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In the present study, extracts from 10 Ganoderma spp. isolates were tested for their cytotoxic effects on various human cancer cell lines. The MTT assay was used to quantify the cell viability. Fluorescence microscopy and flow cytometry demonstrated apoptosis in the treated cell lines. The antibacterial efficacy of the extracts was examined against different gram-positive and negative bacteria. The ethyl acetate extract of strain PTCC 6009 was the most effective cytotoxic agent against MDA-MB-231 cell line, with an IC50 of 314.88 µg/mL. Cells incubated with the IC50 dose of the ethyl acetate extract of strain PTCC 6009 showed percentages of early and late apoptosis at 24 h, with values of 43.6% and 2.3%, respectively. The methanol extract of strain PTCC 6001 (at concentration of 250 mg/mL) demonstrated antibacterial activity against Bacillus subtilis (PTCC 1715) with an inhibition zone of 21.28 mm. These findings indicate the potential therapeutic properties of isolated Ganoderma strains for further pharmacological studies. [ABSTRACT FROM AUTHOR]

Golden chamomile (Matricaria aurea) is widely distributed in Europe and Asia and is commonly used as an alternative to M. chamomilla in traditional medicine in some countries. This review aimed to summarize the reports on the ethnomedicinal uses, phytochemical content, biological, and pharmacological activities of M. aurea. Additionally, a brief mention of the biological activities of M. chamomilla was also included. The literature research was conducted using authentic search engines, including Web of Science, Google Scholar, Pub Med, and Scopus, without time restrictions with keywords such as Matricaria genus, Matricaria aurea, essential oil, phytochemical, biological, and pharmacological activity. Studies on phytochemicals and biological properties were mainly conducted in countries such as Tunisia, Saudi Arabia, and Iran. The chemical composition of essential oil was found to vary depending on the geographical zone of the plant collection site. Sesquiterpenes such as bisabolol oxide, α-bisabolol, and farnesene were identified as common constituents of the essential oil. Phenolic and flavonoid compounds such as chlorogenic acid, ferulic acid, apigenin, and luteolin were reported. Ethnopharmacological studies have shown that the plant was used for the treatment of abdominal pain, flatulence, colds, flu, inflammation, cough, asthma, and insomnia. Additionally, M. aurea has demonstrated antioxidant, antibacterial, cytotoxic, antidiabetic, and anti-inflammatory activities. In conclusion, biological and pharmacological effects of M. aurea and M. chamomilla have many similarities. This supports the idea that M. aurea could be used as an alternative to M. chamomilla. However, further investigations on the possible mechanisms of action and adverse effects of M. aurea are suggested.

Benzothiazole alkaloids are a class of rare heterocyclic alkaloids with unique structures and exhibit a wide range of biological activities. So, the aim of this work is to investigate structural diversity‐guided N‐S heterocyclic derivatives based on natural benzothiazole alkaloids as potential cytotoxic agents. Three series of novel benzothiazole derivatives, including 22 compounds, were designed and synthesized using pharmacophore hybridization, and their in vitro cytotoxic activities against Huh‐7 and A875 were fully evaluated. The results indicated that some of these benzothiazole derivatives had significantly good cytotoxic activities against two tested cell lines compared with the positive control 5‐fluorouracil, and other compounds 3f–3i displayed good selectivity between A875 and Huh‐7 cell lines, which might be used as promising lead molecule for discovery of novel benzothiazole‐type cytotoxic agents. [ABSTRACT FROM AUTHOR]

Golden chamomile (Matricaria aurea) is widely distributed in Europe and Asia and is commonly used as an alternative to M. chamomilla in traditional medicine in some countries. This review aimed to summarize the reports on the ethnomedicinal uses, phytochemical content, biological, and pharmacological activities of M. aurea. Additionally, a brief mention of the biological activities of M. chamomilla was also included. The literature research was conducted using authentic search engines, including Web of Science, Google Scholar, Pub Med, and Scopus, without time restrictions with keywords such as Matricaria genus, Matricaria aurea, essential oil, phytochemical, biological, and pharmacological activity. Studies on phytochemicals and biological properties were mainly conducted in countries such as Tunisia, Saudi Arabia, and Iran. The chemical composition of essential oil was found to vary depending on the geographical zone of the plant collection site. Sesquiterpenes such as bisabolol oxide, a-bisabolol, and farnesene were identified as common constituents of the essential oil. Phenolic and flavonoid compounds such as chlorogenic acid, ferulic acid, apigenin, and luteolin were reported. Ethnopharmacological studies have shown that the plant was used for the treatment of abdominal pain, flatulence, colds, flu, inflammation, cough, asthma, and insomnia. Additionally, M. aurea has demonstrated antioxidant, antibacterial, cytotoxic, antidiabetic, and anti-inflammatory activities. In conclusion, biological and pharmacological effects of M. aurea and M. chamomilla have many similarities. This supports the idea that M. aurea could be used as an alternative to M. chamomilla. However, further investigations on the possible mechanisms of action and adverse effects of M. aurea are suggested. [ABSTRACT FROM AUTHOR]

Introduction: Cinnamic acid is a privileged scaffold for the design of biologically active compounds with putative anticancer potential, following different synthetic methodologies and procedures. Since there is a need for the production of potent anticancer, cinnamate moiety can significantly contribute in the design of new and more active anticancer agents. Areas covered: In this review, the authors provide a review on the synthetic approaches for the discovery of cinnamic acid derivatives with anticancer potential. Results from molecular simulations, hybridization, and chemical derivatization along with biological experiments in vitro and structural activity relationships are given, described, and discussed by the authors. Information for the mechanism of action is taken from original literature sources. Expert opinion: The authors suggest that (i) numerous areas of biology-pharmacology need to be considered: selectivity, in vivo studies, toxicity and drug-likeness, the mechanism of action in animals and humans, development of more efficient assays for various cancer types; (ii) hybridization techniques outbalance in the discovery and production of compounds with higher activity and greater selectivity; (iii) repositioning offers new anticancer cinnamic agents. [ABSTRACT FROM AUTHOR]

AbstractStreptomyces are very important Gram-positive filamentous bacteria because they can produce many beneficial secondary metabolites with various biological activities. The study aims to isolate and identify novel Streptomyces strains from terrestrial habitats in the United Arab Emirates (UAE) with antimicrobial and cytotoxic properties. The antimicrobial efficacy was assessed using the disk and well susceptibility methods. Crude ethyl acetate extracts of active-producing strains were used to determine the antimicrobial activity by minimum inhibitory concentration (MIC) against E. coli, S. aureus, C. albicans, S. cerevisiae, B. subtilis, and E. coli-ESBL (extended-spectrum Beta-Lactamase), and cytotoxic properties against HeLa cells by MTT assay and DAPI staining. The novelty of the strains was determined by sequencing the 16S rRNA fragment. Results showed that antimicrobial activity was observed for CSK1, CSK3, CSW2, CSU1, CSU2, and CSG1 strains, with zones of inhibition ranging between 16 and 35 mm. Minimum inhibitory concentrations of ethyl acetate extracts ranged from 0.21 to 12.17 µg/mL, with the highest inhibitory effect against S. aureus ranging between 0.21 and 0.29 µg/mL. Some strains (CSK3, CSW2, CSU1 and CSG1) also displayed cytotoxic activity against the HeLa cancer cell line with IC50 values ranging between 3.46 and 9.74 µg/µL, and apparent DNA fragmentation and chromatin condensation. This study indicates that Streptomyces sp. strains isolated from different soil habitats in the UAE can produce antimicrobial compounds that can treat microbial infections. In addition, some strains’ cytotoxicity suggests that they are producing bioactive compounds that can lead to drug discovery.

Simple Summary: This review summarizes the present knowledge of cytotoxic agents and protective systems against these damaging substances in tumors. In tumor cells, enhanced levels of cytotoxic agents are usually counteracted by an overexpression of protective mechanisms. In this manner, tumor cells can even survive therapeutically induced stress situations. Tumor cells also affect immune cells and other cells in their close neighborhood in such a way that cells in this tumor microenvironment change their properties and promote tumor progression. Numerous examples are given for how the disturbed balance between inflammation-associated cytotoxic agents and antagonizing principles is related to tumor growth, tumor cell invasion, and metastasis. A thorough knowledge of these mechanisms is mandatory for the implementation of novel therapeutic approaches against cancers. Chronic inflammatory processes are related to all stages of tumorigenesis. As inflammation is closely associated with the activation and release of different cytotoxic agents, the interplay between cytotoxic agents and antagonizing principles is highlighted in this review to address the question of how tumor cells overcome the enhanced values of cytotoxic agents in tumors. In tumor cells, the enhanced formation of mitochondrial-derived reactive species and elevated values of iron ions and free heme are antagonized by an overexpression of enzymes and proteins, contributing to the antioxidative defense and maintenance of redox homeostasis. Through these mechanisms, tumor cells can even survive additional stress caused by radio- and chemotherapy. Through the secretion of active agents from tumor cells, immune cells are suppressed in the tumor microenvironment and an enhanced formation of extracellular matrix components is induced. Different oxidant- and protease-based cytotoxic agents are involved in tumor-mediated immunosuppression, tumor growth, tumor cell invasion, and metastasis. Considering the special metabolic conditions in tumors, the main focus here was directed on the disturbed balance between the cytotoxic agents and protective mechanisms in late-stage tumors. This knowledge is mandatory for the implementation of novel anti-cancerous therapeutic approaches. [ABSTRACT FROM AUTHOR]

Streptomyces are very important Gram-positive filamentous bacteria because they can produce many beneficial secondary metabolites with various biological activities. The study aims to isolate and identify novel Streptomyces strains from terrestrial habitats in the United Arab Emirates (UAE) with antimicrobial and cytotoxic properties. The antimicrobial efficacy was assessed using the disk and well susceptibility methods. Crude ethyl acetate extracts of active-producing strains were used to determine the antimicrobial activity by minimum inhibitory concentration (MIC) against E. coli, S. aureus, C. albicans, S. cerevisiae, B. subtilis, and E. coli-ESBL (extended-spectrum Beta-Lactamase), and cytotoxic properties against HeLa cells by MTT assay and DAPI staining. The novelty of the strains was determined by sequencing the 16S rRNA fragment. Results showed that antimicrobial activity was observed for CSK1, CSK3, CSW2, CSU1, CSU2, and CSG1 strains, with zones of inhibition ranging between 16 and 35 mm. Minimum inhibitory concentrations of ethyl acetate extracts ranged from 0.21 to 12.17 µg/mL, with the highest inhibitory effect against S. aureus ranging between 0.21 and 0.29 µg/mL. Some strains (CSK3, CSW2, CSU1 and CSG1) also displayed cytotoxic activity against the HeLa cancer cell line with IC50 values ranging between 3.46 and 9.74 µg/µL, and apparent DNA fragmentation and chromatin condensation. This study indicates that Streptomyces sp. strains isolated from different soil habitats in the UAE can produce antimicrobial compounds that can treat microbial infections. In addition, some strains' cytotoxicity suggests that they are producing bioactive compounds that can lead to drug discovery. [ABSTRACT FROM AUTHOR]

With the expanding use of Platins and Taxanes for cancer patients, a highly concerning threat is observed in the form of Hypersensitivity reactions. To reduce hypersensitivity reactions, different desensitization protocols are formed. The prevalence of hypersensitivity to carboplatin ranges from 1-27%, oxaliplatin 1-19%, cisplatin 5-20%, and docetaxel 10-20%. Even though the hypersensitivity reactions following the administration of oxaliplatin may be less severe than carboplatin hypersensitivity reactions but extremely life-threatening reactions have been observed also. Some patients, allergic to oxaliplatin show uncharacteristic hypersensitivity signs such as chills, fever, and abdominal and/or extreme chest pain. Symptoms followed by Taxanes induced hypersensitivity reactions are flushing, pruritus, and skin rashes to more life- threatening features like dyspnea, hypotension, angioedema, and occurrence generalized pale red bumps on the skin which is also called as urticarial. Numerous preventive methods have been develop to avoid hypersensitivity reactions and the most effective technique so far is the rapid drug desensitization. It allows re-exposure to the culprit drug safely and effectively. Drug desensitization is a whole set of techniques or process by which an offender drug is introduced in the system of a patient following a cycle of very calculated dose augmentation, in a way that the total administered dose is equal to the actual targ et dose of the drug. Introduced protocols result in better outcomes as expected and now used widely throughout hospitals accordingly. [ABSTRACT FROM AUTHOR]

• HBV reactivation is a severe complication in hepatitis B patients treated with rituximab • In our cohort, many patients were not screened correctly for HBV serology at rituximab initiation • Lack of screening and antiviral prophylaxis resulted in HBV reactivation in a couple of patients • Our findings could be used to raise awareness among all medical specialties Patients with chronic or resolved hepatitis B are at risk of hepatitis B reactivation (HBVr) when treated with high-risk immunosuppressive therapy such as rituximab. Therefore, international guidelines recommend HBV screening prior to rituximab treatment and subsequent antiviral prophylaxis among patients with a (resolved) infection. In this study, we evaluated the adherence to those recommendations. This is a retrospective multicentre study including patients treated with rituximab between 2000-2021. Performance of correct screening was assessed, defined as the measurement of hepatitis B surface antigen (HBsAg) and hepatitis B core antibodies (anti-HBc). Next, initiation of antiviral prophylaxis and HBVr rate among patients with a chronic or resolved HBV infection was studied. We enrolled 3,176 patients of whom 1,448 (46%) were screened correctly. Screening rates differed significantly between academic and non-academic hospitals; respectively 65% vs 32% (p<0.001). In addition, screening rates differed across specialties and improved throughout the years; from 32% before 2012 to 75% after 2020 among academic prescribers, versus 1% to 60% among non-academic prescribers (both p<0.001). Antiviral prophylaxis was initiated in 58% vs 36% of the patients with a chronic or resolved HBV infection. Seven patients experienced HBVr, including one fatal liver decompensation. Many patients treated with rituximab were not correctly screened for HBV infection and antiviral prophylaxis was often not initiated. Although screening rates improved over time, rates remain suboptimal. With the increasing number of indications for rituximab and other immunosuppressive agents these findings could raise awareness among all medical specialties prescribing these agents. [ABSTRACT FROM AUTHOR]

Silk fibroin has been widely used in biological fields due to its biocompatibility, mechanical properties, biodegradability, and safety. Recently, silk fibroin as a drug carrier was developed rapidly and achieved remarkable progress in cancer treatment. The silk fibroin-based delivery system could effectively kill tumor cells without significant side effects and drug resistance. However, few studies have been reported on silk fibroin delivery systems for antitumor therapy. The advancement of silk fibroin-based drug delivery systems research and its applications in cancer therapy are highlighted in this study. The properties, applications, private opinions, and future prospects of silk fibroin carriers are discussed to understand better the development of anti-cancer drug delivery systems, which may also contribute to advancing silk fibroin innovation. [ABSTRACT FROM AUTHOR]

Cyclin-dependent kinase 9 (CDK9) plays a critical role in transcriptional elongation, through which short-lived antiapoptotic proteins are overexpressed and make cancer cells resistant to apoptosis. Therefore, CDK9 inhibition depletes antiapoptotic proteins, which in turn leads to the reinstatement of apoptosis in cancer cells. Twenty-seven compounds were synthesized, and their CDK9 inhibitory and cytotoxic activities were evaluated. Compounds 7, 9, and 25 were the most potent CDK9 inhibitors, with IC50 values of 0.115, 0.131, and 0.142 μM, respectively. The binding modes of these molecules were studied via molecular docking, which shows that they occupy the adenosine triphosphate binding site of CDK9. Of these three molecules, compound 25 shows good drug-like properties, as it does not violate Lipinski's rule of five. In addition, this molecule shows promising ligand and lipophilic efficiency values and is an ideal candidate for further optimization. [ABSTRACT FROM AUTHOR]

The purpose of this study was to assess surgical outcomes of salvage surgery for clinical stage IV non-small cell lung cancer. A total of 14 patients who underwent lung resection following systemic therapy between 2010 and 2022 were included in this study. Systemic therapy prior to surgery included agents including epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in 8 patients and non-TKI agents in 6 (chemotherapy alone: 4, chemotherapy plus immune checkpoint inhibitors [ICIs]: 2). During a median follow-up of 5.2 years, the EGFR-TKI group showed a favourable 5-year overall survival of 83%; however, it was due to treatment after relapse, and there were no 4-year relapse-free survivors. The non-EGFR-TKI group showed a 5-year relapse-free survival of 33%, and 2 patients have survived more than 3 years without any relapse and further treatment. When considering the role of surgery in multimodal treatment for initial c-stage IV NSCLC, salvage surgery following non-TKI therapy (chemotherapy with or without ICI) can be regarded as genuine salvage surgery., (© The Author(s) 2025. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

[Display omitted] It is a major concern to treat cancer successfully, due to the distinctive pathophysiology of cancer cells and the gradual manifestation of resistance. Specific action, adverse effects and development of resistance has prompted the urgent requirement of exploring alternative anti-tumour treatment therapies. The naturally derived microbial toxins as a therapy against cancer cells are a promisingly new dimension. Various important microbial toxins such as Diphtheria toxin, Vibrio cholera toxin, Aflatoxin, Patulin, Cryptophycin-55, Chlorella are derived from several bacterial, fungal and algal species. These agents act on different biotargets such as inhibition of protein synthesis, reduction in cell growth, regulation of cell cycle and many cellular processes. Bacterial toxins produce actions primarily by targeting protein moieties and some immunomodulation and few acts through DNA. Fungal toxins appear to have more DNA damaging activity and affect the cell cycle. Algal toxins produce alteration in mitochondrial phosphorylation. In conclusion, microbial toxins and their metabolites appear to have a great potential to provide a promising option for the treatment and management to combat cancer. [ABSTRACT FROM AUTHOR]

Herein we report the mild synthesis of 15 phosphonocinnamic esters by means of a solvent-free mechanically activated Horner-Wadsworth-Emmons (HWE) olefination, in regular to excellent yields (13–99%), from tetraethyl methylenediphosphonate, an aromatic or aliphatic aldehyde and potassium tert-butoxide, using 5 min of mortar and pestle grinding. Potassium tert-butoxide acts as a base and liquid-assisting grinding agent. All isolated products were fully characterized as (E)-isomers through NMR spectroscopy. Furthermore, among the synthesized compounds diethyl (E)-2-(4-methoxyphenyl)vinylphosphonate 1 was discovered as an interesting cytotoxic agent inhibiting growth of two breast cancer cell lines (MDA-MB-453, IC50 = 79 µg/mL and MCF-7 IC50 = 64 µg/mL). To the best of our knowledge, this is the first report of mechanically activated HWE reaction for the synthesis of α, β-unsaturated phosphonates and the first time some of them have been assessed as cytotoxic agents on breast cancer cell lines. In conclusion, the fast and operationally simple synthesis of (E)-phosphonocinnamic esters afforded new promising cytotoxic agents in regular to excellent yields in very short reaction times. [ABSTRACT FROM AUTHOR]

Heterocyclic nucleus is vital in medicinal chemistry and has allured significant attention in chemotherapeutic domain. Oxadiazole, a five-membered nitrogen–oxygen-containing heterocyclic core has remarkable anticancer activity. Mechanism associated in defeating tumor corresponds with inhibiting various enzymes and growth factors. Considering the importance of oxadiazole and its derivatives in this panic issue worldwide, this review has discussed research carried out from last 7 years and also their future outlook in drug development as antineoplastic agents. The objective of this review is to emphasize on anticancer activity of 1,3,4-oxadiazole and 1,2,4-oxadiazole derivatives. The precised features and framework of each research topic is introduced for helping the readers in understanding the perspective of the context in better way. [ABSTRACT FROM AUTHOR]

ABSTRACT The wound healing assay is a simple and inexpensive method that allows researchers to experimentally mimic cell growth and migration leading to wound healing. In this assay, a wound is created on a monolayer of cultured mammalian cells and cell migration is monitored. Micrographs are captured at regular intervals during the duration of the experiment. These microscopy images are analyzed to compare cell migration and wound closure under different conditions. Introduction of different cytotoxic treatments into a wound healing assay can provide information as to whether a particular drug or compound of interest has the ability to affect cell migration. This type of analysis is important when assessing the ability of a particular cancer cell line to display invasive and metastatic behaviors. One of the challenges of this assay is to create the original wound in a way that is consistent across plates or treatments, facilitating comparisons across experimental groups. This is a particular challenge when using the wound healing assay in the context of an undergraduate biology class to expose students to a distinct form of mammalian cell culture and help them apply scientific knowledge and research skills. We found an easy way to overcome this obstacle by using ibidi plates. In this article, we provide a simple protocol to use ibidi plates and HeLa cells to set up wound healing assays. This laboratory exercise allows undergraduate students to utilize different skills developed through cell culture experience, such as growing, treating, and imaging mammalian cells.

Cancer is a disorder that rigorously affects the human population worldwide. There is a steady demand for new remedies to both treat and prevent this life-threatening sickness due to toxicities, drug resistance and therapeutic failures in current conventional therapies. Researchers around the world are drawing their attention towards compounds of natural origin. For decades, human beings have been using the flora of the world as a source of cancer chemotherapeutic agents. Currently, clinically approved anticancer compounds are vincristine, vinblastine, taxanes, and podophyllotoxin, all of which come from natural sources. With the triumph of these compounds that have been developed into staple drug products for most cancer therapies, new technologies are now appearing to search for novel biomolecules with anticancer activities. Ellipticine, camptothecin, combretastatin, curcumin, homoharringtonine and others are plant derived bioactive phytocompounds with potential anticancer properties. Researchers have improved the field further through the use of advanced analytical chemistry and computational tools of analysis. The investigation of new strategies for administration such as nanotechnology may enable the development of the phytocompounds as drug products. These technologies have enhanced the anticancer potential of plant-derived drugs with the aim of site-directed drug delivery, enhanced bioavailability, and reduced toxicity. This review discusses mechanistic insights into anticancer compounds of natural origins and their structural activity relationships that make them targets for anticancer treatments. [ABSTRACT FROM AUTHOR]

Antibody drug conjugates (ADCs) normally compose of a humanized antibody and small molecular drug via a chemical linker. After decades of preclinical and clinical studies, a series of ADCs have been widely used for treating specific tumor types in the clinic such as brentuximab vedotin (Adcetris®) for relapsed Hodgkin's lymphoma and systemic anaplastic large cell lymphoma, gemtuzumab ozogamicin (Mylotarg®) for acute myeloid leukemia, ado-trastuzumab emtansine (Kadcyla®) for HER2-positive metastatic breast cancer, inotuzumab ozogamicin (Besponsa®) and most recently polatuzumab vedotin-piiq (Polivy®) for B cell malignancies. More than eighty ADCs have been investigated in different clinical stages from approximately six hundred clinical trials to date. This review summarizes the key elements of ADCs and highlights recent advances of ADCs, as well as important lessons learned from clinical data, and future directions.

Lack of advancement in detection of abnormal liver cells is a major drawback in hepatocellular carcinoma (HCC) that could results in late diagnosis. This study aims to discriminate the malignant cells from the normal counterparts, and apoptotic cells from viable cells using a microfluidic dielectrophoresis (DEP)-based technology. The discrimination of the viable and non-viable HCC cells was conducted upon treatment with plant-based cytotoxic agent konjac glucomannan (KGM). DEP analyses of human normal liver (WRL68) cells showed slight positive-DEP effect while liver cancer (HepG2) cells was highly negative. This broad dielectric difference is due to the tumorigenic alterations in HepG2 cells. Exposure to cytotoxic agents showed a significant shift from negative-DEP to positive-DEP, indicating apoptosis-induced reduction in membrane negativity. The results indicate the feasibility of DEP method in cancer screening.

Cancer refers to a collection of diseases that have abnormal cell growth as their hallmark. This inability of cytotoxic agents to distinguish between rapidly dividing healthy cells and rapidly multiplying cancerous cells produces the most notorious adverse effects of cytotoxic anticancer agents. As an essential tool in nanotechnology, nanoemulsions have therapeutic and clinical applications. Currently, nanoemulsions are considered to be one of the most feasible nano-carriers for delivering lipophilic antineoplastic agents with targeted delivery. In addition to solving water-solubilization issues, these formulations deliver specific targeting to cancer cells and might even be developed to overcome multi-drug resistance. Nanoemulsions overcome the problems associated with conventional drug delivery systems, such as low bioavailability and noncompliance. A review of nanoemulsion in cancer therapeutics is presented here to shed light on the current position of this technology. [ABSTRACT FROM AUTHOR]

Introduction: Previous prospective studies suggest that the sequential use of cytotoxic agents, such as oxaliplatin, in patients with metastatic colorectal cancer (mCRC) has the potential to improve prognosis and maintain quality of life than combination chemotherapy. The purpose of this study was to investigate the feasibility and effectiveness of a sequential treatment strategy consisting of an initial therapy (capecitabine, S-1, or 5-fluorouracil with leucovorin [LV/5-FU] plus bevacizumab) and subsequent therapy (i.e., initial therapy plus oxaliplatin) for mCRC. Methods: The primary endpoint was second progression-free survival (2nd PFS) between the start of initial therapy and tumor progression after sequential therapy; secondary endpoints were PFS after initial treatment, overall survival (OS), objective response rate (ORR), and safety. Results: Sixty-six patients were planned to be recruited. However, owing to a slow accrual rate, recruitment was terminated when only 19 patients were enrolled between 2011 and 2015; 4, 10, and 5 patients were administered capecitabine plus bevacizumab, S-1 plus bevacizumab, and LV/5-FU plus bevacizumab, respectively. The proportions of those with a KRAS status (wild-type/mutant/unknown) were 26%, 21%, and 53%, respectively. The median 2nd PFS and OS were 19.1 months and not reached, respectively. The ORR was 45.5% in the initial therapy and 16.7% in the subsequent therapy. Grade 3/4 toxicities included neutropenia (5%), proteinuria (5%), and hypertension (47%). Conclusion: Although our data are limited and preliminary, the sequential treatment strategy may provide a survival benefit in patients with mCRC. Further investigation of this treatment approach is warranted. [ABSTRACT FROM AUTHOR]

Neurotransmitters are endogenous chemical compounds that have the ability for neurotransmission and play a major role in shaping everyday life and functions. Cytotoxic drugs are a type of cancer and other diseases like rheumatoid arthritis, SLE, and different autoimmune syndromes treatment that utilize one or more chemotherapeutic agents as part of a regimen. The study aims are to calculate levels of neurotransmitters in patients receiving cytotoxic drugs and determined the effect of these agents on NTs concentration before and after. A prospective comparison study carried out before and after receives cytotoxic treatment for a period of three months from June 2020 to September 2020. Assessments of the studied samples will be conducted as a baseline before and after receiving drugs. A total of 50 participants were involved in the study. The blood samples were collected about 5 ml and diluted in the concentrated washing solution. The neurotransmitters evaluated are Adrenaline, Acetylcholine, Dopamine, Histamine, Glutamate, GABA, Serotonin, and Somatostatin. The mean age of the sample of the study was 49.28 ± 12.44. Patients with comorbidity conditions were 60%. The mean acetylcholine concentration pre and post receiving cytotoxic drugs was relatively not altering. Cytotoxic agents affected the mean epinephrine concentration, which was directly dropping to half. There was a decline of concentration of somatostatin post treatment compared with pre (from 33.83 ± 9.78 ng/L to 8.4 ± 2.66 ng/L), with a significant association (t-test=2.3, p=0.028). The mean concentration of dopamine pre was relatively unchanged from post-treatment. There was no differences association between pre and post mean level of histamine in this study. In this study, we found a high level of glutamine in the pre-phase (2025.4 ± 753.7 μmol/L), but it converted to normal level post treatment, with statistically significant differences (t-test=9.051, p<0.000). GABA concentration, the pre was above the normal range (1.31 ± 0.18 mumol/l), while the post was within normal, this dropping curve was statistically significant differences (t-test=9.442, p<0.000). There was a slight decrease in serotonin level among pre to post (from 366.6 ± 237.72 ng/mL to 298.77 ± 231.8 ng/mL), but these changes not significant. In conclusion, the NTs concentration may be altered by the administration of cytotoxic drugs in chronic diseases in a different pattern either decrease or return to normal. [ABSTRACT FROM AUTHOR]

Abstract Three‐dimensional biofabrication using photo‐crosslinkable hydrogel bioscaffolds has the potential to revolutionize the need for transplants and implants in joints, with articular cartilage being an early target tissue. However, to successfully translate these approaches to clinical practice, several barriers must be overcome. In particular, the photo‐crosslinking process may impact on cell viability and DNA integrity, and consequently on chondrogenic differentiation. In this review, we primarily explore the specific sources of cellular cytotoxicity and genotoxicity inherent to the photo‐crosslinking reaction, the methods to analyze cell death, cell metabolism, and DNA damage within the bioscaffolds, and the possible strategies to overcome these detrimental effects.

Cryptophycins are naturally occurring cytotoxins with great potential for chemotherapy. Since targeted therapy provides new perspectives for treatment of cancer, new potent analogues of cytotoxic agents containing functional groups for conjugation to homing devices are required. We describe the design, synthesis and biological evaluation of three new unit B cryptophycin analogues. The O-methyl group of the unit B D-tyrosine analogue was replaced by an O-(allyloxyethyl) moiety, an O-(hydroxyethyl) group, or an O-(((azidoethoxy)ethoxy)ethoyxethyl) substituent. While the former two maintain cytotoxicity in the subnanomolar range, the attachment of the triethylene glycol spacer with a terminal azide results in a complete loss of activity. Docking studies of the novel cryptophycin analogues to β-tubulin provided a rationale for the observed cytotoxicities.

Cytotoxic agents, also called antineoplastic agents, are used in cancer treatment due to their inherent activity to inhibit cell growth or proliferation, or DNA, RNA and protein synthesis. They are, therefore, hazardous by nature in a non-selective manner leading to disruption of cell growth and function of both diseased and healthy cells of treated patients. While the benefits of receiving cytotoxic agents may outweigh the incurred risks for patients, the same cannot be said for exposed healthcare practitioners involved in the transport, preparation, administration, and resulting waste disposal of these agents. Consequently, many professional bodies around the world have set standards of practice to prevent occupational exposure of healthcare workers to cytotoxic agents, and hospitals have been active in defining strict policies in this concern. However, due to the variability of the practice and infrastructure in academic settings, some activities performed within the cytotoxic academic research laboratory often do not adhere to recommendations published by guidelines. The present recommendations were therefore set forward by members of a working group who are experts on the subject matter representing academic, clinical, and research backgrounds in an attempt to promote safe cytotoxic handling in academic institutions. The document maps out the trajectory of cytotoxic agents being investigated in academic research laboratories while providing recommendations on the delivery, storage, use and disposal of cytotoxic agents in university settings. [ABSTRACT FROM AUTHOR]

Antibody drug conjugates (ADCs) normally compose of a humanized antibody and small molecular drug via a chemical linker. After decades of preclinical and clinical studies, a series of ADCs have been widely used for treating specific tumor types in the clinic such as brentuximab vedotin (Adcetris®) for relapsed Hodgkin's lymphoma and systemic anaplastic large cell lymphoma, gemtuzumab ozogamicin (Mylotarg®) for acute myeloid leukemia, ado-trastuzumab emtansine (Kadcyla®) for HER2-positive metastatic breast cancer, inotuzumab ozogamicin (Besponsa®) and most recently polatuzumab vedotin-piiq (Polivy®) for B cell malignancies. More than eighty ADCs have been investigated in different clinical stages from approximately six hundred clinical trials to date. This review summarizes the key elements of ADCs and highlights recent advances of ADCs, as well as important lessons learned from clinical data, and future directions. Antibody drug conjugates (ADCs), normally composed of a humanized antibody and small molecular drugs via chemical linkers, represent a rapidly growing field for cancer therapy. In this review, we provide an overview of ADCs in preclinical and clinical development, as well as future directions of ADCs. Image 1 [ABSTRACT FROM AUTHOR]

Sponges are multicellular animals which have cytotoxic compounds. In this study, isolation and cytotoxic activity of Penares sp sponge from Menjangan island-water West Bali National Park have been carried out. The results showed that chloroform extract and GF V Penares sp fraction were toxic according to Brine Shrimp Lethality Test method (each 85% and 63.3% mortality at 25μg/mL concentration). The isolation result of GF V fraction was obtained a compound (Spot 4) that is active as cytotoxic agent against T47D cells (IC50 of 12.7 ug/mL). Spot 4 is a terpenoid compound which has conjugated double bonds.

Rheumatic disease with visceral manifestations pose a potential problem for the disease course and its prognosis. Such visceral manifestations may include kidney damage or complications, particularly in certain cases bone, joint and muscular manifestations of rheumatic disease. Glomerular immune inflammatory diseases appear in cases where the rheumatic disease progresses to the point of becoming a systemic inflammatory process; AA-amyloidosis appears in cases of prolonged active articular process; while tubulo-interstitial lesion occurs during the treatment with non-steroidal anti-inflammatory drugs and analgesics. Progressive nature of kidney failure in rheumatic diseases, leading to the development of terminal renal insufficiency, presents a problem for the affected individuals in terms of their ability to live in conditions of renal replacement therapy.

Juniper representatives are natural sources of plenty of bioactive metabolites and have been used since ancient times as folk remedies against tapeworms, warts, cancer, etc. The antiproliferative activities of junipers are attributed to podophyllotoxin (PPT), which is a precursor for the synthesis of efficient anticancer drugs. However, the natural sources of PPT, Sinopodophyllum hexandrum (Royle) T. S. Ying and Podophyllum peltatum L., are already endangered species because of their intensive industrial exploitation. Therefore, identification of other sources of PPT is necessary. This study is a broad comparative investigation of junipers, for which original sources have been accessed from different continents of the world. The present research is aimed at the identification of species, producing PPT and other lignans at concentrations that are sufficient for the high antiproliferative activity of the corresponding extracts. Cytotoxic juniper leaf extracts demonstrated a broad spectrum of activity on a panel of cancer cell lines. The antiproliferative properties of junipers were attributed to the combined activity of great diversity of lignans (podophyllotoxin, deoxypodophyllotoxin, β-peltatin, yatein, matairesinol, anhydropodorhizol, etc.), detected by UHPLC-HRMS and LC-ESI-MS/MS in the corresponding extracts. Several species of the genus Juniperus L. were outlined as perspective sources of drug precursors with potential pharmaceutical applications.

Polytheonamide B (1) is a linear 48‐mer natural peptide with alternating d‐ and l‐amino acid residues. Compound 1 forms conducting channels for monovalent ions and exhibits potent cytotoxicity against MCF‐7 cells. Previously, we reported that nanomolar concentrations of 1 induce plasma membrane depolarization and lysosomal pH disruption, which triggers apoptosis. Here, we report the cellular localization and biological action of a simplified synthetic analogue of 1, polytheonamide mimic 3. Compared with 1, the toxicity of 3 against MCF‐7 cells is 16 times weaker. Although its plasma membrane depolarization effect is only 3.6 times lower, more 3 (20‐fold) is required to neutralize lysosomal pH. Thus, the effective concentrations for lysosomal neutralization and cytotoxicity by 3 are comparable. These results strongly suggest that the activity of 3 against the lysosomal membrane is more important for apoptotic cell death than its effects on the plasma membrane, and provide valuable information regarding the unique behavior of polytheonamide‐based molecules. [ABSTRACT FROM AUTHOR]

Schematic design showing the adipogenic differentiation assay. In this method, the cells are maintained for 14 days in contact with different test substance concentrations. This strategy allows the repeated dose approach. In this way, it is possible to visualize the influence of substances during the cell differentiation process. • Adipogenesis inhibition is a suitable and sensitive stem cell model for toxicity prediction. • The inhibition of adipogenesis can reduce animal use for ATC. • External and internal controls make this methodology feasible for regulatory use. In the present work, we established an adipogenesis inhibition assay as an adequate and sensitive in vitro model for reducing animal use by estimating the starting dose for the acute toxic class (ATC) method. First, human adipose-derived stem cells (ADSCs) underwent adipogenic differentiation induction for 14 days. Then, by high-content imaging analysis, we determined the percentage and area of cell differentiation that we considered suitable for negative and positive internal control according to the quality control criteria strictly standardized mean difference (SSMD) and robust SSMD. Moreover, we established sodium dodecyl sulfate (SDS) as an external positive control in this assay. To measure reduction in animal use to estimate the starting dose for the ATC method, we evaluated 10 chemicals representing Globally Harmonized System of Classification and Labeling of Chemicals (GHS) toxicity categories 1–5 and unclassified toxicity and determined the dose-response curves for percentage and area of cell differentiation by using the Hill function with an R2 ≥ 0.85. The resulting IC 50 values were used for LD 50 prediction and for estimating the starting dose for the ATC method. Our results indicated that use of the inhibition of adipogenesis assay to estimate the starting dose for the ATC method would decrease animal use for 7 out of 10 tested substances, possibly all substances if we consider the more toxic test substances in GHS categories 1, 2, and 3. We can conclude that the present assay is a suitable alternative to reduce animal testing in the first steps of predicting highly toxic substances. Moreover, this method also presents internal and external controls as differentials, which guarantee the quality of the assay as well as the results. These features are important for suggesting a methodology for regulatory purposes. [ABSTRACT FROM AUTHOR]

A new series of pyrido[2,3-d]pyrimidones incorporated pyrazoles and fused triazoles are synthesized and tested in vitro for cytotoxic effect against cancer cell lines: HePG-2, HCT-116, MCF-7, PC-3, and A-549. Their inhibition of protein kinase is assessed. The highest growth inhibitory (IC50 0.3 µM) effect is determined for one of compounds as compared with doxorubicin (IC50 0.6 µM). A modeling study is performed for approaching the compounds mode of binding and their similarity with the positive control drugs. [ABSTRACT FROM AUTHOR]

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In order to develop novel chemotherapeutic agents with potent anticancer activities, a series of new 2,5-diaryl/heteroaryl-1,3,4-oxadiazoles were designed and synthesized. The structures of the new compounds were established using elemental analyses, IR and NMR spectral data. The compounds were evaluated for their anticancer potential on two standardized human cell lines, HT-29 (colon adenocarcinoma) and MDA-MB-231 (breast adenocarcinoma). Cytotoxicity was measured by MTS assay, while cell cycle arrest and apoptosis assays were conducted using a flow cytometer, the results showing that the cell line MDA-MB-231 is more sensitive to the compounds’ action. The results of the predictive studies using the PASS application and the structural similarity analysis indicated STAT3 and miR-21 as the most probable pharmacological targets for the new compounds. The promising effect of compound 3e, 2-[2-(phenylsulfanylmethyl)phenyl]-5-(4-pyridyl)-1,3,4-oxadiazole, especially on the MDA-MB-231 cell line motivates future studies to improve the anticancer profile and to reduce the toxicological risks. It is worth noting that 3e produced a low toxic effect in the D. magna 24 h assay and the predictive studies on rat acute toxicity suggest a low degree of toxic risks.

The protein tubulin is central for maintaining normal cellular processes, and molecules interfering with the tubulin dynamics have potential in the treatment of cancerous diseases. The title compound, C17H14N2O5, was prepared as a lead compound in a project dedicated to the development of therapeutic agents binding to the colchicine binding site on tubulin, thereby interfering with the cell division in cancer cells. It holds many of the main structural characteristics for colchicine binding and has the potential for further modification and functionalization. In the title molecule, the benzene ring is inclined to the quinoline ring by 76.10 (8)°. In the crystal, molecules are linked by two pairs of C—H...O hydrogen bonds, forming tubular-like arrangements, propagating along the direction of the diagonals of the ab plane, and enclosing R22(26) and R22(16) ring motifs.