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Background: Hypersensitivity reactions to anticancer chemotherapy and monoclonal antibodies may lead to discontinuation of first-line treatment options. Identification of these reactions can provide specific diagnosis and treatment by rapid drug desensitizations., Objective: To determine the hypersensitivity reactions involved in anticancer chemotherapy and monoclonal antibodies, and the safety and efficacy of rapid drug desensitization., Methods: We conducted an observational study of hypersensitivity reaction presented after the administration of anticancer chemotherapy and monoclonal antibodies in Mexico. We documented the symptoms of initial reaction and their severity, and the results of skin tests. We also report our experience of the administration of 12-step (mild-moderate reactions) and 16-step (severe reactions) desensitization protocols in these patients., Results: Overall, 93 patients received 336 rapid drug desensitization; 105 to taxanes, 115 to platinum drugs, 101 to monoclonal antibodies, and 15 other anticancer chemotherapy. Hypersensitivity reaction to taxanes occurred in the first or second administration, platinum drugs after the sixth cycle, and rituximab in the first cycle. The most common symptom in carboplatin was urticaria, paclitaxel back pain, oxaliplatin and docetaxel dyspnea, and in the monoclonal antibodies cardiovascular symptoms. Skin tests were positive in 75% of the carboplatin group, and only 16.7% in docetaxel. There was a rapid drug desensitization success rate of 99.4% and 85.7% did not present any related hypersensitivity reaction., Conclusion: The diagnosis of hypersensitivity reaction to anticancer chemotherapy and monoclonal antibodies offers a panorama in the management of oncological diseases. Our standardized desensitization protocol is safe and effective and can be reproduced in other centers to treat patients who need to maintain first-line treatment., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. The manuscript has not been published elsewhere and is not under consideration for publication elsewhere.

Introduction: We report a case of advanced testicular cancer cured by early and appropriate resumption of chemotherapy even after COVID-19 infection during induction chemotherapy., Case Presentation: The patient was a healthy 36-year-old male. The diagnosis was a stage IIIB nonseminoma (pT2N2M1a). On day 14 of the first chemotherapy cycle, the patient was diagnosed with mild COVID-19. The second chemotherapy cycle was initiated with a 1-day delay (on day 10 after the COVID-19 diagnosis). The patient achieved remission with minimal postponement of chemotherapy., Conclusion: Only a few case reports have described the resumption of anticancer chemotherapy in patients with COVID-19. In deciding when to resume chemotherapy after COVID-19 infection, it is essential to consider factors such as cancer type, progression, and severity of COVID-19 and should be tailored to individual patient needs., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors. IJU Case Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Urological Association.)

The elevated glutathione (GSH) level in cancer cells contributes to the poor response to chemotherapy and necessitates the use of maximum tolerated drug doses, leading to myriad side effects. We have developed a biocompatible and fluorescently trackable nanosystem, iron(III)-bound nanocarbonaceous polyphenol (FeNCP), to modulate the available GSH pool in cancer cells for synergistic effects in treatments with a cytotoxic anticancer drug, doxorubicin (Dox). This nanosystem was designed using a nanoscale carbon system as a platform to generate a GSH-responsive gallic acid-iron complex. The effective interaction between FeNCP and GSH was probed in PBS (pH 7.4) and cell lysates using UV-Vis, fluorescence spectrophotometry, 1 H NMR, flow cytometry, and confocal and transmission electron microscopic studies. The concurrent treatment of cancer cells with subcytotoxic FeNCP and Dox leads to dose reduction indices of Dox of ∼6.1 for HepG2 (hepatocellular carcinoma) and 6.7 for B16F0 (melanoma) to kill ∼50% of the cell population, which is suggestive of the requirement of a multifold lower dose of Dox. Notably, this combination was relatively more cytotoxic toward cancer cell lines than the model normal cell line, Vero. The increased reactive oxygen species levels in combinatorial treatment reveal that FeNCP serves as a potential candidate for modulating glutathione activity and potentiating cytotoxic effects of Dox. The intelligent multifold design of this nanosystem might enable the applicability in optical detection of GSH and imaging-assisted surgery in the future, in addition to the potential to advance treatment regimens in anticancer chemotherapy.

Metal-based complexes have occupied a pioneering niche in the treatment of many chronic diseases, including various types of cancers. Despite the phenomenal success of cisplatin for the treatment of many solid malignancies, a limited number of metallo-drugs are in clinical use against cancer chemotherapy till date. While many other prominent platinum and non‑platinum- based metallo-drugs (e.g. NAMI-A, KP1019, carboplatin, oxaliplatin, titanocene dichloride, casiopeinas® etc) have entered clinical trials, many have failed at later stages of R&D due to deleterious toxic effects, intrinsic resistance and poor pharmacokinetic response and low therapeutic efficacy. Nonetheless, research in the area of medicinal inorganic chemistry has been increasing exponentially over the years, employing novel target based drug design strategies aimed at improving pharmacological outcomes and at the same time mitigating the side-effects of these drug entities. Over the last few decades, natural products became one of the key structural motifs in the anticancer drug development. Many eminent researchers in the area of medicinal chemistry are devoted to develop new 3d-transition metal-based anticancer drugs/repurpose the existing bioactive compounds derived from myriad pharmacophores such as coumarins, flavonoids, chromones, alkaloids etc. Metal complexes of natural alkaloids and their analogs such as luotonin A, jatrorrhizine, berberine, oxoaporphine, 8-oxychinoline etc. have gained prominence in the anticancer drug development process as the naturally occurring alkaloids can be anti-proliferative, induce apoptosis and exhibit inhibition of angiogenesis with better healing effect. While some of them are inhibitors of ERK signal-regulated kinases, others show activity based on cyclooxygenases-2 (COX-2) and telomerase inhibition. However, the targets of these alkaloid complexes are still unclear, though it is well-established that they demonstrate anticancer potency by interfering with multiple pathways of tumorigenesis and tumor progression both in vitro and in vivo. Over the last decade, many significant advances have been made towards the development of natural alkaloid-based metallo-drug therapeutics for intervention in cancer chemotherapy that have been summarized below and reviewed in this article., 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 © 2022 Elsevier Inc. All rights reserved.)

Reactive oxygen species (ROS) play essential roles in the body, such as the production of energy in oxidative phosphorylation and signal transduction for homeostasis. Redox balance in biological systems gradually collapses due to various environmental factors, including aging and disease, and induces oxidative stress in the body. None of the natural or synthetic antioxidants have been approved clinically, owing to their adverse effects. Herein, we developed L -cysteine (Cys)-based polymer micelles as new self-assembling antioxidants to reduce the adverse effects of conventional antioxidants. Poly(ethylene glycol)-block-poly(L-cysteine) (PEG-block-PCys) was synthesized via anionic ring-opening polymerization. Because the free SH groups in the side chains of the PCys segment were protected by disulfide bonds, the obtained block copolymers were amphiphilic and formed polymer micelles (Nano Cys s) of tens of nanometers in size in aqueous media. The stability of Nano Cys s in the presence of bovine serum albumin (BSA) was increased by increasing the molecular weight (MW) of the PCys segments, which was analyzed using dynamic light scattering (DLS). The size and coagulation tendency of Nano Cys s were also analyzed using DLS measurements by changing the pH and NaCl concentration. Nano Cys s were confirmed to be less toxic both in vitro and in vivo than N-acetylcysteine (NAC) because of their size and biocompatible PEG surface layer. Intraperitoneal (i.p.) administration of Nano Cys s to the tumor xenograft mouse model successfully suppressed tumor growth. Interestingly, this effect depended on the MW of the PCys segments., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yukio Nagasaki reports financial support was provided by the Japanese Society for the Promotion of Science., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Copper is an endogenous metal ion that has been studied to prepare a new antitumoral agent with less side-effects. Copper is involved as a cofactor in several enzymes, in ROS production, in the promotion of tumor progression, metastasis, and angiogenesis, and has been found at high levels in serum and tissues of several types of human cancers. Under these circumstances, two strategies are commonly followed in the development of novel anticancer Copper-based drugs: the sequestration of free Copper ions and the synthesis of Copper complexes that trigger cell death. The latter strategy has been followed in the last 40 years and many reviews have covered the anticancer properties of a broad spectrum of Copper complexes, showing that the activity of these compounds is often multi factored. In this work, we would like to focus on the anticancer properties of mixed Cu(II) complexes bearing substituted or unsubstituted 1,10-phenanthroline based ligands and different classes of inorganic and organic auxiliary ligands. For each metal complex, information regarding the tested cell lines and the mechanistic studies will be reported and discussed. The exerted action mechanisms were presented according to the auxiliary ligand/s, the metallic centers, and the increasing complexity of the compound structures.

Boronic acid (and ester) prodrugs targeting the overexpressed level of reactive oxygen species within tumor microenvironment represent a promising area for the discovery of new selective anticancer chemotherapy. This strategy that emerged only ten years ago is exponentially growing and could demonstrate its clinical usefulness in the near future. Herein, the previously described small-molecule and macromolecular anticancer prodrugs activated by carbon-boron oxidation are gathered. This review reports on the most interesting derivatives mentioned in the literature based on the in vitro and in vivo activity when available. Eventually, the pharmacological applicability of this strategy is discussed, in particular, the kinetic aspect of the prodrug oxidation and the selectivity of this reaction towards certain ROS from the tumor microenvironment are specified., 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 © 2020 Elsevier Masson SAS. All rights reserved.)

Introduction: Cancer patients are particularly at risk for drug interactions. However, in oncology, this risk has not been studied in depth in France. The main objective of this study was to describe the proportion of drug interactions in patients with lung or digestive cancer., Methods: The drug prescriptions of 93 patients were analyzed from may 27th, 2019 to July 07th, 2019 using two software programs (Thériaque™ and DDI Predictor™) in oncology patients hospitalized in our comprehensive cancer center., Results: Of the 88 patients included in the study, 544 drug interactions were identified, in 66 patients (75.0%, 95% CI: 64.6-83.6). For 20/88 patients (22.7% CI: 14.5-32.9) a non-recommended combination or a theoretical contraindication was reported. Etoposide was the anticancer molecule most involved in combinations that are contraindicated or not recommended. No combinations defined as not recommended or contraindicated were observed in any of the 49 patients treated with chemotherapy during their hospitalization. The most common toxicities were alertness and metabolic disorders, including hyperkalemia. The use of three or more drugs was a risk factor for drug interactions (83 vs. 23%, P<0.001)., Conclusion: Drug interactions remain a major concern in cancer hospitalized patients. It is important to continue and strengthen the collaboration between physicians and pharmacists in order to better prevent their occurrence., (Copyright © 2020 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Since the beginning of COVID-19 pandemic, it is known that the severe course of the disease occurs mostly among the elderly, whereas it is rare among children and young adults. Comorbidities, in particular, diabetes and hypertension, clearly associated with age, besides obesity and smoke, are strongly associated with the need for intensive treatment and a dismal outcome. A weaker immunity of the elderly has been proposed as a possible explanation of this uneven age distribution. Thus, there is concern that children treated for cancer may allso be at risk for an unfavourable course of infection. Along the same line, anecdotal information from Wuhan, China, mentioned a severe course of COVID-19 in a child treated for leukaemia., Aim and Methods: We made a flash survey on COVID-19 incidence and severity among children on anticancer treatment. Respondents were asked by email to fill in a short Web-based survey., Results: We received reports from 25 countries, where approximately 10,000 patients at risk are followed up. At the time of the survey, more than 200 of these children were tested, nine of whom were positive for COVID-19. Eight of the nine cases had asymptomatic to mild disease, and one was just diagnosed with COVID-19. We also discuss preventive measures that are in place or should be taken and treatment options in immunocompromised children with COVID-19., Conclusion: Thus, even children receiving anticancer chemotherapy may have a mild or asymptomatic course of COVID-19. While we should not underestimate the risk of developing a more severe course of COVID-19 than that observed here, the intensity of preventive measures should not cause delays or obstructions in oncological treatment., Competing Interests: Conflict of interest statement The authors have no conflict of interest with regard to this study., (Copyright © 2020. Published by Elsevier Ltd.)

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent complication in patients receiving anticancer chemotherapy, but no effective treatment is yet available. Objective: To evaluate the efficacy and safety of a tramadol/acetaminophen combination tablets for CIPN. Design: This is a single-arm phase II study of tramadol/acetaminophen. Setting/subjects: Eligible patients had received oxaliplatin, paclitaxel, or nab-paclitaxel, and were experiencing CIPN. The patients were given one tablet (37.5 mg tramadol plus 325 mg acetaminophen) twice a day for 7 days, then four times a day for 21 days. Measurements: The primary endpoint was the numerical rating scale of neuropathic pain. Other endpoints included the potential of CYP2D6 genetic variants to effective response or toxicity. Results: Of the 34 patients enrolled, 23 completed the protocol treatment. The mean neuropathic pain score decreased insignificantly from 5.53 at baseline to 5.00 at 28 days (95% confidence interval -0.21 to 1.43; p  = 0.139). However, 13 of the 23 (56.5%) patients who completed the protocol treatment showed improvement of the neuropathic pain score by at least 1 point. No severe adverse events were observed. Tramadol/acetaminophen may be more effective in patients with the intermediate metabolizer phenotype of the CYP2D6 single nucleotide polymorphisms (SNPs) although at the cost of increased toxicity. Conclusions: Although tramadol/acetaminophen tablets did not reduce neuropathic pain to a statistically significant degree, the neuropathic pain severity reduced in more than a half of the patients., Competing Interests: The study was planned, carried out, and analyzed by the authors. No employees of Janssen Pharmaceutical K.K. were involved in these processes., (© Daisuke Naruge et al., 2020; Published by Mary Ann Liebert, Inc.)

Adipose-derived stem cells (ADSCs) primed with paclitaxel (PTX) are now hypothesized to represent a potential Trojan horse to vehicle and deliver PTX into tumors. We analyzed the anticancer activity of PTX released by ADSCs primed with PTX (PTX-ADSCs) (~20 ng/mL) in a panel of ovarian cancer (OvCa) cells sensitive or resistant to PTX. We used two (2D) and three dimensional (3D) in vitro models (multicellular tumor spheroids, MCTSs, and heterospheroids) to mimic tumor growth in ascites. The coculture of OvCa cells with PTX-ADSCs inhibited cell viability in 2D models and in 3D heterospheroids (SKOV3-MCTSs plus PTX-ADSCs) and counteracted PTX-resistance in Kuramochi cells. The cytotoxic effects of free PTX and of equivalent amounts of PTX secreted in PTX-ADSC-conditioned medium (CM) were compared. PTX-ADSC-CM decreased OvCa cell proliferation, was more active than free PTX and counteracted PTX-resistance in Kuramochi cells (6.0-fold decrease in the IC50 values). Cells cultivated as 3D aggregated MCTSs were more resistant to PTX than 2D cultivation. PTX-ADSC-CM (equivalent-PTX) was more active than PTX in MCTSs and counteracted PTX-resistance in all cell lines. PTX-ADSC-CM also inhibited OvCa-MCTS dissemination on collagen-coated wells. In conclusion, PTX-ADSCs and PTX-MSCs-CM may represent a new option with which to overcome PTX-resistance in OvCa., Competing Interests: The authors declare no conflict of interest.

This study describes the synthesis of arylboronate-based ROS-responsive prodrugs of doxorubicin and their biological evaluation as anticancer agents. The determination of the most sensitive cancer type toward arylboronate prodrugs is crucial for further consideration of these molecules in clinical phase. To address this goal, an arylboronate-based profluorescent probe was used to compare the capacity of various cancer cell lines to efficiently convert the precursor into the free fluorophore. On the selected MiaPaCa-2 pancreatic cancer cells, a benzeneboronate prodrug exhibited 67% of the cytotoxicity obtained with the free doxorubicin. The prodrug was also able to induce tumor regression on MiaPaCa-2 pancreatic tumor model in ovo. Using this model, the amount of free doxorubicin liberated from this prodrug into the tumor was equivalent to the quantity measured after direct intratumoral injection of the same concentration of doxorubicin., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: The perceptions that postgraduate medical students have about cancer and chemotherapy could have an impact on the quality of their interactions with their future patients. We conducted this study in order to highlight their representational field for chemotherapy and cancer., Method: From February 1st to May 31st 2018, 618 students from the 3rd cycle in medical studies from Saint-Thomas d'Aquin University and Ouaga I Pr Joseph Ki-Zerbo of the city of Ouagadougou took part in the study. They were given self-administered questionnaire, which include a collection of free and hierarchical evocations in response to the inducers "cancer" and "chemotherapy". They were also asked to propose arguments to convince and gain trust of a fictitious patient waiting for chemotherapy., Results: The fatal aspect of cancer was largely present in their representational world. The representational field of chemotherapy was related to the side effects and the expensive aspect of anticancer drugs. In spite of a negative representation of cancer, students were able to find words with positive connotations to convince patients waiting for chemotherapy to follow treatment., Discussion: Knowing these representations makes it possible to understand the stakes of the doctor-patient relationship in order to improve the training of future doctors, as well as the care of patients., (Copyright © 2019 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

DDX3X is an ATPase/RNA helicase of the DEAD-box family and one of the most multifaceted helicases known up to date, acting in RNA metabolism, cell cycle control, apoptosis, stress response and innate immunity. Depending on the virus or the viral cycle stage, DDX3X can act either in a proviral fashion or as an antiviral factor. Similarly, in different cancer types, it can act either as an oncogene or a tumor-suppressor gene. Accumulating evidence indicated that DDX3X can be considered a promising target for anticancer and antiviral chemotherapy, but also that its exploitation requires a deeper understanding of the molecular mechanisms underlying its dual role in cancer and viral infections. In this Review, we will summarize the known roles of DDX3X in different tumor types and viral infections, and the different inhibitors available, illustrating the possible advantages and potential caveats of their use as anticancer and antiviral drugs.

Purpose: There is no consensus on how to handle complex drug combinations of cancer drugs through medico-administrative databases. Our objective was to develop an algorithm for identifying the nature and patterns of treatment lines in a cohort of newly treated multiple myeloma patients., Methods: A cohort of multiple myeloma patients starting a first treatment line was built using both ambulatory and hospital data from regional data of the French national healthcare system database (SNIIRAM). Patients were identified from January 2011 to September 2013 using ICD-10 codes for multiple myeloma ('C90') within long-term conditions or diagnosis from hospital data. Drugs of interest for cycle identification included bortezomib, imids (thalidomide, lenalidomide), alkylating drugs (cyclophosphamide, melphalan, bendamustine, doxorubicin) and dexamethasone. An algorithm was applied to define combinations of treatment received in the first 6 months of treatment., Results: Among the 236 patients included, 45% received bortezomib-melphalan-prednisone (VMP: n = 107), 22% bortezomib-thalidomide-dexamethasone (VTD/VTD-PACE: n = 52) and 21% melphalan-prednisone-thalidomide (MPT: n = 49). Other drug regimens consisted in melphalan-prednisone (MP: 7%, n = 17), lenalidomide-dexamethasone (RD) (4%, n = 9), bortezomib-cyclophosphamide-dexamethasone (VCD: n = 1) and bortezomib-bendamustine-dexamethasone (VBD: n = 1). Type of drug regimens and allocation by age class (±65 years) were in accordance with current recommendations., Conclusions: This study demonstrates the feasibility of identifying complex drug regimens in onco-haematology, using both outpatient and inpatient drug records in French health insurance databases., (Copyright © 2017 John Wiley & Sons, Ltd.)

Some anticancer agents induce immunogenic cell death that is accompanied by the emission of danger signals into the tumor microenvironment, thus attracting and activating innate immune effectors and finally inducing anticancer immunity. The release of extracellular nucleosides such as adenosine triphosphate (ATP) from the tumor in response to anticancer therapy plays a pivotal role in the attraction of antigen presenting cells and the activation of inflammasome-mediated proinflammatory cascades. In contrast, the ectonucleotidase-catalyzed phosphohydrolysis of nucleotides to nucleosides reduces the extracellular availability of nucleotides, hence limiting the recruitment and activation of antigen-presenting cells. In addition, the (over-)production of nucleosides including adenosine by ectonucleotidases located on cancer cells and regulatory T cells can induce immunosuppression, as adenosine directly inhibits the proliferation and activation of effector T cells. Here, we discuss the importance of death metabolites for immunomodulation in general, and the role of the purine nucleotide ATP and its derivative adenosine in particular. In addition, we provide an overview on therapeutic interventions that reinstate tumor immunogenicity in conditions where nucleotide-dependent immunostimulation is obstructed., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Lung cancer is a leading cause of cancer-related death, and patients with lung cancer are a priority group for influenza vaccination. However, few studies have assessed the immunogenicity of the influenza vaccine in these patients. Here, we performed a prospective study to evaluate the immunogenicity of the influenza vaccine in patients with lung cancer undergoing anticancer chemotherapy. Twenty-five patients with lung cancer undergoing anticancer chemotherapy and 26 patients with chronic obstructive pulmonary disease (COPD) as controls were enrolled. A trivalent influenza vaccine containing inactivated A/California/7/2009 (H1N1) pdm09, A/Texas/50/2012 (H3N2), and B/Massachusetts/2/2012 was administered as a single subcutaneous injection. Serum samples were collected before vaccination, and at 4-6 weeks after vaccination. Levels of serum antibody to hemagglutinin were measured. Among patients with lung cancer, the seroprotection rate (postvaccination titer > 1:40) was 84% for both A(H1N1) and A(H3N2), similar to the levels observed in patients with COPD. However, the seroprotection rate for the B strain was significantly lower in patients with lung cancer than in patients with COPD (64% versus 92%). Even after adjustment for potential confounders, patients with lung cancer had a significantly lower odds ratio for seroprotection against the B strain than patients with COPD. Moreover, in patients with lung cancer, those receiving the platinum doublet treatment tended to exhibit a lower seroprotection rate than those receiving a single agent. Thus, patients with lung cancer undergoing anticancer chemotherapy showed acceptable immune responses to a trivalent influenza vaccine, supporting the recommendation for annual influenza vaccination in these patients.

Targeting heparan sulfate proteoglycans (HSPGs) and enzymes involved in heparan sulfate (HS) chain editing is emerging as a new anticancer strategy. The involvement of HSPGs in tumor cell signaling, inflammation, angiogenesis and metastasis indicates that agents able to inhibit aberrant HSPG functions can potentially act as multitarget drugs affecting both tumor cell growth and the supportive boost provided by the microenvironment. Moreover, accumulating evidence supports that an altered expression or function of HSPGs, or of the complex enzyme system regulating their activities, can also depress the tumor response to anticancer treatments in several tumor types. Thereby, targeting HSPGs or HSPG modifying enzymes appears an appealing approach to enhance chemotherapy efficacy. A great deal of effort from academia and industry has led to the development of agents mimicking HS, and/or inhibiting HSPG modifying enzymes. Inhibitors of Sulf-2, an endosulfatase that edits the HS sulfation pattern, and inhibitors of heparanase, the endoglycosidase that produces functional HS fragments, appear particularly promising. In fact, a Sulf-2 inhibitor (OKN-007), and two heparanase inhibitors/HS mimics (roneparstat, PG545) are currently under early clinical investigation. In this review, we summarized preclinical studies in experimental tumor models of the main chemical classes of Sulf-2 and heparanase inhibitors. We described examples of different mechanisms through which heparanase and HSPGs, often in cooperation, may impact tumor sensitivity to various antitumor agents. Finally, we reported a few preclinical studies showing increased antitumor efficacy obtained with the use of candidate clinical HS mimics in combination regimens., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Colon cancer is a leading cause of cancer-related death in humans. 5-Fluorouracil (5-FU), a major chemotherapy treatment, has been used for decades to fight numerous types of cancers, including breast, colon, and head and neck carcinomas. Unfortunately, a large proportion of patients treated with 5-FU develop toxicities that include diarrhea, mucositis, neutropenia, and vomiting. While the side effects of 5-FU are well known, the mechanisms underlying the induction of these unpleasant symptoms are poorly understood. The study by McQuade et al. in this issue of Neurogastroenterology & Motility provides important new potential explanations for the gastrointestinal (GI) dysfunction induced by 5-FU. These researchers carefully investigated an overlooked research area in which the symptoms of GI-motility dysfunction maybe due to an effect on the enteric nervous system. McQuade et al. delivered 5-FU treatment to mice and discovered an initial increase in GI transit (associated with acute intestinal inflammation), followed by a slowing in transit. Major differences were noted in characteristics of colonic migrating motor complexes. These effects maybe causally related to deficits in enteric ganglia or neurotransmission. Their study identified specific neurochemical classes of neurons in the myenteric plexus most affected by 5-FU. This is the first study to provide evidence that the functional intrinsic neural pathways within the enteric nervous system are likely impaired by 5-FU, leading to colonic dysmotility. This review will describe major patterns of motor activity in isolated whole mouse colon and how these patterns are modified by anticancer chemotherapy., (© 2016 John Wiley & Sons Ltd.)

Restoration of the p53 pathway, namely by reactivation of mutant (mut) p53, represents a valuable anticancer strategy. Herein, we report the identification of the enantiopure tryptophanol-derived oxazoloisoindolinone SLMP53-1 as a novel reactivator of wild-type (wt) and mut p53, using a yeast-based screening strategy. SLMP53-1 has a p53-dependent anti-proliferative activity in human wt and mut p53R280K-expressing tumor cells. Additionally, SLMP53-1 enhances p53 transcriptional activity and restores wt-like DNA binding ability to mut p53R280K. In wt/mut p53-expressing tumor cells, SLMP53-1 triggers p53 transcription-dependent and mitochondrial apoptotic pathways involving BAX, and wt/mut p53 mitochondrial translocation. SLMP53-1 inhibits the migration of wt/mut p53-expressing tumor cells, and it shows promising p53-dependent synergistic effects with conventional chemotherapeutics. In xenograft mice models, SLMP53-1 inhibits the growth of wt/mut p53-expressing tumors, but not of p53-null tumors, without apparent toxicity. Collectively, besides the potential use of SLMP53-1 as anticancer drug, the tryptophanol-derived oxazoloisoindolinone scaffold represents a promissing starting point for the development of effective p53-reactivating drugs.

Objectives: The aims of this study were to clarify the frequency and prognosis of febrile neutropenia (FN) in patients who received urological anticancer chemotherapy., Methods: Between May 2005 and January 2010, 141 patients underwent urological anticancer chemotherapy at the Sapporo Medical University Hospital, Sapporo, Japan. They consisted of 124 men and 17 women aged 62 (range 16-80) years. The patients underwent a total of 626 treatment courses of urological anticancer chemotherapy., Results: Of the 626 urological anticancer chemotherapy courses, grades 3 and 4 neutropenia occurred in 451 (72.0 %) courses. FN developed in 57 (9.1 %) courses in which 7 (12.3 %) and 50 (87.7 %) patients were classified as high risk and low risk, respectively, according to the Multinational Association for Supportive Care in Cancer (MASCC) risk index scoring system. There was no anticancer chemotherapy-related death in either the high- or low-risk group. The frequencies of bacteria isolated from courses with FN were 0 and 10.0 % for the high- and low-risk groups, respectively., Conclusions: According to the MASCC scoring system, there were fewer patients in the high-risk group than in the low-risk group in this study. There were no cases of anticancer chemotherapy-related death in either group. Therefore, urological anticancer chemotherapy can be conducted safely with the proper management of neutropenia and FN.

Thrombocytopenia is a major complication of liver cirrhosis that often limits the use of anticancer drugs. In this report, we describe a thrombocytopenic patient with liver cirrhosis who developed pancreatic tail cancer and underwent splenic irradiation. Particular emphasis was placed on the impact of irradiation on thrombocytopenia. A 73-year-old male with liver cirrhosis was diagnosed with pancreatic tail cancer infiltrating the splenic hilum by computed tomography (CT) and pancreatic juice cytology. His baseline platelet count was 84 × 10(3)/mm(3). A total of 50 Gy of irradiation to the pancreatic tail and splenic hilum was carried out as local therapy for pancreatic cancer. Splenic irradiation was also expected to reverse liver cirrhosis-related thrombocytopenia, which was making systemic chemotherapy difficult to administer in this patient. One month later, systemic gemcitabine chemotherapy was commenced. At the start of chemotherapy, his platelet count remained at 93 × 10(3)/mm(3), but rose to 246 × 10(3)/mm(3) 2.5 months later, which allowed the administration of chemotherapy without any remarkable hematologic toxicities. Post-irradiation CT revealed a low density area indicating irradiation-induced necrotic tissue that had expanded into the surrounding non-tumorous spleen parenchyma, and which may have impacted positively on the thrombocytopenia. Our case report suggests that splenic irradiation may be a potential therapeutic option for liver cirrhosis-related thrombocytopenia, especially in patients who require systemic chemotherapy for cancer.