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Purpose: There is limited information about the clinical utility of targeted next-generation sequencing (NGS) panel testing to inform decision making for patients with advanced solid tumors. The Ontario-wide Cancer Targeted Nucleic Acid Evaluation (OCTANE) is a prospective study that enrolled more than 4,500 patients with solid tumor for NGS panel testing. We performed a retrospective survey of medical oncologists to evaluate the impact of NGS testing on treatment decisions., Methods: Patients and treating oncologists were identified at the Princess Margaret Cancer Center between 2016 and 2021. Tumor-only sequencing was performed using a gene panel of either 555 or 161 cancer genes. Oncologists were asked to review testing results and complete a survey indicating whether NGS testing affected treatment decisions. The primary outcome of this study was rate of treatment change on the basis of mutation results. Patient, test, and physician factors were evaluated for association with treatment changes using univariate analyses and a mixed-effects model., Results: Of the 582 surveys sent, 394 (67.7%) were completed. We found that 188 (47.7%) patients had testing results classified as actionable by the oncologist and 62 (15.7%) patients were matched to treatment, of whom 37 (60%) were enrolled in a clinical trial, 13 (21%) received an approved drug, four (6%) were prescribed off-label therapy, and eight (13%) avoided ineffective treatment. Patient, test, and physician characteristics were not significantly associated with treatment change. There was no difference in overall survival between patients who received matched treatment versus those who did not ( P = .55, median survival not reached)., Conclusion: OCTANE testing led to a change in drug treatment in 15.7% of patients, supporting the clinical utility of NGS panel testing for patients with advanced solid tumors.

The pyridoxal 5'-dependent enzyme methionine γ-lyase (MGL) catalyzes the degradation of methionine. This activity has been profitable to develop an antitumor agent exploiting the strict dependence of most malignant cells on the availability of methionine. Indeed, methionine depletion blocks tumor proliferation and leads to an increased susceptibility to anticancer drugs. Here, we explore the conjugation of MGL to gold nanoparticles capped with citrate (AuNPs) as a novel strategy to deliver MGL to cancer cells. Measurements of Transmission Electron Microscopy, Dynamic Light Scattering, Asymmetrical Flow Field-Flow Fractionation, X-ray Photoelectron Spectroscopy, and Circular Dichroism allowed to achieve an extensive biophysical and biochemical characterization of the MGL-AuNP complex including particle size, size distribution, MGL loading yield, enzymatic activity, and impact of gold surface on protein structure. Noticeably, we found that activity retention was improved over time for the enzyme adsorbed to AuNPs with respect to the enzyme free in solution. The acquired body of knowledge on the nanocomplex properties and this encouraging stabilizing effect upon conjugation are the necessary basis for further studies aimed at the evaluation of the therapeutic potential of MGL-AuNP complex in a biological milieu., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

The use of betalains, which are nitrogenous plant pigments, by the food industry is widespread and reflects their safety after intake. The recent research showed outstanding results for L-tryptophan-betaxanthin, a phytochemical present in traditional Chinese medicine, as an antitumoral agent when the activity was evaluated in the animal model Caenorhabditis elegans . Thus, L-tryptophan-betaxanthin is now presented as a lead compound, from which eleven novel structurally related betaxanthins have been designed, biotechnologically produced, purified, and characterized. The antitumoral effect of the derived compounds was evaluated on the JK1466 tumoral strain of C. elegans . All the tested molecules significantly reduced the tumoral gonad sizes in a range between 31.4% and 43.0%. Among the novel compounds synthesized, tryptophan methyl ester-betaxanthin and tryptophan benzyl ester-betaxanthin, which are the first betalains to contain an ester group in their structures, caused tumor size reductions of 43.0% and 42.6%, respectively, after administration to the model animal. Since these were the two most effective molecules, their mechanism of action was investigated by microarray analysis. Differential gene expression analysis showed that tryptophan methyl ester-betaxanthin and tryptophan benzyl ester-betaxanthin were able to down-regulate the key genes of the mTOR pathway, such as daf-15 and rict-1 .

Drug discovery has customarily focused on a de novo design approach, which is extremely expensive and takes several years to evolve before reaching the market. Discovering novel therapeutic benefits for the current drugs could contribute to new treatment alternatives for individuals with complex medical demands that are safe, inexpensive, and timely. In this consequence, when pharmaceutically yield and oncology drug efficacy appear to have hit a stalemate, drug repurposing is a fascinating method for improving cancer treatment. This review gathered about how in silico drug repurposing offers the opportunity to quickly increase the anticancer drug arsenal and, more importantly, overcome some of the limits of existing cancer therapies against both old and new therapeutic targets in oncology. The ancient nononcology compounds' innovative potential targets and important signaling pathways in cancer therapy are also discussed. This review also includes many plant-derived chemical compounds that have shown potential anticancer properties in recent years. Here, we have also tried to bring the spotlight on the new mechanisms to support clinical research, which may become increasingly essential in the future; at the same time, the unsolved or failed clinical trial study should be reinvestigated further based on the techniques and information provided. These encouraging findings, combined together, will through new insight on repurposing more non-oncology drugs for the treatment of cancer., Competing Interests: None

Objective: Pediatric cancer patients have an increased risk of stroke. However, there is a knowledge gap regarding stroke in early stages of pediatric cancer. The objective of this project is to describe the current knowledge on stroke in pediatric cancer patients., Design: Systematic review., Materials and Methods: After Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines, literature search was conducted in PubMed, Cochrane, and Google Scholar from January 1, 1995, up to February 1, 2022., Results: A total of 3499 studies were identified, of which 8 met inclusion criteria. The incidence of stroke in pediatric cancer patients varied between 0.47% and 2.9%, and prevalence between 1% and 3%. The risk factors identified were leukemia diagnosis, cranial radiation, thrombocytopenia, coagulopathy, and infection. There was a higher rate of diagnosis with magnetic resonance imaging than with computed tomography scan. Treatment was inconsistent, and patients with cancer were less likely to receive antithrombotic treatment when compared with patients without cancer. The highest mortality was among hemorrhagic stroke. Recurrence rate was 5% to 19%., Conclusions: The risk for stroke is increased in the pediatric cancer population and can lead to devastating results. The available reports include few patients, with heterogeneous cancer diagnoses and outcomes. Large-scale multicenter studies are needed, focusing on early diagnosis, risk factors, and management strategies of stroke in children with underlying cancer., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The communication between tumor cells and the microenvironment plays a fundamental role in the development, growth and further immune escape of the tumor. This communication is partially regulated by extracellular vesicles which can direct the behavior of surrounding cells. In recent years, it has been proposed that this feature could be applied as a potential treatment against cancer, since several studies have shown that tumors treated with radiotherapy can elicit a strong enough immune response to eliminate distant metastasis; this phenomenon is called the abscopal effect. The mechanism behind this effect may include the release of extracellular vesicles loaded with damage-associated molecular patterns and tumor-derived antigens which activates an antigen-specific immune response. This review will focus on the recent discoveries in cancer cell communications via extracellular vesicles and their implication in tumor development, as well as their potential use as an immunotherapeutic treatment against cancer.

Objectives.: Motivation for the study. The impact of the COVID-19 pandemic on the risk of death in cancer patients on chemotherapy and immunotherapy is controversial. Published studies mainly compared patients on anti-cancer therapy to those off treatment or COVID-19 positive cancer patients to COVID-19 negative ones. Few studies were conducted in developing countries. Main findings. Mortality didn't increase in unvaccinated outpatients on active intravenous oncology treatment during the COVID-19 pandemic. Implications. This is the first propensity score-matched cohort study evaluating the impact of the COVID-19 pandemic on the population of unvaccinated oncology patients receiving intravenous anticancer therapy. . To compare all-cause mortality of unvaccinated oncology patients who received chemotherapy or immunotherapy during the pandemic with those treated before the pandemic., Materials and Methods.: We conducted a cohort study in four tertiary hospitals in Argentina. Outpatients with a solid neoplasm of any stage under-going cytotoxic or intravenous immunotherapy were eligible. The pandemic cohort was enrolled during the initial phase of the outbreak and compared with a pre-pandemic cohort using propensity score matching (PSM). Subjects were matched for age, sex, health insurance, risk factors for severe COVID-19 complications, performance status, cancer type and treatment, line of treatment, and body mass index. All-cause mortality was estimated for both cohorts after 6 months of follow-up., Results.: A total of 169 patients were recruited between April and August 2020 for the pandemic cohort and 377 for the pre-pandemic cohort in the same months of 2019; 168 patients were matched. After PSM, all-cause mortality was 17.9% in the pandemic cohort and 18.5% in the pre-pandemic cohort; the Relative Risk was 0.97 (95 % confidence interval: 0.61-1.52; p=0.888). In the pandemic cohort, 30/168 patients died, but none from COVID-19., Conclusions.: Our findings show that the mortality rate of unvaccinated ambulatory patients on active intravenous oncology treatment during the COVID-19 pandemic did not increase.

Background: There is a paucity of multicenter data describing the impact of coronavirus disease 2019 (COVID-19) on hospitalized pediatric oncology patients. Using a large, multicenter, Society of Critical Care Medicine (SCCM) Discovery Viral Infection and Respiratory Illness University Study (VIRUS) database, we aimed at assessing outcomes of COVID-19 infection in this population., Method: This is a matched-cohort study involving children below 18 years of age hospitalized with COVID-19 between March 2020 and January 2021. Using the VIRUS; COVID-19 Registry database, children with oncologic diseases were compared with propensity score matched (age groups, sex, race, and ethnicity) cohort of children without oncologic diseases for the prevalence of Multisystem Inflammatory Syndrome in Children (MIS-C), intensive care unit (ICU) admission, interventions, hospital, and ICU length of stay., Results: The number of children in the case and control groups was 45 and 180, respectively. ICU admission rate was similar in both groups ([47.7 vs 51.7%], P =0.63). The proportion of children requiring noninvasive and invasive mechanical ventilation, and its duration were similar between groups, same as hospital mortality. Interestingly, MIS-C was significantly lower in the oncology group compared with the control (2.4 vs 24.6%; P =0.0002)., Conclusions: In this study using a multicenter VIRUS database, ICU admission rate, interventions, and outcomes of COVID-19 were similar in children with the oncologic disease compared with control patients. The incidence of MIS-C is lower in oncologic patients., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Development of fluorescent imaging probes is an important topic of research for the early diagnosis of cancer. Based on the difference between the cellular environment of tumor cells and normal cells, several "smart" fluorescent probes have been developed. In this work, a glycopolymer functionalized Förster resonance energy transfer (FRET) based fluorescent sensor is developed, which can monitor the pH change in cellular system. One-pot sequential reversible addition-fragmentation chain transfer (RAFT)polymerization technique is employed to synthesize fluorescent active triblock glycopolymer that can undergo FRET change on the variation of pH. A FRET pair, fluorescein o-acrylate (FA) and 7-amino-4-methylcoumarin (AMC) is linked via a pH-responsive polymer poly [2-(diisopropylamino)ethyl methacrylate] (PDPAEMA), which can undergo reversible swelling/deswelling under acidic/neutral condition. The presence of glycopolymer segment provides stability, water solubility, and specificity toward cancer cells. The cellular FRET experiments on cancer cells (MDA MB 231) and normal cells (3T3 fibroblast cells) demonstrate that the material is capable of distinguishing cells as a function of pH change., (© 2022 Wiley-VCH GmbH.)

Nowadays, discovering an effective and safe anticancer medication is one of the major challenges. Premature death due to the unidirectional toxicity of conventional therapy is common in cancer patients with poor health status. Plants have been used as medicine since prehistoric times, and extensive research on the anticancer properties of various bioactive phytomolecules is ongoing. Pentacyclic triterpenoids are secondary metabolites of plants with well-known cytotoxic and chemopreventive properties established in numerous cancer research studies. The lupane, oleanane, and ursane groups of these triterpenoids have been well-studied in recent decades for their potential antitumor activity. This review delves into the molecular machinery governing plant-derived triterpenes' anticancer efficacy. The highlighted mechanisms are antiproliferative activity, induction of apoptosis through regulation of BCL-2 and BH3 family proteins, modulation of the inflammatory pathway, interference with cell invagination and inhibition of metastasis. Lack of solubility in mostly used biological solvents is the major barrier to the therapeutic progress of these triterpenoids. This review also highlights some probable ways to mitigate this issue with the help of nanotechnology and the modification of their physical forms., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Oncosis (from Greek ónkos, meaning "swelling") is a non-apoptotic cell death process related to energy depletion. In contrast to apoptosis, which is the main form of cell death induced by anticancer drugs, oncosis has been relatively less explored but holds potential to overcome drug resistance phenomena. In this study, we report a novel rationally designed mitochondria-targeted iridium(III) complex (OncoIr3) with advantageous properties as a bioimaging agent. OncoIr3 exhibited potent anticancer activity in vitro against cancer cells and displayed low toxicity to normal dividing cells. Flow cytometry and fluorescence-based assays confirmed an apoptosis-independent mechanism involving energy depletion, mitochondrial dysfunction and cellular swelling that matched with the oncotic process. Furthermore, a Caenorhabditis elegans tumoral model was developed to test this compound in vivo, which allowed us to prove a strong oncosis-derived antitumor activity in animals (with a 41% reduction of tumor area). Indeed, OncoIr3 was non-toxic to the nematodes and extended their mean lifespan by 18%. Altogether, these findings might shed new light on the development of anticancer metallodrugs with non-conventional modes of action such as oncosis, which could be of particular interest for the treatment of apoptosis-resistant cancers., (© 2022. The Author(s).)

Background: Cancer is a serious problem throughout the world. The pathophysiology of cancer is multifactorial and is also related to gut microbiota. Intestinal microbes are the useful resident of the healthy human. They are significant for various aspects of human health, including nutritional biotransformation, flushing of the pathogens, toxin neutralization, immune response, and onco-suppression. Disruption in the interactions among the gut microbiota, intestinal epithelium, and the host immune system are associated with gastrointestinal disorders, neurodegenerative diseases, metabolic syndrome, and cancer. Probiotic bacteria (Lactobacillus spp., Bifidobacterium spp.) have been regarded as beneficial to health. Moreover, they also play a significant role in immunomodulation and a preventive measure against obesity, diabetes, liver disease, inflammatory bowel disease, tumor progression, and cancer., Objective: The involvement of gut microorganisms in cancer development and prevention has been recognized as a balancing factor. The events of dysbiosis emphasize metabolic disorder and carcinogenesis. The gut flora potentiates immunomodulation and minimizes the limitations of usual chemotherapy. The significant role of prebiotics and probiotics on the improvement of immunomodulation and antitumor properties has been considered., Methods: I had reviewed the literature on the multidimensional activities of prebiotics and probiotics from the NCBI website database PubMed, Springer Nature, Science Direct (Elsevier), Google Scholar database to search relevant articles. Specifically, I had focused on the role of prebiotics and probiotics in immunomodulation and cancer prevention., Results: Prebiotics are the nondigestible fermentable sugars that selectively influence the growth of probiotic organisms that exert immunomodulation over the cancerous growth. The oncostatic properties of bacteria are mediated through the recruitment of cytotoxic T cells, natural killer cells, and oxidative stress-induced apoptosis in the tumor microenvironment. Moreover, approaches have also been taken to use probiotics as an adjuvant in cancer therapy., Conclusion: The present review has indicated that dysbiosis is a crucial factor in many pathological situations, including cancer. Applications of prebiotics and probiotics exhibit the immune-surveillance as oncostatic effects. These events increase the possibilities of new therapeutic strategies for cancer prevention., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Melatonin is primarily synthesized in the pineal gland under the influence of noradrenergic stimulation at night. It regulates the sleep-wake cycle, gonadal activity, redox homeostasis, immune functions, and anticarcinogenic effects at the normal physiological state. The activity of melatonin is mediated by membrane-bound G protein-coupled receptors MT1 and MT2. Circadian deregulation, exposure to light-at-night, shift work, and jet lag disrupt the melatonin rhythm. A low level of circulatory melatonin concentration influences the development of many cancers, including breast cancer. Melatonin acts as an anticancer agent in breast tissue. It suppresses metabolic activity, regulates cell-signaling pathways, and subsequently blocks cell proliferation. This indolamine induces apoptosis, inhibits chronic inflammation and metastasis. Melatonin restricts the functions of estrogen receptor α and also inhibits aromatase activity. Melatonin is a potent antioxidant that reduces the chemoresistance capacity of breast cancer cells. At therapeutic levels, it potentially increases the efficacy of chemotherapeutic agents and decreases their adverse effects during the treatment of breast cancer. The present review focuses on the antineoplastic activity of melatonin against breast cancer. Emphasis has been given to the possible use of melatonin in the treatment of breast cancer.

Cancer begins due to uncontrolled cell division. Cancer cells are insensitive to the signals that control normal cell proliferation. This uncontrolled cell division is due to the accumulation of abnormalities in different factors associated with the cell division, including different cyclins, cell cycle checkpoint inhibitors, and cellular signaling. Cellular signaling pathways are aberrantly activated in cancer mainly due to epigenetic regulation and post-translational regulation. In this chapter, the role of epigenetic regulation in aberrant activation of PI3K/AKT, Ras, Wnt, Hedgehog, Notch, JAK/STAT, and mTOR signaling pathways in cancer progression is discussed. The role of epigenetic regulators in controlling the upstream regulatory proteins and downstream effector proteins responsible for abnormal cellular signaling-mediated cancer progression is covered in this chapter. Similarly, the role of signaling pathways in controlling epigenetic gene regulation-mediated cancer progression is also discussed. We have tried to ascertain the current status of potential epigenetic drugs targeting several epigenetic regulators to prevent different cancers., (© 2022. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

We have developed an amphiphilic pH probe (P1CS) to detect pH levels in the plasma membrane in cancer cells. An elevated fluorescence signal at 550 nm at the cell surface of cancer cells (MDA-MB-231, HeLa cells) prompted the application of P1CS as a pH marker for the cancer cell surface, discriminating it from normal cells (WI-38). Moreover, the probe enables labeling of the surface of multilayered tumor spheroids, which promotes its use as a marker for the surface of tumor tissue.

Circadian (~ 24-hour) rhythm has been observed in all living organisms. In humans, the circadian system governs different physiological functions such as metabolism, sleep-wake cycle, body temperature, hormone secretion, and cellular proliferation. The suprachiasmatic nucleus (SCN) of the anterior hypothalamus is the principal circadian pacemaker. The SCN receives input signals primarily from the retinohypothalamic tract (RHT), sends output signals to different parts of the hypothalamus, pineal gland, and the peripheral clocks through the neural or humoral network. The functions of the circadian clock are mediated by the rhythmic expression of the core clock genes through a complex feedback loop. Disruption of clock functions influences the development of several pathologic conditions, including cancer, shift work, chronic or acute jet lag, and light-at-night affect the circadian activity, leading to development of several physiological disorders, more specifically cancer. Circadian dysfunction alters the expression of core clock genes that promote the deregulation of the cell cycle, increase cell proliferation and survival, decrease apoptotic activity, alter metabolic functions, increase metastatic property, collectively induces cancer progression.

Urine cell-free DNA is an important source of diagnostic markers for different diseases, especially for cancer. It could be important to achieve the urine cell-free DNA integrity to establish its provenience from cancer cells or dead inflammatory cells for necrosis in urine or from normal cells with the purpose to use it as an early diagnostic tool for urological cancers or other diseases. Here we describe a simple, noninvasive approach from urine collection to DNA integrity analysis using real-time PCR.

Opinion Statement: The importance of assessing health-related quality of life (HRQoL) and patient-reported outcomes (PROs) is now well recognized as an essential measure when evaluating the effectiveness of new cancer therapies. Quality of life measures provide for a multi-dimensional understanding of the impact of cancer treatment on measures ranging from functional, psychological, and social aspects of a patient's health. Patient-reported outcomes provide for an assessment of physical and functional symptoms that are directly elicited from patients. Collection of PROs and HRQoL data has been shown to not only be feasible but also provide for reliable measures that correlate with established outcomes measures better than clinician-scored toxicities. The importance of HRQoL measures has been emphasized by both patients and clinicians, as well as policy makers and regulatory bodies. Given the benefits associated with measuring HRQoL and PROs in oncology clinical trials, it is increasingly important to establish methods to effectively incorporate PROs and HRQoL measures into routine clinical practice.

Purpose: Melatonin is an amphipathic indolamine molecule ubiquitously present in all organisms ranging from cyanobacteria to humans. The pineal gland is the site of melatonin synthesis and secretion under the influence of the retinohypothalamic tract. Some extrapineal tissues (skin, lens, gastrointestinal tract, testis, ovary, lymphocytes, and astrocytes) also enable to produce melatonin. Physiologically, melatonin regulates various functions like circadian rhythm, sleep-wake cycle, gonadal activity, redox homeostasis, neuroprotection, immune-modulation, and anticancer effects in the body. Inappropriate melatonin secretion advances the aging process, tumorigenesis, visceral adiposity, etc. METHODS: For the preparation of this review, I had reviewed the literature on the multidimensional activities of melatonin from the NCBI website database PubMed, Springer Nature, Science Direct (Elsevier), Wiley Online ResearchGate, and Google Scholar databases to search relevant articles. Specifically, I focused on the roles and mechanisms of action of melatonin in cancer prevention., Results: The actions of melatonin are primarily mediated by G-protein coupled MT1 and MT2 receptors; however, several intracellular protein and nuclear receptors can modulate the activity. Normal levels of the melatonin protect the cells from adverse effects including carcinogenesis. Therapeutically, melatonin has chronomedicinal value; it also shows a remarkable anticancer property. The oncostatic action of melatonin is multidimensional, associated with the advancement of apoptosis, the arrest of the cell cycle, inhibition of metastasis, and antioxidant activity., Conclusion: The present review has emphasized the mechanism of the anti-neoplastic activity of melatonin that increases the possibilities of the new approaches in cancer therapy.

Pressure ulcers lead to discomfort for patients and may have an important impact on a patient's quality of life. Measure the incidence and prevalence of pressure ulcers in a Hospice environment; evaluate the risk factors associated with pressure ulcers; and calculate the incidence of Kennedy Terminal Pressure Ulcers. This multicentre prospective cohort study enrolled 440 cancer patients in advanced phase, consecutively admitted to five hospices of the AUSL della Romagna (Italy), during a period of 1 year. Five hundred more patients were excluded from the study because of inability to sign the consent form or refusal to participate. All patients were adults above 18 years of age. The National Pressure Advisory Panel Classification System was used to evaluate the pressure ulcers. Potential risk predictors were evaluated through the Braden Scale, the Numerical Scale, and the Pain Assessment in Advanced Dementia Scale. Starting in September 2016, 214 (48.6%) females and 226 (51.4%) males were analysed. The incidence of pressure ulcers in the total population was 17.3%. The risk factors that influence the development of pressure ulcers were age, proximity to death, and duration of stay in Hospice. The incidence of Kennedy Terminal Pressure Ulcers was 2.7%. This study demonstrates that 17.3% of all patients admitted to a hospice setting developed a pressure ulcer. The longer the patients stay in hospice and the clinical condition deteriorates, the higher the risk of developing a pressure ulcer., (© 2020 Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Urine could be a convenient source of biomarkers for different diseases and clinical applications, mostly for cancer diagnosis, prognosis, treatment monitoring, and prenatal diagnosis. The ultra-noninvasive sampling and the possibility to analyze large volume are the main undisputed advantages of urine-based protocols. Recent and comprehensive studies showed that urinary cell-free DNA (ucfDNA) is informative to identify the genomic signature of patients, resulting in a huge tool to track the tumor evolution and for personalized medicine in urological and non-urological cancer.In this chapter, we reported the main published evidences on ucfDNA, with the aim at discussing its promising and translatable role in clinical practices.

The exploitation of methionine-depleting enzyme methionine γ-lyase (MGL) is a promising strategy against specific cancer cells that are strongly dependent on methionine. To identify MGL from different sources with high catalytic activity and efficient anticancer action, we have expressed and characterized MGL from Clostridium novyi and compared its catalytic efficiency with the previously studied MGL from Citrobacter freundii. The purified recombinant MGL exhibits k cat and k cat /K m for methionine γ-elimination reaction that are 2.4- and 1.36-fold higher than C. freundii enzyme, respectively, whereas absorption, fluorescence, and circular dichroism spectra are very similar, as expected on the basis of 87% sequence identity and high conservation of active site residues. The reactivity of cysteine residues with DTNB and iodoacetamide was investigated as well as the impact of their chemical modification on catalytic activity. This information is relevant because for increasing bioavailability and reducing immunogenity, MGL should be decorated with polyethylene glycol (PEG). It was found that Cys118 is a faster reacting residue, which results in a significant decrease in the γ-elimination activity. Thus, the protection of Cys118 before conjugation with cysteine-reacting PEG represents a valuable strategy to preserve MGL activity. The anticancer action of C. novyi MGL, evaluated in vitro against prostate (PC-3), chronic myelogenous leucemia (K562), and breast (MDA-MB-231 and MCF7) cancer cells, exhibits IC 50 of 1.3 U mL -1 , 4.4 U mL -1 , 1.2 U mL -1 , and 3.4 U mL -1 , respectively. A higher cytotoxicity of C. novyi MGL was found against cancer cells with respect to C. freundii MGL, with the exception of PC-3, where a lower cytotoxicity was observed. © 2017 IUBMB Life, 69(9):668-676, 2017., (© 2017 International Union of Biochemistry and Molecular Biology.)

Background: The BRAF protein kinase is widely studied as a cancer driver and therapeutic target. However, the regulation of its expression is not completely understood., Results: Taking advantage of the RNA-seq data of more than 4800 patients belonging to 9 different cancer types, we show that BRAF mRNA exists as a pool of 3 isoforms (reference BRAF, BRAF-X1, and BRAF-X2) that differ in the last part of their coding sequences, as well as in the length (BRAF-ref: 76 nt; BRAF-X1 and BRAF-X2: up to 7 kb) and in the sequence of their 3'UTRs. The expression levels of BRAF-ref and BRAF-X1/X2 are inversely correlated, while the most prevalent among the three isoforms varies from cancer type to cancer type. In melanoma cells, the X1 isoform is expressed at the highest level in both therapy-naïve cells and cells with acquired resistance to vemurafenib driven by BRAF gene amplification or expression of the Δ[3-10] splicing variant. In addition to the BRAF-ref protein, the BRAF-X1 protein (the full length as well as the Δ[3-10] variant) is also translated. The expression levels of the BRAF-ref and BRAF-X1 proteins are similar, and together they account for BRAF functional activities. In contrast, the endogenous BRAF-X2 protein is hard to detect because the C-terminal domain is selectively recognized by the ubiquitin-proteasome pathway and targeted for degradation., Conclusions: By shedding light on the repertoire of BRAF mRNA and protein variants, and on the complex regulation of their expression, our work paves the way to a deeper understanding of a crucially important player in human cancer and to a more informed development of new therapeutic strategies.

Introduction: Although the role of circulating cell free DNA in cancer has been widely demonstrated, less is known about the role of urine cell free DNA (UcfDNA). UcfDNA can serve as a 'liquid biopsy' for urological and non-urological tumors, as it carries information on DNA from cells exfoliated in urine and from circulation. Areas covered: We review the studies on UcfDNA as a source of biomarkers for cancer, focusing on the new techniques and the differences between urological and non-urological tumors. We searched Pubmed for articles published between 1998 and 2016 with the following key words and phrases: 'urine' and 'cell free DNA' or 'liquid biopsy' or 'cancer'. Expert commentary: Despite the few papers published on this topic, UcfDNA is an important component of 'liquid biopsy', a useful and non-invasive tool for cancer diagnosis, prognosis and treatment monitoring, containing a wide range of genetic information.

Clinical trials using antiangiogenic drugs revealed their potential against cancer. Unfortunately, a large percentage of patients does not yet benefit from this therapeutic approach highlighting the need of diagnostic tools to non-invasively evaluate and monitor response to therapy. It would also allow to predict which kind of patient will likely benefit of antiangiogenic therapy. Reasons for treatment failure might be due to a low expression of the drug targets or prevalence of other pathways. Molecular imaging has been therefore explored as a diagnostic technique of choice. Since the vascular endothelial growth factor (VEGF/VEGFR) pathway is the main responsible of tumor angiogenesis, several new drugs targeting either the soluble ligand or its receptor to inhibit signaling leading to tumor regression could be involved. Up today, it is difficult to determine VEGF or VEGFR local levels and their non-invasive measurement in tumors might give insight into the available target for VEGF/VEGFR-dependent antiangiogenic therapies, allowing therapy decision making and monitoring of response.

In vivo selection of phage display libraries have been exploited successfully in the past to isolate various high affinity conformationally strained cyclic peptide ligands (CX(5-7)C, peptides flanked by a cysteine residue on each side) for integrin receptors capable of selectively homing to tumor vasculatures. Previously, such phase display library studies have shown that integrin alpha 5 beta 1 binds with high affinity to cyclic peptides containing CRGDGWC motif. Herein we show that a lipopeptide with just the RGDGW motif (without the flanking cysteine groups) covalently attached to the lysine residue of a monolysinylated cationic amphiphile (RGDGWK-lipopeptide 1) delivers genes to cultured cells preferably via alpha 5 beta 1 integrins. Importantly, remarkable tumor growth inhibition was observed when the electrostatic complex of the RGDGWK-lipopeptide 1 and the anti-cancer p53 gene was intravenously administered in C57BL/6J mice bearing the aggressive B16F10 tumor. Immunohistochemical staining of mice tumor cryosections with vasculature markers combined with monitoring expression of the green fluorescence protein in the same tumor cryosections revealed that the RGDGWK-lipopeptide 1 targets genes to tumor vasculatures. The colocalization of the TUNEL (terminal deoxyuridine triphosphate nick-end labeling, a widely used marker of apoptosis) and VE-cadherin (markers of tumor endothelial cells) positive cells in tumor cryosections support the notion that the remarkable tumor growth inhibition property of the RGDGWK-lipopeptide 1:p53 complex is initiated through apoptosis of the tumor endothelial cells., ((c) 2009 Elsevier Ltd. All rights reserved.)