene in LC are not known. Methods: First the expression of HOMER3 between normal and tumor tissues was determined using The Cancer Genome Atlas (TCGA), Genetic Expression Omnibus (GEO) and protein atlas datasets. HOMER3 expression at different clinical stage and overall survival (OS) was also determined. The role of HOMER3 on OS in relation to cancer stage, hepatitis virus infection and alcohol intake was also determined. STRING database determined HOMER3 interaction network and TCGA was used to verify the correlation status, and the roles of the network genes on OS. The pathways enriched by HOMER3 were determined by Gene Set Enrichment Analysis (GSEA). Results: HOMER3 was significantly highly expressed in tumor tissues as compared to normal tissues. The expression of HOMER3 correlated positively with clinical stage, with highest expression in advanced stages (Stage 3 and 4), and high HOMER3 expression was associated with poor OS. HOMER3’ s high expression was associated with poor OS in advanced stage, alcohol intake, and in those negative of viral hepatitis infection. HOMER3 interacted with HOMER1, SHANK1, GRM5, GRM1, DLGAP1, SHANK2, DLG4, SHANK3, DLG2 and DLGAP4, with positive correlation to HOMER1, SHANK1, GRM5, GRM1, DLGAP1, DLG4 and DLGAP4 and negative correlation to SHANK2, SHANK3 and DLG2. HOMER1 and DLGAP4 high expression were associated with poor OS while SHANK2, SHANK3 and DLG2 high expression were associated with favorable OS. GRM5 and GRM1 high expression were associated with favorable OS despite being positively correlated with HOMER3. ECM receptor interaction and Notch signaling were the upregulated pathways while Metabolism of xenobiotics by cytochrome p450 and PPAR signaling were the downregulated pathways. Conclusions: HOMER3 may is have a role in liver cancer progression of which its targeting may improve LC outcome.

Download Full-text

Role of PI3K-AKT-mTOR Pathway as a Pro-Survival Signaling and Resistance-Mediating Mechanism to Therapy of Prostate Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms222011088 ◽

2021 ◽

Vol 22 (20) ◽

pp. 11088

Author(s):

Thanakorn Pungsrinont ◽

Julia Kallenbach ◽

Aria Baniahmad

Keyword(s):

Prostate Cancer ◽

Early Stage ◽

Resistance Mechanism ◽

Mtor Pathway ◽

Signaling Cascades ◽

Adaptive Responses ◽

Individual Factor ◽

Target Individual ◽

Apoptotic Pathways

Androgen deprivation therapy (ADT) and androgen receptor (AR)-targeted therapy are the gold standard options for treating prostate cancer (PCa). These are initially effective, as localized and the early stage of metastatic disease are androgen- and castration-sensitive. The tumor strongly relies on systemic/circulating androgens for activating AR signaling to stimulate growth and progression. However, after a certain point, the tumor will eventually develop a resistant stage, where ADT and AR antagonists are no longer effective. Mechanistically, it seems that the tumor becomes more aggressive through adaptive responses, relies more on alternative activated pathways, and is less dependent on AR signaling. This includes hyperactivation of PI3K-AKT-mTOR pathway, which is a central signal that regulates cell pro-survival/anti-apoptotic pathways, thus, compensating the blockade of AR signaling. The PI3K-AKT-mTOR pathway is well-documented for its crosstalk between genomic and non-genomic AR signaling, as well as other signaling cascades. Such a reciprocal feedback loop makes it more complicated to target individual factor/signaling for treating PCa. Here, we highlight the role of PI3K-AKT-mTOR signaling as a resistance mechanism for PCa therapy and illustrate the transition of prostate tumor from AR signaling-dependent to PI3K-AKT-mTOR pathway-dependent. Moreover, therapeutic strategies with inhibitors targeting the PI3K-AKT-mTOR signal used in clinic and ongoing clinical trials are discussed.

Download Full-text

Protein Phosphorylation Signaling Cascades in Autism: The Role of mTOR Pathway

Biochemistry (Moscow) ◽

10.1134/s0006297921050072 ◽

2021 ◽

Vol 86 (5) ◽

pp. 577-596

Author(s):

Irina S. Boksha ◽

Tatyana A. Prokhorova ◽

Elena B. Tereshkina ◽

Olga K. Savushkina ◽

Gulnur Sh. Burbaeva

Keyword(s):

Protein Phosphorylation ◽

Mtor Pathway ◽

Signaling Cascades

Download Full-text

The use of hyaluronic acid preparations for the treatment of osteoarthritis of the major joints

Perioperaciina Medicina ◽

10.31636/prmd.v4i2.2 ◽

2021 ◽

Vol 4 (2) ◽

pp. 11-16

Author(s):

O Kalashnikov ◽

O Sulyma ◽

T Osadchuk ◽

V Zayets ◽

T Nizalov ◽

...

Keyword(s):

Side Effects ◽

Adverse Side Effects ◽

Inflammatory Drugs ◽

Anti Inflammatory ◽

High Level ◽

Time Of Administration ◽

Inflammatory Effect ◽

The Ideal

The authors of the article analyzed the experience of domestic and foreign experts in the effectiveness of the use of HA preparations in the treatment of osteoarthritis of major joints. Background and Objective. To analyze the literature sources in order to determine the effectiveness of the use of HA preparations in the treatment of osteoarthritis of major ligaments. Materials and methods. Articles in specialized scientific journals and collections, Internet resource.Results. The analysis of literature sources determined the important role of HA preparations in the supplying and functioning of the articular cartilage. Researchers are inclined to believe that the ideal HA preparation should be as close as possible to the physiological HA of the synovial fluid of the joint. The developed domestic drug Artro-Patch fully corresponds to these parameters. Conclusions. The use of modern injectable HA preparations is advisable at stages 1–3 of OA. Anti-inflammatory effect of HA preparations makes it possible to reduce the dose and time of administration of non-steroidal anti-inflammatory drugs and, as a consequence, reduce the risk of developing many adverse side effects of NSAIDs. The high level of safety of HA preparations, the absence of serious side effects during their long-term use determine their widespread use in the clinical practice of modern orthopedists.

Download Full-text

A Review on the Medicinal Potential of Trachyspermum ammi Found in Pakistan

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2021/v33i41b32369 ◽

2021 ◽

pp. 302-311

Author(s):

Sana Javaid Awan ◽

Faheem Hadi ◽

Tahir Maqbool ◽

Shumaila Nadeem ◽

Sabeen Malik ◽

...

Keyword(s):

Traditional Medicine ◽

Cancer Progression ◽

Treatment Strategies ◽

Herbal Therapy ◽

Adverse Side Effects ◽

Cancer Management ◽

Trachyspermum Ammi ◽

Long Time ◽

And Control ◽

First Time

Numerous plants are used as a traditional medicine in herbal therapy and are well known for their effective potential in therapeutics for different ailments. Carom [Trachyspermum ammi] is one of the plants that are crucial in medicine. It was cultivated first time in different regions of Asia. It has been used in traditional medicine for a long time in a variety of pharmacological and medicinal aspects. It is renowned for its curative value in different miseries, especially infections. Like other fatal diseases, great advancements have been made by utilizing the therapeutic abilities of different medicinal plants regarding the cure and control of cancer progression. However still, there is a need for improvement in treatment strategies and meeting up significant deficiencies in cancer management. Carom may have some progressive role in controlling such types of ailments. Moreover, it may be anticipated as an immunotherapeutic agent and would dominate other infection-controlling agents and cancer-treating strategies due to its higher efficiency as well as biosecurity free of adverse side effects.

Download Full-text

Role of lncRNAs in the Development of an Aggressive Phenotype in Gallbladder Cancer

Journal of Clinical Medicine ◽

10.3390/jcm10184206 ◽

2021 ◽

Vol 10 (18) ◽

pp. 4206

Author(s):

Pablo Pérez-Moreno ◽

Ismael Riquelme ◽

Priscilla Brebi ◽

Juan Carlos Roa

Keyword(s):

Gallbladder Cancer ◽

Cancer Progression ◽

Chemotherapy Resistance ◽

Diagnostic Biomarkers ◽

Regulate Gene Expression ◽

Aggressive Phenotype ◽

Tumor Tissues ◽

Proliferation And Differentiation ◽

Non Coding Rnas

Long non-coding RNAs are sequences longer than 200 nucleotides that are involved in different normal and abnormal biological processes exerting their effect on proliferation and differentiation, among other cell features. Functionally, lncRNAs can regulate gene expression within the cells by acting at transcriptional, post-transcriptional, translational, or post-translational levels. However, in pathological conditions such as cancer, the expression of these molecules is deregulated, becoming elements that can help in the acquisition of tumoral characteristics in the cells that trigger carcinogenesis and cancer progression. Specifically, in gallbladder cancer (GBC), recent publications have shown that lncRNAs participate in the acquisition of an aggressive phenotype in cancer cells, allowing them to acquire increased malignant capacities such as chemotherapy resistance or metastasis, inducing a worse survival in these patients. Furthermore, lncRNAs are useful as prognostic and diagnostic biomarkers since they have been shown to be differentially expressed in tumor tissues and serum of individuals with GBC. Therefore, this review will address different lncRNAs that could be promoting malignant phenotypic characteristics in GBC cells and lncRNAs that may be useful as markers due to their capability to predict a poor prognosis in GBC patients.

Download Full-text

Null effect of circulating sphingomyelins on risk for breast cancer: a Mendelian randomization report using Breast Cancer Association Consortium (BCAC) data

10.1101/19013540 ◽

2019 ◽

Author(s):

Charleen D. Adams

Keyword(s):

Breast Cancer ◽

Cancer Progression ◽

Potential Role ◽

Mendelian Randomization ◽

Signaling Cascades ◽

Cancer Etiology ◽

Null Effect ◽

Cancer Types ◽

The Impact

AbstractBackgroundChanges in cellular metabolism are a hallmark of cancer and are linked with sphingolipid synthesis. Due to immense interest in how sphingolipids influence chemoresistance, more is known about the impact of sphingolipids during cancer treatment and progression than about the potential role of sphingolipids in the induction of tumors in humans.MethodsBecause estrogen triggers sphingolipid signaling cascades, the causal role of circulating levels of sphingomyelin (a type of sphingolipid) on breast cancer was investigated with a well-powered Mendelian randomization design.ResultsThe results reveal a null effect (OR = 0.94; 95% CI = 0.85, 1.05; P = 0.30).ConclusionDespite the role sphingomyelins play during chemoresistance and cancer progression, circulating sphingomyelins do not appear to initiate or protect from breast cancer.ImpactThis finding comprises the first causal report in humans that sphingomyelins on breast cancer initiation is null. Future investigations of risk in other cancer types are needed to further explore the potential role of sphingolipid biology in cancer etiology.

Download Full-text