Prevent Cancer Cell Growth Research Articles

Tyrosine kinase inhibitors in the treatment of leptomeningeal carcinomatosis.

Leptomeningeal carcinomatosis (LMC) is a devastating complication of advanced cancers, such as lung cancer and breast cancer, which is usually indicative of a poor prognosis. The current treatments for LMC include palliative care, with others aiming to prolong survival and relieve neurological symptoms. Traditional treatments for LMC include radiotherapy, systemic chemotherapy, and intrathecal injection. Furthermore, the application of molecularly targeted agents, such as antiepidermal growth factor receptor (anti-EGFR), antihuman epidermal growth factor receptor 2 (anti-HER2), and anti-PD-1 monoclonal antibody, have prolonged the survival of LMC patients. Targeted therapy with tyrosine kinase inhibitors has also been proven to be an effective treatment. Tyrosine kinases can be overactive or expressed at high levels in some cancer cells; therefore, the use of tyrosine kinase inhibitors may prevent the activation of tumor-related pathways, preventing cancer cell growth. The EGFR family are cell surface receptors directly related to tumor occurrence with tyrosine kinase activity; it is the most widely used target for tyrosine kinase inhibitors in the treatment of LMC. In this review, we introduced the clinical manifestation and diagnostic criteria of LMC, clarified the treatment mechanism of tyrosine kinase inhibitors for LMC with mutations in EGFR, HER2, or anaplastic lymphoma kinase, reviewed the current application of various generation tyrosine kinase inhibitors in patients with LMC, and discussed new clinical trials and the future directions of tyrosine kinase inhibitor therapy.

Evaluation of newly synthesized 2-(thiophen-2-yl)-1H-indole derivatives as anticancer agents against HCT-116 cell proliferation via cell cycle arrest and down regulation of miR-25

In the present study, we prepared new sixteen different derivatives. The first series were prepared (methylene)bis(2-(thiophen-2-yl)-1H-indole) derivatives which have (indole and thiophene rings) by excellent yield from the reaction (2 mmol) 2-(thiophen-2-yl)-1H-indole and (1 mmol) from aldehyde. The second series were synthesized (2-(thiophen-2-yl)-1H-indol-3-yl) methyl) aniline derivatives at a relatively low yield from multicomponent reaction of three components 2-(thiophen-2-yl)-1H-indole, N-methylaniline and desired aldehydes. The anticancer effect of the newly synthesized derivatives was determined against different cancers, colon, lung, breast and skin. The counter screening was done against normal Epithelial cells (RPE-1). The effect on cell cycle and mechanisms underlying of the antitumor effect were also studied. All new compounds were initially tested at a single dose of 100 μg/ml against this panel of 5 human tumor cell lines indicated that the compounds under investigation exhibit selective cytotoxicity against HCT-116 cell line and compounds (4g, 4a, 4c) showed potent anticancer activity against HCT-116 cell line with the inhibitory concentration IC50 values were, 7.1±0.07, 10.5± 0.07 and 11.9± 0.05 μΜ/ml respectively. Also, the active derivatives caused cell cycle arrest at the S and G2/M phase with significant(p < 0.0001) increase in the expression levels of tumor suppressors miR-30C, and miR-107 and a tremendous decrease in oncogenic miR-25, IL-6 and C-Myc levels. It is to conclude that the anticancer activity could be through direct interaction with tumor cell DNA like S-phase-dependent chemotherapy drugs. Which can interact with DNA or block DNA synthesis such as doxorubicin, cisplatin, or 5-fluorouracil and which were highly effective in killing the cancer cells. This data ensures the efficiency of the 3 analogues on inducing cell cycle arrest and preventing cancer cell growth. The altered expressions explained the molecular mechanisms through which the newly synthesized analogues exert their anticancer action.

Abstract 1666: A novel sox-based continuous and homogeneous assay for the discovery of inhibitors of inactive and active AKT

Abstract Introduction: The activity of protein kinases plays a critical role in the aberrant activation of oncogenic signaling pathways which can drive tumorigenesis and malignant transformation in cancer. AKT has been shown to be both upregulated and mutated in cancer cells allowing it to serve as a driver of cancer cell growth and progression. Inhibition of AKT activation and activity are both attractive targets for effective cancer drug discovery. Experimental Procedures: We developed continuous, homogeneous assays for unactive AKTs. A peptide substrate, modified with a sulfonamido-oxine fluorophore (Sox), utilizes chelation-enhanced fluorescence to enable a real-time readout of AKT-driven phosphorylation. First, a subset of 30,000 Sox-containing sequences were evaluated for AKT substrate candidates, selecting for assay robustness and specificity. A physiologically relevant peptide substrate was identified and used to develop a kinetic assay to monitor AKT1 activation and activity. Unactive AKT1 was incubated with DOPS/DOPC and PIP3, which mimics the plasma membrane, allowing the PH domain of AKT to bind, leading to a conformational change that enables full activation of AKT by PDK1 and MK2. Upon assay initiation, active AKT phosphorylates the sensor peptide, and the resulting signal is read in kinetic mode using a fluorescence intensity readout. First derivative plots for each progress curve were generated; the slope of the linear regions of each plot, representing acceleration towards a steady-state, were used to determine relative rates of activation for each AKT. Results: We developed a novel assay for AKT activation and substrate phosphorylation utilizing AQT0076, DOPS/DOPC, PIP3, PDK1, and MK2. With a mix of classical AKT inhibitors and allosteric inhibitors that rely on an inactive “PH-in” conformation, we demonstrated inhibition and quantified inhibitor potency of both active “PH-out” AKT activity and inactive “PH-in” AKT activation via dose-response measurements of steady-state rate and rate acceleration, respectively. Conclusions: A robust, homogeneous assay was developed to simultaneously monitor AKT activation and substrate phosphorylation kinetically over time. Through a continuous assay, we captured both steady-state rates and rate acceleration as a function of inhibitor concentration, allowing for accurate quantitation of both classes of AKT inhibitors in a single experimental format. With some inhibitors, we observed potencies that matched reported literature values, while with others we observed marked differences that may reflect a more physiological context that could translate through to higher efficacy in the clinic. This novel assay format provides a new tool that can be used in drug discovery to generate more effective next generation inhibitors of both AKT activation and subsequent substrate phosphorylation to prevent cancer cell growth and progression. Citation Format: Susan Cornell-Kennon, Daniel Urul, Matthew Hakar, Hayley McMahon, Khanh Huynh, Earl May, Erik Schaefer. A novel sox-based continuous and homogeneous assay for the discovery of inhibitors of inactive and active AKT [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1666.

The efficacy of ZnO-NPs prepared via green route against colon and breast cancer cells

This study is an attempt to utilize green tea [GT] extract and pomegranate peel [PP] for the synthesis of zinc oxide nanoparticles. The selected plants are rich in phenols therefore are awaited to successfully synthesize ZnO nanoparticles without the need for an alkylating agent. In addition, these extracts contain various functional groups that confer colloidal stability for nanoparticles and ameliorate their biocompatibility via a one pot synthesis route. X-ray diffraction analysis (XRD), and transmission electron microscopy (TEM) techniques are used to investigate both structural and morphological properties of the obtained nanoparticles [Zn-GT and Zn-PP]. To confirm the presence of functional groups adsorbed on the surface of biogenic-NPs, Fourier transform infrared spectroscopy (FTIR) and thermogravimetric analysis (TGA) were employed. The outcomes demonstrated that only the use of green tea extract was successful in synthesizing zinc oxide from the zinc acetate dihydrate precursor, producing particles with an average size of approximately 25 nm. Anticancer activity and cytotoxicity of the biosynthesized Zn-GT nanoparticles were assessed against human breast cancer [MCF7] and colorectal carcinoma [HCT116] cell lines. The cytotoxicity of ZnO nanoparticles is presented with reference to normal skin [BJ1] cell line subjected to similar concentrations of the NPs. The obtained results verified a discriminative inhibition of both MCF7 and HCT116 cancer cell growth upon using Zn-GT, which completely succeeded in preventing cancer cell growth.

Brassica juncea seeds and seedlings are potential functional foods with diverse active myrosinases

Brassica juncea is an important oilseed and vegetable crop which occupies 90% of the area under mustard cultivation in India. Seeds, seedlings (microgreens), and leaves are a rich in proteins, carbohydrates, minerals, vitamins, and glucosinolates (sinigrin). Sinigrin hydrolysis by myrosinases produces bioactive allyl-isothiocyanate which prevents cancer cell growth, diabetes, hypertension, and neurodegenerative diseases. Myrosinase activity was detected in seeds and all vegetative tissues of seedlings and mature plants. Multiple heterodimeric myrosinases (64 and 65 kDa) were purified from seeds and seedlings using DEAE, hydrophobic interaction, and lectin affinity chromatography. Purified myrosinases were thermostable and had broad pH activity. Seed myrosinases were highly stable at 4 °C retaining >95% activity making them suitable candidates for use in the nutraceutical industry. The inclusion of seeds and microgreens of B. juncea which are rich in sinigrin and myrosinases in a regular diet could help achieve good health and well-being.

In vitro and in silico evaluation of new thieno[2,3-d]pyrimidines as anti-cancer agents and apoptosis inducers targeting VEGFR-2

In this study, new thieno[2,3-d]pyrimidine derivatives that could have potential anticancer activity by inhibiting the VEGFR-2 receptor have been designed, synthesized, and investigated. The thieno[2,3-d]pyrimidine derivatives showed strong in vitro abilities to inhibit VEGFR-2 and to prevent cancer cell growth in two different types of cancer cells, MCF-7 and HepG2. Particularly, compound 22 showed the most potent anti-VEGFR-2 activity with an IC50 value of 0.58 µM. Additionally, compound 22 exhibited good anti-proliferative activity against both MCF-7 and HepG2 cancer cell lines, with IC50 values of 11.32 ± 0.32 and 16.66 ± 1.22 µM, respectively. Further investigations revealed that compound 22 induced cell cycle arrest at the G2/M phase and promoted both early and late apoptosis in the MCF-7 cancer cells. Compound 22 also increased the level of BAX (2.8-fold), and reduced the level of Bcl-2 (2.2-fold), hence increasing the rate of apoptosis. Compound 22 also revealed 2.9-fold and 2.8-fold higher levels of caspase-8 and caspase-9, respectively, in the treated MCF-7 cancer cells compared to the control cell lines. The MD simulations showed that the VEGFR-2-22 complex was structurally and energytically stable over 100 ns, while the MM-GBSA study indicated its stable thermodynamic behavior. The bi-dimensional projection analysis confirmed the proper binding of the VEGFR-2-22 complex, while the DFT studies provided optimized geometry, charge distribution, FMO, ESP, the total density of state, and QTAIM maps of compound 22. Finally, computational ADMET studies were performed to assess the drug development potential of the thieno[2,3-d]pyrimidine derivatives. Overall, this study suggests that compound 22 has the potential as an anticancer lead compound by inhibiting VEGFR-2, which may be a guide for future drug design and development.

Synthesis and Anti-Proliferative Activity of 5-Benzoyl and 5-Benzylhydroxy Derivatives of 3-Amino-2-Arylcarboxamido-Thieno[2-3-b]Pyridines.

3-Amino-2-arylcarboxamido-thieno[2-3-b]pyridines have been previously described as having potent anti-proliferative activity against MDA-MB-231 and HCT116 cancer cell lines. The mechanism by which these molecules prevent cancer cell growth is proposed to be through interfering with phospholipid metabolism via inhibition of PI-PLC, along with other cellular processes. Previously, 5-cinnamyl derivatives of these thieno[2-3-b]pyridines have been shown to have enhanced anti-proliferative activity compared to compounds lacking this moiety, indicating a tethered aromatic ring is important for this western region of the pharmacophore. Herein, we report the synthesis and biological evaluation of a library of 40 novel thieno[2-3-b]pyridine analogues containing shorter benzoyl or secondary benzyl alcohol tethers at the 5-position, in addition to various substituents on the two phenyl rings present on the molecule. Compounds bearing alcohol functionality had improved efficacy compared to their benzoyl counterparts, in addition to a 2-methyl-3-halogen substitution on the 2-arylcarboxamide ring being important for maximising anti-proliferative activity. The most potent molecules 7h and 7i demonstrated IC50 concentrations of 25-50 nM against HCT116 and MDA-MB-231 cells, a similar level of activity as previous thienopyridine compounds bearing cinnamyl moieties, suggesting that these novel derivatives with shorter tethers were able to maintain potent anti-proliferative activity, while allowing for a more concise synthesis.

Apoptotic potential of geranyl acetate in HepG2 liver cancer cells

Natural compounds having apoptotic effects are a new potential source for anti-cancer drugs. Numerous plant phytochemicals have proven anti-cancer properties by inducing programmed cell death (apoptosis). The disease known as cancer is characterized by the uncontrollable growth of some body cells and their spread to other body regions. Worldwide, cancer is a major cause of death. The objective of the current study was to assess apoptotic potential of geranyl acetate on HepG2 cancer cell line. Cell death and cell viability in groups were assessed using the MTT, trypan blue and crystal violet to assess anti-proliferative effect. P53 ELISA was carried out to assess apoptosis. When HepG2 cells were exposed to geranyl acetate they exhibited increased cytotoxicity, decreased viability, proliferation, and increased apoptosis. It is concluded that geranyl acetate has the potential to cause apoptosis via P53 in HepG2 cells. It can also prevent cancer cell growth and proliferation.

Aspergillus niger CJ6 extract with antimicrobial potential promotes in-vitro cytotoxicity and induced apoptosis against MIA PaCa-2 cell line

Nowadays, the increased number of multidrug-resistant strains among pathogens is a severe public health concern and cancer is posing a great threat for humans. These problems should be tackled with the development of novel and broad-spectrum antimicrobials from microbial origin. During the present study, the bioactive secondary metabolites from Aspergillus niger CJ6 were extracted, characterized; their biological properties were evaluated by subjecting them for antimicrobial, antifungal and anticancer activities. The potent isolate Aspergillus niger CJ6 with nucleotide sequence of 959 base pairs showed antagonistic activity against fungal pathogens in dual culture. The chemical profiling of crude ethyl acetate extract indicated the presence of various bioactive molecules belonging to phenolic, hydrocarbons, and phthalate derivative classes. In antimicrobial activity, the crude extract displayed increasing activity with increased concentration; the highest activity observed against Shigella flexneri with 15 ± 1.0, 19 ± 0.5, 20 ± 1.0 and 24 ± 1.0 mm zones of inhibition at 25, 50, 75 and 100 μl concentrations. The MTT assay illustrated deformed cells of MIA PaCa-2 cell line in in-vitro cytotoxic activity; outflow of cell matrix and membrane rupture; the IC50 of 90.78 μg/ml suggested moderate potential of extract to prevent cancer cell growth. The apoptosis/necrosis study by flow cytometer exhibited 8.98 ± 0.85% early and 73 ± 0.7% of late apoptotic population with 3.8 ± 1.1% necrotic cells; only 14.22 ± 0.6% of healthy cells suggested the increased apoptosis inducing capacity of Aspergillus niger CJ6 crude extract. The outcomes of this study persuade further exploration on the identification, purification and development of novel bioactive agents that could help battle fatal diseases in humans.

Targeted Nanodrugs to Destroy the Tumor Extracellular Matrix Barrier for Improving Drug Delivery and Cancer Therapeutic Efficacy.

One of the main reasons why most cancer patients do not respond well to chemotherapy is that drugs cannot accumulate in tumors at an optimal dose, eventually resulting in failure to prevent cancer cell growth. To improve drug delivery efficiency, we engineered a highly efficient tumor-targeted and stroma-breaking nanocarrier by the modification of iron oxide nanoparticles (IONPs) with a tumor-targeting peptide c(RGDyK) and a hyaluronidase (HAase) on the surface. The yielding nanocomplex, c(RGDyK)-HAase-IONP, targeted the tumor by binding integrin αvβ3 and went deeply into the tumors by the degradation of hyaluronic acid (HA), which was highly expressed in the tumor extracellular matrix (ECM). Good biostability and a low pH preferred drug release profile were characterized for c(RGDyK)-HAase-IONP carrying DOX in vitro. c(RGDyK)-HAase-IONP showed an improved tumor-targeting (2.5 times higher) effect after intravenous injection in the MC38 tumor-bearing mice model, as determined by whole-body fluorescence imaging compared to the non-targeted IONPs without HAase. After 5 systemic treatments, c(RGDyK)-HAase-IONP/DOX (5 mg/kg of equivalent dose of DOX) significantly inhibited MC38 tumor growth (22.1 ± 7.4 times relative to the non-treated group). Elevated apoptosis and reduced proliferation in the tumor cell were detected in the c(RGDyK)-HAase-IONP/DOX treated tumors compared to the control groups. Overall, the highly efficient targeted nanocarrier c(RGDyK)-HAase-IONP demonstrated tremendous potency for improving drug delivery and tumor therapy efficacy by targeted degradation of the dense HA barrier in the tumor ECM. We determined that such a tumor stroma-degrading nanosystem was capable of reducing tumor recurrence and drug resistance and could ultimately improve clinical tumor treatment responses.

Design, synthesis, anti-proliferative evaluation, docking, and MD simulation studies of new thieno[2,3-d]pyrimidines targeting VEGFR-2.

In this work, new thieno[2,3-d]pyrimidine-derived compounds possessing potential anticancer activities were designed and synthesized to target VEGFR-2. The thieno[2,3-d]pyrimidine derivatives were tested in vitro for their abilities to inhibit VEGFR-2 and to prevent cancer cell growth in two types of cancer cells, MCF-7 and HepG2. Compound 18 exhibited the strongest anti-VEGFR-2 potential with an IC50 value of 0.084 μM. Additionally, it displayed excellent proliferative effects against MCF-7 and HepG2 cancer cell lines, with IC50 values of 10.17 μM and 24.47 μM, respectively. Further studies revealed that compound 18 induced cell cycle arrest in G2/M phase and promoted apoptosis in MCF-7 cancer cells. Apoptosis was stimulated by compound 18 by increasing BAX (3.6-fold) and decreasing Bcl-2 (3.1-fold). Additionally, compound 18 significantly raised the levels of caspase-8 (2.6-fold) and caspase-9 (5.4-fold). Computational techniques were also used to investigate the VEGFR-2-18 complex at a molecular level. Molecular docking and molecular dynamics simulations were performed to assess the structural and energetic features of the complex. The protein-ligand interaction profiler analysis identified the 3D interactions and binding conformation of the VEGFR-2-18 complex. Essential dynamics (ED) study utilizing principal component analysis (PCA) described the protein dynamics of the VEGFR-2-18 complex at various spatial scales. Bi-dimensional projection analysis confirmed the proper binding of the VEGFR-2-18 complex. In addition, the DFT studies provided insights into the structural and electronic properties of compound 18. Finally, computational ADMET and toxicity studies were conducted to evaluate the potential of the thieno[2,3-d]pyrimidine derivatives for drug development. The results of the study suggested that compound 18 could be a promising anticancer agent that may provide effective treatment options for cancer patients. Furthermore, the computational techniques used in this research provided valuable insights into the molecular interactions of the VEGFR-2-18 complex, which may guide future drug design efforts. Overall, this study highlights the potential of thieno[2,3-d]pyrimidine derivatives as a new class of anticancer agents and provides a foundation for further research in this area.

Equilibria of complexes in the aqueous cobalt(II)–N-(2-hydroxybenzyl)phenylalanine system and their biological activity compared to analogous Schiff base structures

Due to their excellent prospects in biological applications, Schiff bases and their complexes are a source of continuing interest. The present study examines the formation of four cobalt(II) complexes with the reduced Schiff base N-(2-hydroxybenzyl)phenylalanine (PhAlaSal) in alkaline aqueous solution by pH-metry. UV–Vis and ESI–MS studies confirmed the model of proposed species. Kinetic analysis indicated that the single- and bi-ligand cobalt(II) complexes transitioned from octahedral to tetrahedral structures. The Schiff base and its complexes detected under physiological pH were tested for antimicrobial abilities and compared with analogous structures of the Schiff base derivative, N-(2-hydroxybenzyl)alanine (AlaSal). The ability of these structures to influence cell growth was tested on L929 mouse fibroblasts and on cervix and gastric adenocarcinoma cancer cell lines. N-(2-hydroxybenzyl)phenylalanine demonstrates greater antimicrobial efficacy than N-(2-hydroxybenzyl)alanine but also higher cytotoxicity; however, it is nonetheless effective against cancer cells. In turn, AlaSal demonstrates low cytotoxicity for fibroblasts and high cytotoxicity for gastric adenocarcinoma epithelial cells at bacteriostatic concentration for Helicobacter pylori and Candida strains. The presence of these microorganisms in the gastric milieu supports the development of gastritis and gastric cancer; AlaSal therapy may be simultaneously effective against both. Due to their cytotoxicity, Schiff base complexes are not suitable for use against fungal and bacterial infections, but may effectively prevent cancer cell growth. Data availabilityData will be made available on request.

Function and inhibition of Haspin kinase: targeting multiple cancer therapies by antimitosis.

Haploid germ cell-specific nuclear protein kinase (Haspin) is a serine/threonine kinase as an atypical kinase, which is structurally distinct from conventional protein kinases. Functionally, Haspin is involved in important cell cycle progression, particularly in critical mitosis regulating centromeric sister chromatid cohesion during prophase and prometaphase, and subsequently ensuring proper chromosome alignment during metaphase and the normal chromosome segregation during anaphase. However, increasing evidence has demonstrated that Haspin is significantly upregulated in a variety of cancer cells in addition to normal proliferating somatic cells. Its knockdown or small molecule inhibition could prevent cancer cell growth and induce apoptosis by disrupting the regular mitotic progression. Given the specificity of its expressed tissues or cells and the uniqueness of its current known substrate, Haspin can be a promising target against cancer. Consequently, selective synthetic and natural inhibitors of Haspin have been widely developed to determine their inhibitory power for various cancer cells in vivo and in vitro. Here our perspective includes a comprehensive review of the roles and structure of Haspin, its relatively potent and selective inhibitors and Haspin's preliminary studies in a variety of cancers.

F-box protein FBXO41 plays vital role in arsenic trioxide-mediated autophagic death of cancer cells

Arsenic trioxide (ATO), a potent anti-neoplastic drug, is known to prevent cancer cell growth through induction of autophagic cell death. However, importance of cellular factors in ATO-mediated autophagic cell death is poorly understood. In this study, using biochemical and immunofluorescence techniques, we show that F-box protein FBXO41 plays a critical role in anti-proliferative activity of ATO. Our study reveals the importance of FBXO41 in induction of autophagic death of cancer cells by ATO. Further, we show that the autophagic cell death induced by FBXO41 is distinct and independent of apoptosis and necrosis, showing that FBXO41 may play vital role in inducing autophagic death of apoptosis resistant cancer cells. Overall, our study elucidates the importance of FBXO41 in ATO induced autophagic cell death to prevent cancer progression, which could be explored to develop promising cancer therapeutic strategy.

An Analysis of Health Aid s of Apple

Evidence indicates that diet consisting fruits &amp; vegetations may inferior jeopardy of chronic illnesses including disease of heart &amp; cancer, &amp; phytochemicals present in fruits &amp; vegetations, such as phenolics, flavonoids, &amp; carotenoids, may play a significant part in lowering jeopardy of chronic disease. Apple is popular fruit which is rich in phytochemicals, &amp; epidemiological studies have linked apple intake to lower jeopardy of some malignancies, cardiacdisease, asthma, &amp; diabetes. Apples have shown in laboratory to have high antioxidant activity, prevent cancer cell growth, reduce lipid oxidation, &amp; lower cholesterol. Apples are high in phytochemicals such as quercetin, catechin, phloridzin, &amp; chlorogenic acid, which are all powerful antioxidants. phytochemical content of apples varies significantly across various kinds, &amp; re are also minor variations in phytochemicals as fruit matures &amp; ripens. Apple phytochemicals are little to be affected by storage, but y are significantly affected by processing. While re is a lot of data out re, re hasn't a comprehensive assessment of health profits of apples &amp; ir phytochemicals. goal of this article is to examine majorcurrent research on apple phytochemicals, phytochemical bioavailability, &amp; antioxidant activity, along with impacts of variety, ripening, storing, &amp; processing on apple phytochemicals.

Current Status of the Use of Multifunctional Enzymes as Anti-Cancer Drug Targets.

Fighting cancer is one of the major challenges of the 21st century. Among recently proposed treatments, molecular-targeted therapies are attracting particular attention. The potential targets of such therapies include a group of enzymes that possess the capability to catalyze at least two different reactions, so-called multifunctional enzymes. The features of such enzymes can be used to good advantage in the development of potent selective inhibitors. This review discusses the potential of multifunctional enzymes as anti-cancer drug targets along with the current status of research into four enzymes which by their inhibition have already demonstrated promising anti-cancer effects in vivo, in vitro, or both. These are PFK-2/FBPase-2 (involved in glucose homeostasis), ATIC (involved in purine biosynthesis), LTA4H (involved in the inflammation process) and Jmjd6 (involved in histone and non-histone posttranslational modifications). Currently, only LTA4H and PFK-2/FBPase-2 have inhibitors in active clinical development. However, there are several studies proposing potential inhibitors targeting these four enzymes that, when used alone or in association with other drugs, may provide new alternatives for preventing cancer cell growth and proliferation and increasing the life expectancy of patients.

Nanotechnology in Bladder Cancer: Diagnosis and Treatment.

Simple SummaryBladder cancer (BC) is the fourth most common cancer among men and the tenth most common cancer among women. Since the overall prognosis for BC has not changed in the last 30 years, there is a compelling medical need to develop new diagnostic and therapeutic approaches. Nanotechnology has been extensively developed for cancer management, including cancer diagnosis, detection, and treatment. Several nanoparticles (NP) can be used in in vitro cancer diagnostics, in vivo imaging enhancement, and drug loading techniques. In this review, we examine the current state of nanotechnology in the diagnosis and treatment of bladder cancer. We investigated the function of metal NPs, polymeric NPs, liposomes, and exosomes accompanied therapeutic agents for BC therapy, and then focused on the potential of nanotechnology to improve conventional approaches in sensing.Bladder cancer (BC) is the second most common cancer of the urinary tract in men and the fourth most common cancer in women, and its incidence rises with age. There are many conventional methods for diagnosis and treatment of BC. There are some current biomarkers and clinical tests for the diagnosis and treatment of BC. For example, radiotherapy combined with chemotherapy and surgical, but residual tumor cells mostly cause tumor recurrence. In addition, chemotherapy after transurethral resection causes high side effects, and lack of selectivity, and low sensitivity in sensing. Therefore, it is essential to improve new procedures for the diagnosis and treatment of BC. Nanotechnology has recently sparked an interest in a variety of areas, including medicine, chemistry, physics, and biology. Nanoparticles (NP) have been used in tumor therapies as appropriate tools for enhancing drug delivery efficacy and enabling therapeutic performance. It is noteworthy, nanomaterial could be reduced the limitation of conventional cancer diagnosis and treatments. Since, the major disadvantages of therapeutic drugs are their insolubility in an aqueous solvent, for instance, paclitaxel (PTX) is one of the important therapeutic agents utilized to treating BC, due to its ability to prevent cancer cell growth. However, its major problem is the poor solubility, which has confirmed to be a challenge when improving stable formulations for BC treatment. In order to reduce this challenge, anti-cancer drugs can be loaded into NPs that can improve water solubility. In our review, we state several nanosystem, which can effective and useful for the diagnosis, treatment of BC. We investigate the function of metal NPs, polymeric NPs, liposomes, and exosomes accompanied therapeutic agents for BC Therapy, and then focused on the potential of nanotechnology to improve conventional approaches in sensing.

Abstract 2652: Adjuvant therapeutic potential of hypothermia in the treatment of glioblastoma: An in vitro study

Abstract Glioblastoma is a particularly aggressive and infiltrative brain tumor with an annual incidence of three per 100,000 adults worldwide. Despite multimodal treatments, associating surgical resection with combined radiotherapy and temozolomide-based chemotherapy [1], prognosis remains poor. Median survival is only 14 to 16 months because of tumor recurring in the resection margins in over 90% of patients, due to the activation of residual glioblastoma cells. Hence, there is a need for developing novel therapies that improve survival outcome. To handle this issue, we propose therapeutic hypothermia as an adjuvant treatment, to place tumor cells at the resection margin in a dormant state. The aim of our study is to evaluate the adjuvant therapeutic potential of moderate hypothermia by investigating in vitro its ability to prevent cancer cell growth. We previously published results demonstrating that continuous moderate hypothermia at 28 °C is able to significantly inhibit both cell proliferation and migration [2]. We performed in vitro experiments on four glioblastoma cell lines with different p53 status and various growth rates: A-172, U-251 MG, U-87 MG, and T98G. To study the adjuvant potential of moderate hypothermia, we investigated its inhibitory effects on the proliferation of glioblastoma cells exposed to different conditions. First, we studied the impact of different sequences in which cells were successively placed in hypothermic conditions then rewarmed to 37 °C. On the other hand, we compared the inhibitory effects of moderate hypothermia with current chemotherapy protocols. Finally, we investigated the therapeutic potential of combining chemotherapy with hypothermia. Here, we showed that moderate hypothermia significantly inhibited glioblastoma cell proliferation even after rewarming to 37 °C, with a significant influence of hypothermic preconditioning duration. In addition, moderate hypothermia reduced cell proliferation far more than chemotherapy alone, with inhibitory effects up to eight times higher for chemoresistant cell lines. Finally, combining hypothermia with chemotherapy further reduced proliferation, with more than 95% inhibition even after returning glioblastoma cells to 37 °C. Our results showed that glioblastoma cell proliferation was not fully restored upon returning to 37 °C, suggesting that the effects of moderate hypothermia on cell growth are not limited to direct conditioning, which is important for clinical applications. We also demonstrated that responses to moderate hypothermia were similar for all four glioblastoma cell lines whereas they presented different levels of sensitivity to chemotherapy, depending on their p53 status. Moreover, combining both therapeutic approaches significantly improved glioblastoma cell sensitivity to treatment for all cell lines, regardless of their p53 status. Finally, these results showed that moderate hypothermia has the potential to reduce inter-patient variability of treatment efficiency, and thus appears to be a relevant adjuvant therapy for use when treating glioblastoma patients. [1] R. Stupp et al., "Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival⋯", Lancet Oncol., 2009. [2] C. Fulbert et al., "Moderate hypothermia inhibits both proliferation and migration of human glioblastoma cells", J. Neurooncol., 2019. Citation Format: Clémentine Fulbert, Christophe Gaude, Stéphan Chabardès, David Ratel. Adjuvant therapeutic potential of hypothermia in the treatment of glioblastoma: An in vitro study [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2652.

A Novel Approach to Prevent and Restrict Early Stages of Cancer Cell Growth Using a Combination of Moringa and Sesame in a Drosophila Model

Cancer is a highly prevalent disease with many causes but no cure; here, we examined the efficacy of the naturally anti-inflammatory moringa and sesame plants to prevent or restrict cancer cell growth in Drosophila melanogaster. In our previous work, we showed that sesame and moringa individually repressed eye tumor formation in D. melanogaster. In this work, we studied combinations of moringa and sesame at different proportions to compare their effects in preventing cancer cell growth. We studied D. melanogaster eye tumors which allowed easy detection of the phenotypes with simple microscopes. As we increased the concentration of sesame and moringa in the mixture, the cancer symptoms improved. We showed that a diet consisting of a combination of 10% sesame and 15% moringa can be used to effectively prevent visible tumor growth in the D. melanogaster eye, and the endpoints were close to those of healthy, wild-type flies. This data showed improved tumor growth compared to the treatments used individually. We extended the study to restrict early stages of cancer using these treatments. Progeny of Gal4-Ret cross at four different stages of the lifecycle were treated with experimental food and compared to control sample flies. Our study showed this combination of Moringa and Sesame treatments during the second instar or third instar larvae could restrict the cancer cells growth. Therefore, we concluded that a combination of 15% moringa and 10% sesame could prevent cancer and restrict early stages of cancer growth in this specific model of cancer using D. melanogaster.

Adjuvant bisphosphonate therapy in early-stage breast cancer-Treating the soil to kill the seed.

Bisphosphonates alter the tumor microenvironment, possibly preventing cancer cell growth in the bone. Analyses of data from numerous clinical trials and a large individual patient-level data meta-analysis have suggested an anti-tumor effect for bisphosphonates in patients with early-stage breast cancer who are postmenopausal. The absolute benefit from the use of bisphosphonates on breast cancer-related mortality reduction mirrors that seen with the use of anthracycline-based chemotherapy versus a first-generation chemotherapy regimen (CMF). In this review, we discuss the evidence base for the use of adjuvant bisphosphonates in early-stage breast cancer and provide recommendations for clinical use.