Evaluating the role of MEN1 gene expression and its clinical significance in breast cancer patients.

BACKGROUND: Breast cancer is a multifactorial disease which involves number of molecular factors that are critically involved in proliferation of breast cancer cells. MEN1 gene that is traditionally known for its germline mutations in neuroendocrine tumors is associated with high risk of developing breast cancer in females with MEN1 syndrome. However, the paradoxical role of MEN1 is reported in sporadic breast cancer cases. The previous studies indicate the functional significance of MEN1 in regulating breast cells proliferation but its relevance in development and progression of breast cancer is still not known. Our study targets to find the role of MEN1 gene aberration and its clinical significance in breast cancer. METHODS: Breast tumor and adjacent normal tissue of 142 sporadic breast cancer patients were collected at the time of surgery. The expression analysis of MEN1 mRNA and protein was done through RT-PCR, immunohistochemistry and western blotting. Further to find the genetic and epigenetic alterations, automated sequencing and MS-PCR was performed respectively. Correlation between our findings and clinical parameters was determined using appropriate statistical tests. RESULTS: MEN1 expression was found to be significantly increased in the breast tumor tissue with its predominant nuclear localization. The elevated expression of MEN1 mRNA (63.38% cases) and protein (60.56% cases) exhibited a significant association with ER status of the patients. Most of the cases had unmethylated (53.52%) MEN1 promoter region, which can be a key factor responsible for dysregulated expression of MEN1 in breast cancer cases. Our findings also revealed the significant association of MEN1 mRNA overexpression with Age and lymph node status of the patients. CONCLUSION: Our results indicate upregulated expression of MEN1 in sporadic breast cancer patients and it could be critically associated with development and advancement of the disease.

HPTLC Stability Indicating Analytical Method of Andrographolide and 5-fluorouracil with Network Pharmacology Analysis against Cancer.

BACKGROUND: Herbal drugs when used in combination with chemotherapeutic drugs can reduce the side effects and increase the efficacy by acting on multiple targets. Andrographolide (AG), a diterpene lactone isolated from Andrographis paniculata Nees, is a bioactive compound with anticancer potential, and 5-fluorouracil (FU), a pyrimidine analogue, is used in the treatment of cancer. Both drugs are used to formulate combination nanoformulation to increase absorption, thereby increasing their oral bioavailability. OBJECTIVE: The study aimed to develop and validate stability indicating simultaneous HPTLC method for quantification of FU and AG in combination nanoformulation along with in silico docking and network pharmacology analysis to understand the interaction between the drugs and cancer targets. METHODS: Chromatographic separation was performed using mobile phase chloroform: methanol: formic acid (9: 0.5: 0.5, v/v/v) on HPTLC silica plates 60 F254 as a stationary phase using UV-Vis detector and HPTLC scanner at 254 nm. Further, in silico docking analysis was performed to predict the binding affinity of AG and FU with different proteins and network pharmacology to find out the exact biomolecular relationship of AG and FU in alleviating cancer. RESULTS: The data from the calibration curve showed a good linear regression relationship with r² = 0.9981 (FU) and r² = 0.9977 (AG) in the concentration range of 0.1-2.0 µg/mL. The developed method was validated according to the ICH guidelines. Stability studies showed changes in peak patterns and areas. Bioinformatic and network pharmacology analyses of AG and FU with target proteins and genes associated with cancer play a multimechanistic role in alleviating cancer. CONCLUSION: The developed method has been concluded to be robust, simple, precise, reproducible, accurate, and stability indicating for simultaneous quantification of AG and FU, and the molecular interaction studies have further indicated that the combination nanoformulation of AG and FU could be effective against cancer.

Phytocompounds targeting epigenetic modulations: an assessment in cancer.

For centuries, plants have been serving as sources of potential therapeutic agents. In recent years, there has been a growing interest in investigating the effects of plant-derived compounds on epigenetic processes, a novel and captivating Frontier in the field of epigenetics research. Epigenetic changes encompass modifications to DNA, histones, and microRNAs that can influence gene expression. Aberrant epigenetic changes can perturb key cellular processes, including cell cycle control, intercellular communication, DNA repair, inflammation, stress response, and apoptosis. Such disruptions can contribute to cancer development by altering the expression of genes involved in tumorigenesis. However, these modifications are reversible, offering a unique avenue for therapeutic intervention. Plant secondary compounds, including terpenes, phenolics, terpenoids, and sulfur-containing compounds are widely found in grains, vegetables, spices, fruits, and medicinal plants. Numerous plant-derived compounds have demonstrated the potential to target these abnormal epigenetic modifications, including apigenin (histone acetylation), berberine (DNA methylation), curcumin (histone acetylation and epi-miRs), genistein (histone acetylation and DNA methylation), lycopene (epi-miRs), quercetin (DNA methylation and epi-miRs), etc. This comprehensive review highlights these abnormal epigenetic alterations and discusses the promising efficacy of plant-derived compounds in mitigating these deleterious epigenetic signatures in human cancer. Furthermore, it addresses ongoing clinical investigations to evaluate the therapeutic potential of these phytocompounds in cancer treatment, along with their limitations and challenges.

Receptor-Mediated Targeting in Breast Cancer through Solid Lipid Nanoparticles and Its Mechanism.

Nanoparticles have gained prominence in many areas and domains worldwide, such as metallic NP, carbon dots, quantum dots, polymeric NP, nano-suspension, nanocrystals, solid lipid nanoparticles (SLN), etc. and have been applied in the field of medicine as nanomedicine with promising results. Rise in cancer mortality rate has been an issue for a long time with female breast cancer as one of the most detected cancers. No permanent treatment has been developed till date could combat breast cancer with minimum side effects that are not long-lasting as there is no proper technique through which the anticancer drugs can recognize benign or malignant or normal cells that causes systematic toxicity. Advancement in technology has led to the discovery of many biological pathways and mechanisms. Tumor cells or cancer cells overexpress some high-affinity receptors that can be targeted to deliver the anticancer drugs at specific site using these pathways and mechanisms. Solid lipid nanoparticles (SLN) are among some of the excellent drug delivery systems, especially stealth SLN (sSLN). SLN, when conjugated with a ligand (called as sSLN), has affinity and specificity towards a specific receptor, and can deliver the drug in breast cancer cells overexpressing the receptors. Using this technique, various investigations have reported better anti-breast cancer activity than simple SLN (non-conjugated to ligand or no receptor targeting). This review includes the investigations and data on receptor-mediated targeting in breast cancer from 2010 to 2021 by searching different databases. Overall, information on SLN in different cancers is reviewed. In vivo investigations, pharmacokinetics, biodistribution, and stability are discussed to describe the efficacy of sSLN. Investigations included in this review demonstrate that sSLN delivers the drug by overcoming the biological barriers and shows enhanced and better activity than non-conjugated SLN which also verifies that a lesser concentration of drug can show anti-breast cancer activity. The efficacy of medicines could be increased with lower cancer deaths through stealth-SLN. Due to the low cost of synthesis, biocompatibility and easy to formulate, more study is needed in vitro and in vivo so that this novel technique could be utilized in the treatment of human breast cancer.

FOXO3 gene hypermethylation and its marked downregulation in breast cancer cases: A study on female patients.

Background: FOXO3, a member of the FOX transcription factor family, is frequently described as being deregulated in cancer. Additionally, notable role of FOXO3 can be easily recognized in the process of ageing and survival. Even though various studies have been done to acknowledge the tumour-suppressive or oncogenic role of FOXO3 in cancer, still there exist a lack of understanding in terms of cancer prognosis and treatment. Therefore, to provide better insight, our study aims to evaluate the role and function of FOXO3 in breast cancer in Indian female patients. We examined the FOXO3 expression levels in breast cancer samples by analyzing mRNA and protein expression along with its clinicopathological parameters. Results: A total of 127 cases of breast cancer with equal normal cases (n=127) were assessed with methylation (MS-PCR), Immunohistochemistry (IHC), mRNA expression using Real-time PCR was analysed and 66.14% cases at mRNA level were found to be downregulated, while 81.10% of cases had little or very little protein expression. Our data state, the promoter hypermethylation of the FOXO3 gene and the downregulated protein expression are significantly correlated (p=0.0004). Additionally, we found a significant correlation between the level of FOXO3 mRNA with ER (p=0.04) and status of lymph node (p=0.01) along with this. Conclusion: Data suggests the prognostic significance and the tumour-suppressive role of FOXO3 in breast cancer cases studied in India. However, there is a need for the extended research targeting FOXO3 to measure its clinical potential and develop well-defined therapeutic strategies.

Anticancer potential of andrographolide from Andrographis paniculata (Burm.f.) Nees and its mechanisms of action.

ETHNOPHARMACOLOGICAL RELEVANCE: Synthetic drugs used for cancer treatment have side effects that may be immunosupressive, can cause liver, kidney and cardiac toxicity, and infertility and ovarian failure, among others. Thus, herbal drugs could be used in the cancer treatment as an adjuvant therapy. Andrographis paniculata (Burm.f.) Nees (AP) is one of the traditional herbs used in different alternative medicinal systems such as Ayurveda, Unani, Chinese, Malayi, Siddha, etc. for the treatment of various disorders and diseases including cancer. AIM OF THE STUDY: The aim of writing this review is to highlight the medicinal importance of AP and its main phytoconstituent andrographolide (AG). The main emphasis was given on the anticancer activity of AG, its proposed mechanisms of action, novel approaches used to improve its biopharmaceutical properties with the perspective of evidence-based research, and its development as an adjuvant therapy for cancer treatment in future. MATERIALS AND METHODS: Literature survey was conducted and research papers were retrieved from different databases such as Pubmed, Google Scholar, ACS, Wiley online library, ScienceDirect, Springer, and Scopus during 1970-2020. Research articles, review articles, and short communications, etc. were used for this purpose. The papers were selected on the basis of exclusion and inclusion criteria. RESULTS: Different anticancer mechanisms of AG have been reportedly proven such as cell cycle arrest, apoptosis, NF-κß inhibition, antiangiogenesis, cytokine inhibition, etc. whereas its pharmacokinetic properties showed its highly protein bound nature, Cyt P400 (CYP) inhibition, low aqueous solubility, poor oral bioavailability, etc. Different novel formulations of AG have been investigated to increase its bioavailability for better efficacy. CONCLUSION: This review can provide knowledge about the potential applicability of AP or AG as an adjuvant therapy in cancer treatment. Further research is needed before making any conclusion about the efficacy in humans as an adjuvant therapy in cancer.

The 100 most influential manuscripts in robotic surgery: a bibliometric analysis.

Since the first robotic assisted surgery in 1985, the number of procedures performed annually has steadily increased. Bibliometric analysis highlights the key studies that have influenced current practice in a field of interest. We use bibliometric analysis to evaluate the 100 most cited manuscripts on robotic surgery and discuss their content and influence on the evolution of the platform. The terms 'robotic surgery,' 'robot assisted surgery' and 'robot-assisted surgery' were used to search Thomson Reuters Web of Science database for full length, English language manuscripts. The top 100 cited manuscripts were analyzed by manuscript type, surgical specialty, first and last author, institution, year and journal of publication. 14,980 manuscripts were returned. Within the top 100 cited manuscripts, the majority featured urological surgery (n = 28), followed by combined results from multiple surgical subspecialties (n = 15) and colorectal surgery (n = 13). The majority of manuscripts featured case series/reports (n = 42), followed by comparative studies (n = 24). The most cited paper authored by Nelson et al. (432 citations) reviewed technological advances in the field. The year and country with the greatest number of publications were 2009 (n = 15) and the USA (n = 68). The Johns Hopkins University published the most top 100 manuscripts (n = 18). The 100 most cited manuscripts reflect the progression of robotic surgery from a basic instrument-holding platform to today's articulated instruments with 3D technology. From feasibility studies to multicenter trials, this analysis demonstrates how robotic assisted surgery has gained acceptance in urological, colorectal, general, cardiothoracic, orthopedic, maxillofacial and neuro surgery.