Polyamidoamine dendrimer decorated graphene oxide as a pH-sensitive nanocarrier for the delivery of hydrophobic anticancer drug quercetin: a remedy for breast cancer.

OBJECTIVES: The aim of this study was to investigate the potential of poly(amido amine) (PAMAM) dendrimer decorated graphene oxide (GO) based nanocarrier for targeted delivery of a hydrophobic anticancer drug, quercetin (QSR). METHODS: GO-PAMAM was successfully synthesized by covalent bonding between GO and NH2-terminated PAMAM dendrimer (zero generation). To investigate drug loading performance, QSR was loaded on the surface of GO as well as GO-PAMAM. Further, the release behaviour of QSR-loaded GO-PAMAM was studied. Finally, an in-vitro sulforhodamine B assay was performed in HEK 293T epithelial cells and MDA MB 231 breast cancer cells. KEY FINDINGS: It was observed that GO-PAMAM shows higher QSR loading capacity compared to GO. Also, synthesized nanocarrier exhibits controlled as well as pH-responsive release of QSR and the amount of QSR released at pH 4 was approximately two times higher than the release at pH 7.4. Furthermore, GO-PAMAM was found to be biocompatible for HEK 293T cells, and a high cytotoxic effect was observed for QSR-loaded GO-PAMAM on MDA MB 231 cells. CONCLUSIONS: The present investigation highlights the potential application of synthesized hybrid materials as a nanocarrier with excellent loading and controlled releasing efficiency for the delivery of the hydrophobic anticancer drug.

Falcipains: Biochemistry, target validation and structure-activity relationship studies of inhibitors as antimalarials.

Malaria is a tropical disease with significant morbidity and mortality burden caused by Plasmodium species in Africa, the Middle East, Asia, and South America. Pathogenic Plasmodium species have lately become increasingly resistant to approved chemotherapeutics and combination therapies. Therefore, there is an emergent need for identifying new druggable targets and novel chemical classes against the parasite. Falcipains, cysteine proteases required for heme metabolism in the erythrocytic stage, have emerged as promising drug targets against Plasmodium species that infect humans. This perspective discusses the biology, biochemistry, structural features, and genetics of falcipains. The efforts to identify selective or dual inhibitors and their structure-activity relationships are reviewed to give a perspective on the design of novel compounds targeting falcipains for antimalarial activity evaluating reasons for hits and misses for this important target.

Dual Drug Loaded Potassium-contained Graphene Oxide as a Nanocarrier in Cocktailed Drug Delivery for the Treatment of Human Breast Cancer.

BACKGROUND: The combinatorial use of anticancer drugs, dual or multiple, with a specific nanocarrier is one of the most promising attempts in drug delivery. The current work reports potassium contained graphene oxide (K-GO) as a nanocarrier in the drug delivery system of two anticancer drugs, gefitinib (GEF) and camptothecin (CPT), simultaneously. METHODS: To characterize K-GO, K-GO-related single and combined drug systems, different techniques have been performed and studied using the following spectroscopic tools, such as Thermo Gravimetric Analysis (TGA 4000), UV-visible spectroscopy, Raman spectroscopy, and Transmission electron microscopy (TEM). The in vitro cytotoxicity tests of K-GO, single drug system, and the combined drug system were also performed in the human breast cancer MDA-MB-231 cells. RESULTS: The release profile of the dual drug conjugates grafted onto the surface of K-GO was found to be up to 38% in PBS solution over 72 hours. The percentage of MDA-MB-231 cell viability was about 18% when treated with K-GO-GEF-CPT combined system; for K-GO, K-GO-GEF, and K-GO-CPT, the cell viability was 79%, 31%, and 32%, respectively. CONCLUSION: We studied the loading, release, and delivery of two anticancer drugs onto the fluorescent nanocarrier. Features, such as superb aqueous solubility, excellent biocompatibility, richness in potassium, and fluorescent nature, which can monitor the delivery of drugs, make them a promising nanocarrier for single or multiple drug delivery. Furthermore, our novel findings revealed that the loading capacity and cytotoxicity of the combined drug-loaded system are superior to the capacity of the individual drug system for human breast cancer cells.

Corrigendum: identification and validation of lncRNA-SNHG17 in lung adenocarcinoma: a novel prognostic and diagnostic indicator.

[This corrects the article DOI: 10.3389/fonc.2022.929655.].

Identification and Validation of lncRNA-SNHG17 in Lung Adenocarcinoma: A Novel Prognostic and Diagnostic Indicator.

Background: Lung cancer has the highest death rate among cancers globally. Accumulating evidence has indicated that cancer-related inflammation plays an important role in the initiation and progression of lung cancer. However, the prognosis, immunological role, and associated regulation axis of inflammatory response-related gene (IRRGs) in non-small-cell lung cancer (NSCLC) remains unclear. Methods: In this study, we perform comprehensive bioinformatics analysis and constructed a prognostic inflammatory response-related gene (IRRGs) and related competing endogenous RNA (ceRNA) network. We also utilized the Pearson's correlation analysis to determine the correlation between IRRGs expression and tumor mutational burden (TMB), microsatellite instability (MSI), tumor-immune infiltration, and the drug sensitivity in NSCLC. Growth curve and Transwell assay used to verify the function of SNHG17 on NSCLC progression. Results: First, we found that IRRGs were significantly upregulated in lung cancer, and its high expression was correlated with poor prognosis; high expression of IRRGs was significantly correlated with the tumor stage and poor prognosis in lung cancer patients. Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment indicated that these IRRGs are mainly involved in the inflammatory and immune response-related signaling pathway in the progression of NSCLC. We utilized 10 prognostic-related genes to construct a prognostic IRRGs model that could predict the overall survival of lung adenocarcinoma (LUAD) patients possessing high specificity and accuracy. Our evidence demonstrated that IRRGs expression was significantly correlated with the TMB, MSI, immune-cell infiltration, and diverse cancer-related drug sensitivity. Finally, we identified the upstream regulatory axis of IRRGs in NSCLC, namely, lncRNA MIR503HG/SNHG17/miR-330-3p/regulatory axis. Finally, knockdown of SNHG17 expression inhibited lung adenocarcinoma (LUAD) cell proliferation and migration. Our findings confirmed that SNHG17 is a novel oncogenic lncRNA and may be a biomarker for the prognosis and diagnosis of LUAD. Conclusion: DNA hypomethylation/lncRNA MIR503HG/SNHG17/microRNA-330-3p/regulatory axis may be a valuable biomarker for prognosis and is significantly correlated with immune cell infiltration in lung cancer.

Polymer grafted magnetic graphene oxide as a potential nanocarrier for pH-responsive delivery of sparingly soluble quercetin against breast cancer cells.

In this work, polymer grafted magnetic graphene oxide (GO-PVP-Fe3O4) was successfully synthesized for efficient delivery of anticancer drug. Firstly, GO was functionalized with the hydrophilic and biocompatible polymer polyvinylpyrrolidone (PVP) and then grafted with magnetic nanoparticles (Fe3O4) through an easy and effective chemical co-precipitation method. Quercetin (QSR) as an anticancer drug was loaded onto the surface of GO-PVP-Fe3O4 via non-covalent interactions. The drug loading capacity was as high as 1.69 mg mg-1 and the synthesized magnetic nanocarrier shows pH-responsive controlled release of QSR. The cellular cytotoxicity of the synthesized nanocarrier with and without drugs was investigated in human breast cancer MDA MB 231 cells and their effects compared on non-tumorigenic epithelial HEK 293T cells. These results reveal that the drug loaded GO-PVP-Fe3O4 nanohybrid was found to be more toxic than the free drug towards MDA MB 231 cells and exhibits biocompatibility towards HEK 293T cells. Overall, a smart drug delivery system including polymer grafted magnetic graphene oxide as a pH-responsive potential nanocarrier could be beneficial for targeted drug delivery, controlled by an external magnetic field as an advancement in chemotherapy against cancer.

Current advances in prognostic and diagnostic biomarkers for solid cancers: Detection techniques and future challenges.

Solid cancers are one of the leading causes of cancer related deaths, characterized by rapid growth of tumour, and local and distant metastases. Current advances on multimodality care have substantially improved local control and metastasis-free survival of patients by resection of primary tumour. The major concern in disease prognosis is the timely detection of resectable or metastatic tumour, thus reinforcing the need for identification of biomarkers for premalignant lesions of solid cancer. This ultimately improves the outcome for the patients. Therefore, the purpose of this review is to update the recent advancements on prognostic and diagnostic biomarkers to enhance early detection of common solid cancers including, breast, lung, colorectal, prostate and stomach cancer. We also provide an insight into Food and Drug Administration (FDA)-approved solid cancers biomarkers; various conventional techniques used for detection of prognostic and diagnostic biomarkers and discuss approaches to turn challenges in this field into opportunities.

Cytotoxic and apoptosis-inducing effects of novel 8-amido isocoumarin derivatives against breast cancer cells.

Isocoumarin is a lactone, a type of natural organic compound that is used as synthetic intermediates of several natural products and pharmaceutical compounds explored for their potential therapeutic applications like antifungal, antimicrobial, anti-inflammatory, and anticancer activities. In our previous work, we were the first group to report the use of amide C-N bond of isatins as the oxidizing directing group for the synthesis of 8-amido isocoumarin derivatives. Whereas in our present work, we have screened the cytotoxic effects of novel 8-amido isocoumarin derivatives (S1-S10) in human breast cancer MCF-7 and MDA-MB-231 cells. Our novel results revealed that N-(3-(4-methoxyphenyl)-1-oxo-4-(4-propylphenyl)-1H-isochromen-8yl)acetamide (S1) and N-(4-(3,5-difluorophenyl)-1-oxo-3-(p-tolyl)-1H-isochromen-8-yl) acetamide (S2) are the two potent compounds among the rest synthesized isocoumarin derivatives that are cytotoxic against MCF-7 and MDA-MB-231 cells, whereas less toxic to the non-tumorigenic IOSE-364 cells. Flow cytometry studies have confirmed the induction of apoptotic effects of compounds by Annexin V/PI double staining. We also observed the cytotoxic effects of S1 and S2, as evaluated by DAPI-PI immunostaining and H&E staining. The morphological alterations consistent with apoptotic blebs were observed in both cancer cells treated with compounds assessed by scanning electron microscopy. Overall, this present study strongly demonstrates that 8-amido isocoumarin derivatives have potent cytotoxic and apoptotic effects in breast cancer cells.

Deficiency in fibroblast PPARß/δ reduces nonmelanoma skin cancers in mice.

The incidence of nonmelanoma skin cancer (NMSC) has been increasing worldwide. Most studies have highlighted the importance of cancer-associated fibroblasts (CAFs) in NMSC progression. However much less is known about the communication between normal fibroblasts and epithelia; disruption of this communication affects tumor initiation and the latency period in the emergence of tumors. Delineating the mechanism that mediates this epithelial-mesenchymal communication in NMSC could identify more effective targeted therapies. The nuclear receptor PPARß/δ in fibroblasts has been shown to modulate adjacent epithelial cell behavior, however, its role in skin tumorigenesis remains unknown. Using chemically induced skin carcinogenesis, we showed that FSPCre-Pparb/dex4 mice, whose Pparb/d gene was selectively deleted in fibroblasts, had delayed emergence and reduced tumor burden compared with control mice (Pparb/dfl/fl). However, FSPCre-Pparb/dex4-derived tumors showed increased proliferation, with no difference in differentiation, suggesting delayed tumor initiation. Network analysis revealed a link between dermal Pparb/d and TGF-ß1 with epidermal NRF2 and Nox4. In vitro investigations showed that PPARß/δ deficiency in fibroblasts increased epidermal Nox4-derived H2O2 production, which triggered an NRF2-mediated antioxidant response. We further showed that H2O2 upregulated NRF2 mRNA via the B-Raf-MEK1/2 pathway. The enhanced NRF2 response altered the activities of PTEN, Src, and AKT. In vivo, we detected the differential phosphorylation profiles of B-Raf, MEK1/2, PTEN, Src, and AKT in the vehicle-treated and chemically treated epidermis of FSPCre-Pparb/dex4 mice compared with that in Pparb/dfl/fl mice, prior to the first appearance of tumors in Pparb/dfl/fl. Our study revealed a role for fibroblast PPARß/δ in the epithelial-mesenchymal communication involved in cellular redox homeostasis.

Multi-biomarker panel signature as the key to diagnosis of ovarian cancer.

Early detection of ovarian cancer has been a challenge to manage the high mortality rate caused by this deadly disease. The trends in mortality have been reduced by the scientific contributions from the corners across the globe, however accounting for the fifth leading cause of gynecological mortality. The complexities in the clinical presentation, origin of tumor, and gene expression profiles had added to much difficulty in understanding and diagnosis of the disease. Stage 1 diagnosis of ovarian cancer improves the 5-year survival rate to around 92%. Cancer antigen-125 (CA-125) is the gold standard tumor marker found at abnormally high levels in the blood of many women in ovarian cancer. However, many non-cancerous conditions exhibit high levels of CA-125 and several women have normal CA-125 level in the early stage of ovarian cancer, suggesting CA-125 biomarker is not specific enough for the screening of early stage ovarian cancer. In addition, several other biomarkers, including HE4 have been added in the diagnostic field for higher sensitivity and specificity in the diagnosis and progression of ovarian cancer. HE4 is a prospective single serum biomarker which has been approved by the FDA to monitor the disease progression in epithelial ovarian cancer. However, owing to low sensitivity and specificity, combination of a panel of biomarkers has been proposed in the diagnosis of the disease. Based on extensive biomarkers research findings, here we discuss current trends in diagnostic approaches and updated potential several panels of cancer biomarkers for early detection of ovarian cancer. It has been recently reported that CA125 in combinations with two or more biomarkers have outperformed single biomarker assays for early detection of the disease. Moreover, CA-125 with CA 19-9, EGFR, G-CSF, Eotaxin, IL-2R, cVCAM, MIF improved the sensitivity with 98.2 % and specificity of 98.7% in early stage detection of ovarian cancer. Overall, this review demonstrates a panel of biomarkers signature as the potential tool for prototype development in future and other advanced approaches for early diagnosis of ovarian cancer to avoid false-diagnosis and excessive cost.

Synthesis, In Vitro Evaluation, Molecular Docking and DFT Studies of Some Phenyl Isothiocyanates as Anticancer Agents.

BACKGROUND: Isothiocyanates (ITCs) are small molecules that are important in synthetic organic chemistry, but their actual importance lies in their potential as anti-carcinogens. Through this piece of work, an effort was made to assess the anti-cancer activity of some simple ITCs which can be synthesized through easy greener pathways. METHODS: Cell proliferation assay was performed on ovarian cancer cells (PA-1) and non-tumorigenic ovarian epithelial cells (IOSE-364). Furthermore, qRT-PCR for transcript expression levels of Spindlin1 and caspases in ovarian cancer cells and cell cycle analysis was performed. In silico studies were incorporated to understand the mode of ligand-protein interaction, ADME/Toxicity and drug-likeliness parameters. Density functional theory studies have been also been employed on the ITCs to assess their efficiency in anticancer activity. RESULTS: An inexpensive, environmentally benign pathway has been developed for synthesizing a series of ITCs. Among the synthesized ITCs, NC6 showed better cytotoxic effects as compared to its counterparts. Novel findings revealed that NC6 had 5-folds lower transcript expression levels of Spindlin1 and induced caspases 3 and 7 expressions assessed by qRT-PCR in ovarian cancer cells. Furthermore, flow cytometry assay showed the cell cycle arrest at G1/S phase of cell cycle. The molecular docking studies revealed favorable binding affinities and the physiochemical parameters were predicted to be compatible with drug-likeliness. CONCLUSION: The results demonstrated the possibility that small isothiocyanate molecules which can be synthesized by a simple green methodology, can pose as promising candidates for their application as anticancer agents.

Epithelial-mesenchymal transition of cancer cells using bioengineered hybrid scaffold composed of hydrogel/3D-fibrous framework.

Cancer cells undergoing epithelial-mesenchymal transition (EMT) acquire stem cell-like phenotype associated with malignant behaviour, chemoresistance, and relapse. Current two-dimensional (2D) in-vitro culture models of tumorigenesis are inadequate to replicate the complexity of in-vivo microenvironment. Therefore, the generation of functional three-dimensional (3D) constructs is a fundamental prerequisite to form multi-cellular tumour spheroids for studying basic pathological mechanisms. In this study, we focused on two major points (i) designing and fabrication of 3D hybrid scaffolds comprising electrospun fibers with cancer cells embedded within hydrogels, and (ii) determining the potential roles of 3D hybrid scaffolds associated with EMT in cancer progression and metastasis. Our findings revealed that 3D hybrid scaffold enhances cell proliferation and induces cancer cells to undergo EMT, as demonstrated by significant up-regulation of EMT associated transcriptional factors including Snail1, Zeb1, and Twist2; and mesenchymal markers whereas epithelial marker, E-Cadherin was downregulated. Remarkably, this induction is independent of cancer cell-type as similar results were obtained for breast cancer cells, MDA-MB-231 and gastric cancer cells, MKN74. Moreover, the hybrid scaffolds enrich aggressive cancer cells with stem cell properties. We showed that our 3D scaffolds could trigger EMT of cancer cells which could provide a useful model for studying anticancer therapeutics against metastasis.

Tumor metastasis suppressor functions of Ets transcription factor through integrin ß3-mediated signaling pathway.

Prostate-derived Ets transcription factor (PDEF) is a member of the Ets transcription factor family originally identified in prostate tissue. PDEF functions like a tumor metastasis suppressor. Although the underlying mechanism is not very clear. In this study, a significantly higher expression level of integrin ß3 was observed in aggressive prostate cancer (PCa) cells; PC3, that lack the expression of PDEF, was confirmed by quantitative real-time polymerase chain reaction and the immunoblot analysis. Dual immunofluorescence studies have confirmed the lower expression of PDEF and higher expression level of integrin ß3 in PCa cells compared with non-tumorigenic prostate epithelial RWPE-1 cells. Then, it was attempted to identify integrin ß3-mediated downstream signaling pathways that modulate actin cytoskeleton remodeling in PCa cells. Inhibition of PDEF by RNA interference (PDEFKD ) in DU145 cells confirmed by transcript and western blot analysis, exhibited significantly higher expression level of integrin ß3 and its downstream signaling molecules talin and paxillin, associated with promoting migration and invasion of cells. Given the involvement of integrin-mediated invasion of cells, PDEFKD DU145 cells were treated with Echistatin, a potent integrin ß3-specific antagonist and found that the cells significantly reduced the transcript and protein expression levels of talin and paxillin; and reduced the invasion of cells. Overall, the cytoskeleton remodeling by integrin ß3, modulated by PDEF, may represent a novel molecular link with cell adhesion and migration leading to the suppression of metastasis in PCa cells.

Functionalized graphene oxide as a nanocarrier for dual drug delivery applications: The synergistic effect of quercetin and gefitinib against ovarian cancer cells.

Graphene Oxide (GO) has been extensively studied in the field of biomedical sciences as one of the most promising biomaterials due to its exceptional physiochemical properties. Experts have long favored anticancer drug cocktails over single drugs, given that the former may provide a more balanced molecular basis for novel chemotherapeutic strategies. Here, we investigated a combinatorial anticancer drug treatment involving the well-proven anticancer drugs quercetin and gefitinib and compared it with gefitinib and quercetin loaded separately onto polyvinylpyrrolidone (PVP)-functionalized graphene oxide (GO-PVP). The loading and cancer cell cytotoxicity of the individual drug systems and their combined loading onto GO-PVP nanovehicles were investigated in PA-1 ovarian cancer cells and compared to their effects on IOSE-364 ovarian epithelial cells. In this report, the combined drug system loaded on the GO-PVP nanovehicle was found to be significantly more toxic than the individual drug loaded systems, as well as the free drugs, toward PA-1 cells compared to the toxicity toward IOSE-364 cells. The combined drug system loaded on the GO-PVP nanovehicle is likely to be more successful than individual drug therapy, given the stronger impact of the combinatorial approach and the efficiency of chemotherapeutic delivery.

The basics of epithelial-mesenchymal transition (EMT): A study from a structure, dynamics, and functional perspective.

Epithelial-mesenchymal transition (EMT) is a key step in transdifferentiation process in solid cancer development. Forthcoming evidence suggest that the stratified program transforms polarized, immotile epithelial cells to migratory mesenchymal cells associated with enhancement of breast cancer stemness, metastasis, and drug resistance. It involves primarily several signaling pathways, such as transforming growth factor-ß (TGF-ß), cadherin, notch, plasminogen activator protein inhibitor, urokinase plasminogen activator, and WNT/beta catenin pathways. However, current understanding on the crosstalk of multisignaling pathways and assemblies of key transcription factors remain to be explored. In this review, we focus on the crosstalk of signal transduction pathways linked to the current therapeutic and drug development strategies. We have also performed the computational modeling on indepth the structure and conformational dynamic studies of regulatory proteins and analyze molecular interactions with their associate factors to understand the complicated process of EMT in breast cancer progression and metastasis. Electrostatic potential surfaces have been analyzed that help in optimization of electrostatic interactions between the protein and its ligand. Therefore, understanding the biological implications underlying the EMT process through molecular biology with biocomputation and structural biology approaches will enable the development of new therapeutic strategies to sensitize tumors to conventional therapy and suppress their metastatic phenotype.

Synthesis of D-Ring Annulated Pyridosteroids from ß-Formyl Enamides and Their Biological Evaluations.

Herein, we report the synthesis of a novel class of substituted androst[17,16- b]pyridines (pyridosteroids) from the reaction of ß-formyl enamides with alkynes in high yields. The optimized reaction protocol was extended to acyclic and cyclic ß-formyl enamides to afford nonsteroidal pyridines. Cell survival assay of all compounds were carried against prostate cancer PC-3 cells wherein 3-hydroxy-5-en-2',3'-dicarbethoxy-androst[17,16- b]pyridine showed the highest cytotoxic activity. Phase contrast microscopy and flow cytometry studies exhibited marked morphological features characteristic of apoptosis in 3-hydroxy-5-en-2',3'-dicarbethoxy-androst[17,16- b]pyridine and abiraterone treated PC-3 cells. The treatment of 3-hydroxy-5-en-2',3'-dicarbethoxy-androst[17,16- b]pyridine induces G2/M phase cell cycle arrest in prostate cancer PC-3 cells. Enhancement of apoptotic inductions of PC-3 cells by 3-hydroxy-5-en-2',3'-dicarbethoxy-androst[17,16- b]pyridine and abiraterone through the activation of caspases-6, -7, and -8 pathways were supported by qRT-PCR. In silico study of the compound 3-hydroxy-5-en-2',3'-dicarbethoxy-androst[17,16- b]pyridine showed stable and promising interaction with the key caspase proteins. Our studies revealed that the pyridosteroid 3-hydroxy-5-en-2',3'-dicarbethoxy-androst[17,16- b]pyridine, bearing pyridine-2,3-dicarbethoxy pharmacophore, facilitated initiation of caspase-8 and activates downstream effectors caspase-6 and caspase-7 and thereby triggering apoptosis of PC-3 cancer cells.

Cytosolic and Transmembrane Protein Extraction Methods of Breast and Ovarian Cancer Cells: A Comparative Study.

Efficient extraction of proteins is a great challenge for numerous downstream proteomic analyses. During the protein extraction procedure, it is critical to maintain the conformational stability, integrity, as well as higher yield of the protein. To do so, 5-different lysis buffers of Tris and HEPES have been used as the primary buffering reagents with variable compositions at different concentrations and pH using human cancer cells. In this study, different protein lysates of human breast cancer cells T47D and MDA-MB-231 and ovarian cancer cell PA-1 were subjected to run SDS-PAGE for separation of proteins based on their molecular size, followed by Coomassie blue, silver staining, and immunoblot assays to compare the extraction yield of total cytoplasmic proteins, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and the integral membrane protein, integrin ß-1. Our results revealed that Tris-based lysis buffer with 50 mM concentration, pH 7.5, is relatively the efficient and reliable protein extraction method for a wide range of MW subcellular markers, cytoplasmic GAPDH and transmembrane integrin ß-1 proteins. We anticipate that this simple and cost-effective protein extraction protocol might be extremely useful across a broad range of subcellular proteins in different biologic samples.

Origins based clinical and molecular complexities of epithelial ovarian cancer.

Ovarian cancer is the most lethal of all common gynaecological malignancies in women worldwide. Ovarian cancer comprises of >15 distinct tumor types and subtypes characterized by histopathological features, environmental and genetic risk factors, precursor lesions and molecular events during oncogenesis. Recent studies on gene signature profiling of different subtypes of ovarian cancer have revealed significant genetic heterogeneity between and within each ovarian cancer histological subtype. Thus, an immense interest have shown towards a more personalized medicine for understanding the clinical and molecular complexities of four major types of epithelial ovarian cancer (serous, endometrioid, clear cell, and mucinous). As such, further in depth studies are needed for identification of molecular signalling network complexities associated with effective prognostication and targeted therapies to prevent or treat metastasis. Therefore, understanding the metastatic potential of primary ovarian cancer and therapeutic interventions against lethal ovarian cancer for the development of personalized therapies is very much indispensable. Consequently, in this review we have updated the key dysregulated genes of four major subtypes of epithelial carcinomas. We have also highlighted the recent advances and current challenges in unravelling the complexities of the origin of tumor as well as genetic heterogeneity of ovarian cancer.

Functionalized graphene oxides for drug loading, release and delivery of poorly water soluble anticancer drug: A comparative study.

In this work, the modification of graphene oxides (GOs) have been done with hydrophilic and biodegradable polymer, polyvinylpyrrolidone (PVP) and other excipient ß -cyclodextrin (ß-CD) through covalent functionalization for efficient loading and compatible release of sparingly water soluble aromatic anticancer drug SN-38 (7-ethyl-10-hydroxy camptothecin). The drug was loaded onto both GO-PVP and GO-ß-CD through the π-π interactions.The release of drug from both the nanocarriers were analyzed in different pH medium of pH 7 (water, neutral medium), pH 5 (acidic buffer) and pH 12 (basic buffer). The loading capacity and the cell killing activity of SN-38 loaded on functionalized GO were investigated comprehensively in human breast cancer cells MCF-7.Our findings shown that the cytotoxicity of SN-38 loaded to the polymer modified GO was comparatively higher than free SN-38. In particular, SN-38 loaded GO-PVP nanocarrier has more cytotoxic effect than GO-ß-CD nanocarrier against MCF-7 cells, indicating that SN-38 loaded GO-PVP nanocarrier can be used as promising material for drug delivery and biological applications.