Current Pharmaceutical Design

Interplay between LncRNA/miRNA and TGF-β Signaling in the Tumorigenesis of Gynecological Cancer

Abstract: Gynecologic cancers are among the most common malignancies with aggressive features and poor prognosis. Tumorigenesis in gynecologic cancers is a complicated process that is influenced by multiple factors, including genetic mutations that activate various oncogenic signaling pathways, including the TGF-β pathway. Aberrant activation of TGF-β signaling is correlated with tumor recurrence and metastasis. It has been shown that non-coding RNAs (ncRNAs) have crucial effects on cancer cell proliferation, migration, and metastasis. Upregulation of various ncRNAs, including long non-coding RNAs (lncRNA) and microRNAs (miRNAs), has been reported in several tumors, like cervical, ovarian, and endometrial cancers, but their cellular mechanisms remain to be investigated. Thus, recognizing the role of ncRNAs in regulating the TGF-β pathway may provide novel strategies for better treatment of cancer patients. The present study summarizes recent findings on the role of ncRNAs in regulating the TGF-β signaling involved in tumor progression and metastasis in gynecologic cancers.

Quercetin and MicroRNA Interplay in Apoptosis Regulation in Ovarian Cancer

The multifaceted nature of ovarian cancer has severely hampered the development of effective therapeutics over the years. The complicate nature of ovarian cancer makes it therapeutically challenging, therefore, there has been a renewed interest in phytochemistry. Phytochemicals have emerged as a potential therapeutic option due to less side effects. Moreover, the signaling inhibition properties have also been studied extensively in recent times. A growing number of data obtained via high-throughput technologies has started to delineate the complex oncogenic signaling networks, thus broadening the therapeutic opportunities. Within the network, microRNAs (miRNAs) have been shown to play a versatile role in the regulation of cancer. Quercetin has been in the spotlight over the years because of its high pharmacological values and substantial evidence has demonstrated its anti-proliferative effect against various types of cancers. Despite the versatility of quercetin, little is known about its anti-proliferative potential towards ovarian cancer. This review sheds some light on quercetin as an alternative therapeutic approach to cancer. Furthermore, we also addresss the interplay between miRNAs and quercetin in the regulation of apoptosis in ovarian cancer.

Nanocellulose-based Delivery Systems and Cervical Cancer: Review of the Literature

It has become clear that targeted therapy is one of the best options for decreasing the unpleasant side effects of existing common methods and reducing the number of deaths occurred due to many types of cancer. Biocompatible and non-toxic delivery systems are provided by nanomedicine for aiding targeted therapy in many diseases containing cancer. Cervical cancer (CC) is not only the most common gynecological cancer but also is ranked as the fourth common cancer between both men and women. Chemotherapy, radiotherapy, surgery, and immunotherapy are the approaches, which are being used for treating CC patients. However, more efficacy of these methods can be achieved with the help of nanomedicine and novel delivery systems. Nanocellulose is one of the agents used for designing these systems in order to deliver different drugs to a diversity of cancerous cells. In this review, we aim to investigate the competency of nanocellulose for establishing novel therapeutic methods for cervical cancer. We hope that our results help develop more drug delivery systems for targeted therapy to reduce the side effects and induce the efficacy of anti-cancer drugs.

Utilizing Plant Phytoconstituents in Metal Oxide Nanoparticle Synthesis for Cancer Therapies

Background: The metal oxide nanoparticles possess unique properties such as biological compatibility, superior reactivity, and capacity to develop reactive oxygen species, due to this they have drawn significant interest in cancer treatment. The various MONPs such as cerium oxide, Copper oxide, Iron oxide, Titanium dioxide, and Zinc oxide have been investigated for several types of cancers including brain, breast, cervical, colon, leukemia, liver, lung, melanoma, ovarian, and prostate cancers. However, traditional physiochemical synthetic methods for MONPs commonly include toxic materials, a major concern that raises questions regarding their biocompatibility and safety. Objective: This study aims to investigate the role of plant phytoconstituents in the development of MONPs via green synthesis and explore the therapeutic effectiveness of MONPs in treating several types of cancer. Primarily, it examines the potential of plant phytoconstituents (phenolic compounds, flavonoids, glycosides, alkaloids, etc.) in the development of MONPs as well as their improved ability to target numerous types of cancer. Methods: A systemic search was conducted on recent literature, focusing on developing green MONPs by utilizing plants' phytoconstituents (plant extracts). The study of plant phytochemicals (present in different parts of a plant such as leaves, flowers, stems, peels, and roots) and their role in the synthesis of green metal oxide nanoparticles as well as their anticancer activity against several types of cancers was analyzed. Also focusing on their anticancer mechanism that involves ROS production, generates oxidative stress, and apoptosis leads to cancer inhibition. Results: Phytochemicals-mediated metal oxide nanoparticle synthesis revealed many advantages such as improved biological compatibility and enhanced sensitivity towards cancer cells. Phytochemicals present in plant extracts act as natural capping, reducing, and stabilizing agents, enhancing nanoparticle synthesis which leads to synergistic anticancer activity. Additionally, the natural antioxidant and anticancer activity of various phytochemicals enhances the therapeutic potential of metal oxide nanoparticles, producing them more effective against ROS-generated apoptosis and showing negligible toxicity towards normal cells. Conclusion: The utilization of plant phytochemicals in metal oxide nanoparticle production presents a safe, eco-friendly, sustainable, and effective approach to developing effective and safer cancer nanomedicines. Green synthesis not only increases anticancer activity but also decreases the biocompatibility problems associated with the physiochemical synthetic approach. Further research needs to concentrate on improving this synergy to create a targeted phytochemical-based metal oxide nanoparticle for cancer therapeutics.

Colloidal Nanocarriers as Versatile Targeted Delivery Systems for Cervical Cancer

Background: The second most common malignant cancer of the uterus is cervical cancer, which is present worldwide, has a rising death rate and is predominant in developing countries. Different classes of anticancer agents are used to treat cervical carcinoma. The use of these agents results in severe untoward side-effects, toxicity, and multidrug resistance (MDR) with higher chances of recurrence and spread beyond the pelvic region. Moreover, the resulting clinical outcome remains very poor even after surgical procedures and treatment with conventional chemotherapy. Because of the nonspecificity of their use, the agents wipe out both cancerous and normal tissues. Colloidal nano dispersions have now been focusing on site-specific delivery for cervical cancer, and there has been much advancement. Methods: This review aims to highlight the problems in the current treatment of cervical cancer and explore the potential of colloidal nanocarriers for selective delivery of anticancer drugs using available literature. Results: In this study, we surveyed the role and potential of different colloidal nanocarriers in cervical cancer, such as nanoemulsion, nanodispersions, polymeric nanoparticles, and metallic nanoparticles and photothermal and photodynamic therapy. We found significant advancement in colloidal nanocarrier-based cervical cancer treatment. Conclusion: Cervical cancer-targeted treatment with colloidal nanocarriers would hopefully result in minimal toxic side effects, reduced dosage frequency, and lower MDR incidence and enhance the patient survival rates. The future direction of the study should be focused more on the regulatory barrier of nanocarriers based on clinical outcomes for cervical cancer targeting with cost-effective analysis.

Human Papillomavirus Selected Properties and Related Cervical Cancer Prevention Issues

High-risk human papillomavirus strains are widely known to be the causative agents responsible for cervical cancer development. Aggregated damage caused by papillomaviruses solely is estimated in at least 5% of all malignancies of the human body and 16% in cancers that affect the female genital area. Enhanced understanding of the complex issue on how the high extent of carcinogenicity is eventually formed due to the infection by the Papoviridae family would contribute to enhancing current prevention strategies not only towards cervical cancer, but also other HPV associated cancers. This review article is aimed at presenting the key points in two directions: the current cervical cancer prevention and related aspects of HPV behavior. Virtually all applied technologies related to HPV diagnostics and screening programs, such as HPV tests, colposcopy-based tests (VIA/VILI), conventional and liquid-based cytology, currently available are presented. Issues of availability, advantages, and drawbacks of the screening programs, as well as vaccination strategies, are also reviewed in the article based on the analyzed sources. The current point of view regarding HPV is discussed with emphasis on the most problematic aspect of the HPV family concerning the observed increasing number of highly carcinogenic types. Present trends in HPV infection diagnostics throughout the human fluids and tissues are also reported, including the latest novelties in this field, such as HPV assay/self-sample device combinations. Besides, a brief outline of the related prevention issues in Kazakhstan, the leading country of Central Asia, is presented. Kazakhstan, as one of the post-soviet middle-income countries, may serve as an example of the current situation in those terrains, concerning the implementation of globally accepted cervical cancer prevention strategies. Along with positive achievements, such as the development of a nationwide screening program, a range of drawbacks is also analyzed and discussed.

An Updated Review Summarizing the Pharmaceutical Efficacy of Genistein and its Nanoformulations in Ovarian Carcinoma

Implementing lifestyle interventions as a primary prevention strategy is a cost-effective approach to reducing the occurrence of cancer, which is a significant contributor to illness and death globally. Recent advanced studies have uncovered the crucial role of nutrients in safeguarding women's health and preventing disorders. Genistein is an abundant isoflavonoid found in soybeans. Genistein functions as a chemotherapeutic drug against various forms of cancer, primarily by modifying apoptosis, the cell cycle, and angiogenesis and suppressing metastasis. Furthermore, Genistein has demonstrated diverse outcomes in women, contingent upon their physiological characteristics, such as being in the early or postmenopausal stages. The primary categories of gynecologic cancers are cervical, ovarian, uterine, vaginal, and vulvar cancers. Understanding the precise mechanism by which Genistein acts on ovarian cancer could contribute to the advancement of anti-breast cancer treatments, particularly in situations where no specific targeted therapies are currently known or accessible. Additional investigation into the molecular action of Genistein has the potential to facilitate the development of a plant-derived cancer medication that has fewer harmful effects. This research could also help overcome drug resistance and prevent the occurrence of ovarian cancers.

The Application of Nanotechnological Therapeutic Platforms against Gynecological Cancers

Abstract: Gynecological cancers (GCs), ovarian, cervical, and endometrial/uterine cancers, are often associated with poor outcomes. Despite the development of several therapeutic modalities against GCs, the effectiveness of the current therapeutic approaches is limited due to their side effects, low therapeutic index, short halflife, and resistance to therapy. To overcome these limitations, nano delivery-based approaches have been introduced with the potential of targeted delivery, reduced toxicity, controlled release, and improved bioavailability of various cargos. This review summarizes the application of different nanoplatforms, such as lipid-based, metal-based, and polymeric nanoparticles, to improve the chemo/radio treatments of GC. In the following work, the use of nanoformulated agents to fight GCs has been mentioned in various clinical trials. Although nanosystems have their own challenges, the knowledge highlighted in this article could provide deep insight into translations of NPs approaches to overcome GCs.

The Circadian Clock as a Potential Biomarker and Therapeutic Target in Gastrointestinal Cancers

: The circadian clock consists of a hierarchical multi-oscillator network of intracellular and intercellular mechanisms throughout the body that contributes to anticipating metabolic activity and maintaining system homeostasis in response to environmental cues and intrinsic stimuli. Over the past few years, genetic variations of core clock genes have been associated with cancer risk in several epidemiological studies. A growing number of epidemiological research studies have demonstrated a direct correlation between the disturbance of circadian rhythms and the growth of tumors, indicating that shift workers are more susceptible to malignancies of the colon, prostate, ovarian, breast, lung, and liver. One of the most related cancers with circadian rhythm is Gastrointestinal (GI) cancer, which is a leading cause of cancer-related mortality nowadays. The aim of this review was to demonstrate the effect of the clock gene network on the growth of GI cancer, providing molecular targets for GI cancer treatment, possible prognostic biomarkers, and guidance for treatment choices.