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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.

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. [ABSTRACT FROM AUTHOR]

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.

A 51-year-old woman was admitted to our hospital because of pneumonia after chemotherapy with doxorubicin and cyclophosphamide for left breast cancer. The patient was diagnosed with Mycobacterium abscessus pulmonary infection by the detection of M. abscessus complex (MABC) in sputum cultures. However, MABC is intrinsically resistant to most of the antibacterial agents, and MABC pulmonary disease outcomes with modern antibiotic treatment are currently the worst among all mycobacterial species. We herein report the successful treatment of M. abscessus pulmonary infection by a combination treatment with antibiotics and surgical lung resection.

Introduction: Polypharmacy increases hazard of drug-drug interactions(DDIs), hospitalization, treatment toxicity, and mortality in elderly individuals with cancer. The present study explores and analyzes prevalence and severity of DDIs in geriatric cancer patients subjected to anticancer chemotherapy, their mechanisms, stratification of severity, and correlation between DDI risk and number of medications taken. Methods: This was a cross-sectional study conducted between January-July 2019 at the Medical Oncology/Hematology and Radiation-Oncology Departments, All India Institute of Medical Sciences(AIIMS) Rishikesh. The study included a convenience sampling of 126 geriatric cancer patients. Results: 126 patients were enrolled in present study. DDIs were identified in 97.6% of elderly cancer patients, and 88.9% had at least one DDI with antineoplastic medications. Highest number of DDIs involving antineoplastic medications in any given patient was 12. DDIs involving medications used for treatment of non-cancerous diseases were observed in 83.3% of patients; highest number of interactions identified in any given patient was 15. Out of 473 interactions, 237(50.1%) DDIs were attributable to pharmacodynamic mechanisms of action. 126(27%) of DDIs involved pharmacokinetic mechanisms and 110(23.6%) involved unknown mechanisms. In this present study, total number of DDIs could be positively correlated with total number of medications and number of health problems. Conclusions: Geriatric cancer patients are at high risk of DDIs ascribable to polypharmacy. Physicians may utilize online DDI checking softwares to alert themselves, characterize potential DDIs, and modify medications judiciously. An integrative and algorithmic approach with inclusion of geriatricians, oncologists, cardiologists, general practitioners, and clinical pharmacologists/ pharmacists is imperative to optimize drug therapy.

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.)

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.

Trois types de médicaments anticancéreux systémiques sont utilisés pour traiter les cancers du sein, la chimiothérapie cytotoxique, l'hormonothérapie et les thérapies ciblées, d'usage plus récent. L'équipe officinale doit maîtriser les notions essentielles concernant ces traitements pour assurer une dispensation de qualité. Three types of systemic anticancer drugs are used for the treatment of breast cancer, cytotoxic chemotherapy, hormone therapy and targeted therapies, of more recent use. The pharmacy team must be familiar with the basics of these treatments to ensure quality dispensing. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. • Flash survey was used to get data on COVID-19 incidence and severity. • Paediatric haematology/oncology departments of 25 countries responded. • COVID-19 may have a mild course in these immunocompromised children. • Precautions should be taken to prevent any infections including COVID-19. • Malignancy is a primary danger; preventive measures should not hinder its treatment. [ABSTRACT FROM AUTHOR]

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.

Cancer which caused by the growth and spreading of abnormal cells in an uncontrolled manner remains a major cause of death affecting millions of people. The current cancer chemotherapy treatment modalities have several disadvantages, mostly related to their undesirable side effects. In this study, we explore the potencies of selected cell penetrating antimicrobial peptides in combination with the widely used chemotherapy drug, Doxorubicin (DOX), to increase the specificity of anticancer chemotherapy. Screening the potential peptide candidates to be developed into chemotherapy drug combination led to identification of two most potent peptides, Tachyplesin 1 (TCH) and Latarcin 1 (LTC). Cell viability of normal liver cells was reduced to 50% by 20 µM of TCH or LTC, while liver cancer cell lines lost 50% of their viability at approximately 4 µM of these peptides. The combination of DOX with TCH peptide showed the higher levels of lactate dehydrogenase (LDH) leakage from cancer cells (80%) compared to normal cells (30%). The combinational treatment DOX-peptide showed significant (P < 0.01) increase in caspase 3/7 activity compared to DOX alone. Pre-treatment of the cells with TCH peptides prior to DOX treatment considerably increased the Caspase 3/7 activities in both cell types with significant increase (P < 0.05) in cancer cells compared to normal cells. Our study demonstrate that TCH peptide is a potential anticancer peptide that could be used in combinational therapy with cancer chemotherapy drugs. [ABSTRACT FROM AUTHOR]

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.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 (NanoCyss) of tens of nanometers in size in aqueous media. The stability of NanoCyss 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 NanoCyss were also analyzed using DLS measurements by changing the pH and NaCl concentration. NanoCyss 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 NanoCyss to the tumor xenograft mouse model successfully suppressed tumor growth. Interestingly, this effect depended on the MW of the PCys segments. [Display omitted] • Poly(cysteine)-based nanoparticles (NanoCys) were developed as a new antioxidant. • NanoCys was a stable sphere in water under physiological conditions. • NanoCys were less toxic than N -acetyl Cys against both cancer and normal cells. • NanoCys suppressed tumor growth on a xenograft mouse model of colon-26 cells. • The anticancer effect was varied by the molecular weight of poly(cysteine). [ABSTRACT FROM AUTHOR]

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.

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. [ABSTRACT FROM AUTHOR]

Resistance to chemotherapy in cancer cells is mainly mediated by overexpression of P-glycoprotein (Pgp), a plasma membrane ATP-binding cassette (ABC) transporter which extrudes cytotoxic drugs at the expense of ATP hydrolysis. Pgp consists of two homologous halves each containing a transmembrane domain and a cytosolic nucleotide-binding domain (NBD) which contains two consensus Walker motifs, A and B, involved in ATP binding and hydrolysis. The protein also contains an S signature characteristic of ABC transporters. The molecular mechanism of Pgp-mediated drug transport is not known. Since the transporter has an extraordinarily broad substrate specificity, its cellular function has been described as a "hydrophobic vacuum cleaner". The limited knowledge about the mechanism of Pgp, partly due to the lack of a high-resolution structure, is well reflected in the failure to efficiently inhibit its activity in cancer cells and thus to reverse multidrug resistance (MDR). In contrast to the difficulties encountered when studying the full-length Pgp, the recombinant NBDs can be obtained in large amounts as soluble proteins. The biochemical and biophysical characterization of recombinant NBDs is shown here to provide a suitable alternative route to establish structure-function relationships. NBDs were shown to bind ATP and analogues as well as potent modulators of MDR, such as hydrophobic steroids, at a region close to the ATP site. Interestingly, flavonoids also bind to NBDs with high affinity. Their binding site partly overlaps both the ATP-binding site and the steroid-interacting region. Therefore flavonoids constitute a new promising class of bifunctional modulators of Pgp.