An overlooked risk for skin health: Less availability and higher cost of sunscreen for people with melanated skin.

Background: Sunscreen with a skin protection factor (SPF) of 30 or greater is recommended to reduce the risk of skin cancer and improve skin health for all people regardless of skin tone. Traditional sunscreen that creates a white cast on the skin is incompatible with melanated skin. Methods: The number of products on the shelf, SPF level, application, coloration, and cost were recorded at three beauty supply chain stores and three pharmacy, health, and wellness stores in or near Harlem in New York City in the Spring of 2023. The number of skin tones for tinted sunscreen was visually matched to the Fitzpatrick Skin Phototypes scale. Results: A total of 385 sunscreen products were identified; 78.7 % were traditional white sunscreen, followed by sheer (15.3 %) and tinted (6.0 %) products. Beauty supply stores offered more tinted sunscreen options than did pharmacy, health, and wellness stores (n = 17,15.3 % vs. n = 6, 2.2 %, p < 0.001). Of the tinted sunscreen products, 19 brands offered only a single tone. Tinted sunscreen was significantly more expensive with an average cost of $24.59 [SD $14.71] per ounce vs. $6.85 [SD 8.66] for traditional, and $9.38 [SD 8.92] for sheer suncreen. Conclusions: Sunscreen that is tinted or sheer and compatible with melanated skin is less available and more costly than traditional white sunscreen in beauty and pharmacy chain stores in NYC. Availability and affordability of sunscreen matching the spectrum of skin tones are essential for optimal sun protection and skin health.

Comparative proteomics of a versatile, marine, iron-oxidizing chemolithoautotroph.

This study conducted a comparative proteomic analysis to identify potential genetic markers for the biological function of chemolithoautotrophic iron oxidation in the marine bacterium Ghiorsea bivora. To date, this is the only characterized species in the class Zetaproteobacteria that is not an obligate iron-oxidizer, providing a unique opportunity to investigate differential protein expression to identify key genes involved in iron-oxidation at circumneutral pH. Over 1000 proteins were identified under both iron- and hydrogen-oxidizing conditions, with differentially expressed proteins found in both treatments. Notably, a gene cluster upregulated during iron oxidation was identified. This cluster contains genes encoding for cytochromes that share sequence similarity with the known iron-oxidase, Cyc2. Interestingly, these cytochromes, conserved in both Bacteria and Archaea, do not exhibit the typical ß-barrel structure of Cyc2. This cluster potentially encodes a biological nanowire-like transmembrane complex containing multiple redox proteins spanning the inner membrane, periplasm, outer membrane, and extracellular space. The upregulation of key genes associated with this complex during iron-oxidizing conditions was confirmed by quantitative reverse transcription-PCR. These findings were further supported by electromicrobiological methods, which demonstrated negative current production by G. bivora in a three-electrode system poised at a cathodic potential. This research provides significant insights into the biological function of chemolithoautotrophic iron oxidation.

E-cigarettes and arrhythmogenesis: a comprehensive review of pre-clinical studies and their clinical implications.

Electronic cigarette use has grown exponentially in recent years, and while their popularity has increased, the long-term effects on the heart are yet to be fully studied and understood. Originally designed as devices to assist with those trying to quit traditional combustible cigarette use, their popularity has attracted use by teens and adolescents who traditionally have not smoked combustible cigarettes. Acute effects on the heart have been shown to be similar to traditional combustible cigarettes, including increased heart rate and blood pressure. The main components of electronic cigarettes that contribute to these arrhythmic effects are found in the e-liquid that is aerosolized and inhaled, comprised of nicotine, flavourings, and a combination of vegetable glycerin (VG) and propylene glycol (PG). Nicotine can potentially induce both ventricular and atrial arrhythmogenesis, with both the atrial and ventricular effects resulting from the interactions of nicotine and the catecholamines they release via potassium channels. Atrial arrhythmogenesis, more specifically atrial fibrillation, can also occur due to structural alterations, which happens because of nicotine downregulating microRNAs 133 and 590, both post-transcriptional growth factor repressors. Liquid flavourings and the combination of PG and VG can possibly lead to arrhythmic events by exposing users to acrolein, an aldehyde that stimulates TRPA1 that in turn causes a change towards sympathetic activation and autonomic imbalance. The design of these electronic delivery devices is constantly changing; therefore, it has proven extremely difficult to study the long-term effects on the heart caused by electronic cigarettes but will be important to understand given their rising popularity. The arrhythmic effects of electronic cigarettes appear similar to traditional cigarettes as well; however, a comprehensive review has not been compiled and is the focus of this article.

The past, present, and future of immunotherapy for endometrial adenocarcinoma.

Incidences of endometrial adenocarcinoma are increasing in the USA with poor prognosis for patients with advanced disease. The current treatment standard is surgery including total hysterectomy and bilateral oophorectomy with surgical staging and adjunct treatment, such as chemotherapy or radiation. However, these methods do not present as an effective treatment option for poorly differentiated advanced cancers. Advancements in immunotherapy now offer a new approach for various types of cancer and specifically show promise in the treatment of endometrial adenocarcinoma. This review summarizes immunotherapeutic treatment options relevant to endometrial adenocarcinoma, such as immune checkpoint blockades, bispecific T-cell engager antibodies, vaccinations, and adoptive cell transfer. This study could be helpful for clinicians to identify treatment options more suitable for women with late-stage endometrial adenocarcinoma.

The past, present, and future of immunotherapy for bladder tumors.

Bladder cancer is a prominent cancer worldwide with a relatively low survival rate for patients with increased stage and metastasis. Current treatments are based on surgical removal, bacillus Calmette-Guerin (BCG) Immunotherapy, and platinum-based chemotherapy. However, treatment resistance due to genetic instability of bladder tumors, as well as intolerance to treatment adverse effects leads to the necessity to further treatment options. New advancements in immunotherapy are on the rise for treatment of various cancers and specifically has shown promise in the treatment of bladder cancer. This review summarizes these new advancements in treatment options involving cytokines and cytokine blockade. Such a study might be helpful for urologists to manage patients with bladder cancer more effectively.

A Genus Definition for Bacteria and Archaea Based on a Standard Genome Relatedness Index.

Genus assignment is fundamental in the characterization of microbes, yet there is currently no unambiguous way to demarcate genera solely using standard genomic relatedness indices. Here, we propose an approach to demarcate genera that relies on the combined use of the average nucleotide identity, genome alignment fraction, and the distinction between type- and non-type species. More than 3,500 genomes representing type strains of species from >850 genera of either bacterial or archaeal lineages were tested. Over 140 genera were analyzed in detail within the taxonomic context of order/family. Significant genomic differences between members of a genus and type species of other genera in the same order/family were conserved in 94% of the cases. Nearly 90% (92% if polyphyletic genera are excluded) of the type strains were classified in agreement with current taxonomy. The 448 type strains that need reclassification directly impact 33% of the genera analyzed in detail. The results provide a first line of evidence that the combination of genomic indices provides added resolution to effectively demarcate genera within the taxonomic framework that is currently based on the 16S rRNA gene. We also identify the emergence of natural breakpoints at the genome level that can further help in the circumscription of taxa, increasing the proportion of directly impacted genera to at least 43% and pointing at inaccuracies on the use of the 16S rRNA gene as a taxonomic marker, despite its precision. Altogether, these results suggest that genomic coherence is an emergent property of genera in Bacteria and ArchaeaIMPORTANCE In recent decades, the taxonomy of Bacteria and Archaea, and therefore genus designation, has been largely based on the use of a single ribosomal gene, the 16S rRNA gene, as a taxonomic marker. We propose an approach to delineate genera that excludes the direct use of the 16S rRNA gene and focuses on a standard genome relatedness index, the average nucleotide identity. Our findings are of importance to the microbiology community because the emergent properties of Bacteria and Archaea that are identified in this study will help assign genera with higher taxonomic resolution.

Quantitative analysis of O2 and Fe2+ profiles in gradient tubes for cultivation of microaerophilic Iron(II)-oxidizing bacteria.

The classical approach for the cultivation of neutrophilic microaerophilic Fe(II)-oxidizing bacteria is agar-based gradient tubes where these bacteria find optimal growth conditions in opposing gradients of oxygen (O2) and dissolved Fe(II) (Fe2+). The goals of this study were to quantify the temporal development of O2 and Fe2+ concentrations over time, to compare abiotic and microbially inoculated tubes and to test the suitability of different Fe(II)-sources for the cultivation of freshwater and marine microaerophilic Fe(II)-oxidizers. O2 and Fe2+ gradients were monitored on a high spatial resolution as a function of time applying amperometric and voltammetric microsensors. Fe(II)-oxidizers could be cultivated well with FeS and zero-valent iron powder as Fe(II)-source, but FeCO3 and FeCl2 are extremely sensitive for this application. Fe(III) minerals accumulated in inoculated tubes within the first days in regions with an O2 concentration of 20-40 µM and were confirmed to be related to bacterial growth. Microbial Fe(II) oxidation could compete only for the first days with the abiotic reaction after which heterogeneous Fe(II) oxidation, catalyzed by Fe(III) minerals, dominated. Our results imply that transfer of cultures to fresh tubes within 48-72 h is crucial to provide optimal growth conditions for microaerophilic Fe(II)-oxidizers, particularly for the isolation of new strains.

The role of microaerophilic Fe-oxidizing micro-organisms in producing banded iron formations.

Despite the historical and economic significance of banded iron formations (BIFs), we have yet to resolve the formation mechanisms. On modern Earth, neutrophilic microaerophilic Fe-oxidizing micro-organisms (FeOM) produce copious amounts of Fe oxyhydroxides, leading us to wonder whether similar organisms played a role in producing BIFs. To evaluate this, we review the current knowledge of modern microaerophilic FeOM in the context of BIF paleoenvironmental studies. In modern environments wherever Fe(II) and O2 co-exist, microaerophilic FeOM proliferate. These organisms grow in a variety of environments, including the marine water column redoxcline, which is where BIF precursor minerals likely formed. FeOM can grow across a range of O2 concentrations, measured as low as 2 µm to date, although lower concentrations have not been tested. While some extant FeOM can tolerate high O2 concentrations, many FeOM appear to prefer and thrive at low O2 concentrations (~3-25 µm). These are similar to the estimated dissolved O2 concentrations in the few hundred million years prior to the 'Great Oxidation Event' (GOE). We compare biotic and abiotic Fe oxidation kinetics in the presence of varying levels of O2 and show that microaerophilic FeOM contribute substantially to Fe oxidation, at rates fast enough to account for BIF deposition. Based on this synthesis, we propose that microaerophilic FeOM were capable of playing a significant role in depositing the largest, most well-known BIFs associated with the GOE, as well as afterward when global O2 levels increased.

Metodologia da análise seminal para pacientes azoospérmicos no laboratório fleury / Methodology of seminal analysis for azoospermicos patients in the laboratório fleury

A azoospermia é definida como a ausência de espermatozoide no líquido seminal ejaculado pelo homem depois de aplicada a técnica de centrifugação em pelo menos duas amostras. Dada a importância de um diagnóstico correto da análise seminal para os casais, toda amostra que não apresentar espermatozoides no exame a fresco deve seguir em avaliação laboratorial. Com isso, o presente estudo tem como objetivo analisar os resultados de centrifugação de uma alíquota do sêmen ejaculado ou de todo o volume ejaculado de pacientes com diagnóstico de azoospermia para determinar qual o melhor método a ser empregado na análise seminal para esse grupo de pacientes.

The azoospermia is defined as the absence of sperm in the ejaculate by the seminal fluid man after centrifugation technique conducted in at least two samples. Given the importance of a correct diagnosis of the seminal analysis for couples, all sample no sperm present in fresh examination should follow in laboratory tests. Thus the present study aims to analyze the results of a spin rate of ejaculate or all of the ejaculate volume of patients with azoospermia to determine the best method to be used in semen analysis for this group of patients.

Negative pressure wound therapy for sternal wound infections following congenital heart surgery.

OBJECTIVE: This study examines the efficacy of a comprehensive, multidisciplinary wound management team and negative pressure wound therapy (NPWT) for the treatment of sternal wound infections in congenital heart surgery patients. METHOD: A single-institution retrospective review of all congenital heart surgery patients with post-operative sternal wound infections who were treated with NPWT was performed. Patients were evaluated based on (a) whether NPWT occurred before or after the establishment of a multidisciplinary wound management team, and (b) whether NPWT was initiated early (within 2 days) or late (greater than 2 days) after diagnosis of a sternal wound infection. RESULTS: The median duration of NPWT was 12 days (range 2-50 days). NPWT was successfully initiated in patients as young as 15 days of age. There was a trend toward shorter duration of both NPWT and antibiotic use following (a) the implementation of the multidisciplinary wound management team, and (b) in patients with early use of NPWT; however, these results did not achieve statistical significance. CONCLUSION: NPWT can be successfully utilised in congenital heart surgery patients, including young neonates, for the treatment of sternal wound infections. The trends observed in the reduction of wound therapy duration and antibiotic duration with early implementation of negative pressure therapy and multidisciplinary wound management require further investigation to verify their clinical efficacy in patient care.

Morphology of biogenic iron oxides records microbial physiology and environmental conditions: toward interpreting iron microfossils.

Despite the abundance of Fe and its significance in Earth history, there are no established robust biosignatures for Fe(II)-oxidizing micro-organisms. This limits our ability to piece together the history of Fe biogeochemical cycling and, in particular, to determine whether Fe(II)-oxidizers played a role in depositing ancient iron formations. A promising candidate for Fe(II)-oxidizer biosignatures is the distinctive morphology and texture of extracellular Fe(III)-oxyhydroxide stalks produced by mat-forming microaerophilic Fe(II)-oxidizing micro-organisms. To establish the stalk morphology as a biosignature, morphologic parameters must be quantified and linked to the microaerophilic Fe(II)-oxidizing metabolism and environmental conditions. Toward this end, we studied an extant model organism, the marine stalk-forming Fe(II)-oxidizing bacterium, Mariprofundus ferrooxydans PV-1. We grew cultures in flat glass microslide chambers, with FeS substrate, creating opposing oxygen/Fe(II) concentration gradients. We used solid-state voltammetric microelectrodes to measure chemical gradients in situ while using light microscopy to image microbial growth, motility, and mineral formation. In low-oxygen (2.7-28 µm) zones of redox gradients, the bacteria converge into a narrow (100 µm-1 mm) growth band. As cells oxidize Fe(II), they deposit Fe(III)-oxyhydroxide stalks in this band; the stalks orient directionally, elongating toward higher oxygen concentrations. M. ferrooxydans stalks display a narrow range of widths and uniquely biogenic branching patterns, which result from cell division. Together with filament composition, these features (width, branching, and directional orientation) form a physical record unique to microaerophilic Fe(II)-oxidizer physiology; therefore, stalk morphology is a biosignature, as well as an indicator of local oxygen concentration at the time of formation. Observations of filamentous Fe(III)-oxyhydroxide microfossils from a ~170 Ma marine Fe-Si hydrothermal deposit show that these morphological characteristics can be preserved in the microfossil record. This study demonstrates the potential of morphological biosignatures to reveal microbiology and environmental chemistry associated with geologic iron formation depositional processes.

Lattice Boltzmann simulation of nonequilibrium effects in oscillatory gas flow.

Accurate evaluation of damping in laterally oscillating microstructures is challenging due to the complex flow behavior. In addition, device fabrication techniques and surface properties will have an important effect on the flow characteristics. Although kinetic approaches such as the direct simulation Monte Carlo (DSMC) method and directly solving the Boltzmann equation can address these challenges, they are beyond the reach of current computer technology for large scale simulation. As the continuum Navier-Stokes equations become invalid for nonequilibrium flows, we take advantage of the computationally efficient lattice Boltzmann method to investigate nonequilibrium oscillating flows. We have analyzed the effects of the Stokes number, Knudsen number, and tangential momentum accommodation coefficient for oscillating Couette flow and Stokes' second problem. Our results are in excellent agreement with DSMC data for Knudsen numbers up to Kn=O(1) and show good agreement for Knudsen numbers as large as 2.5. In addition to increasing the Stokes number, we demonstrate that increasing the Knudsen number or decreasing the accommodation coefficient can also expedite the breakdown of symmetry for oscillating Couette flow. This results in an earlier transition from quasisteady to unsteady flow. Our paper also highlights the deviation in velocity slip between Stokes' second problem and the confined Couette case.

Biologia e preferência alimentar de Ascia monuste orseis (Latreille) (Lepidoptera: Pieridae) na planta invasora Raphanus raphanistrum L / Biology and feeding preference of Ascia monuste orseis (Latreille) (Lepidoptera: Pieridae) on the weed Raphanus raphanistrum L

Foi estudada a biologia e preferência alimentar do curuquerê-da-couve, Ascia monuste orseis (Latreille) na planta invasora R. raphanistrum L. Ovos de A. monuste orseis foram coletados nas plantas de couve manteiga da fazenda da Universidade Estadual de Londrina (UEL), PR. As lagartas foram individualizadas, recebendo folhas de nabiça diariamente, observando-se os ínstares e registrando-se a mortalidade. A duração média da fase larval foi de 12,9 (± 0,08) dias, com mortalidade de 42,0 por cento; a duração média da fase pupal foi 6,7 (±0,13) dias e a mortalidade de 38,4 por cento. O curuquerê preferiu alimentar-se de nabiça, comparativamente com a couve manteiga, Brassica oleracea var. acephala.

The biology and feeding preference of the kale leafworm, Ascia monuste orseis (Latreille) on the weed Raphanus raphanistrum Godart was studied. Eggs were collected on plants at the farm of the Universidade Estadual de Londrina (UEL), PR, Brazil. Neonate caterpillars were individualized and were daily fed on leaves of R. raphanistrum; instar duration and mortality were recorded. Mean duration of the larval stage was 12.9 (± 0.08) days and mortality was 42.0 percent. Mean duration of the pupal stage was 6.7 (± 0.13) days, and mortality was 38.4 percent. A. monuste orseis prefered feeding on leaves of R. raphanistrum, than leaves of kale Brassica oleracea var. acephala.

Association of the soil bug Atarsocoris sp. (Hemiptera: Cydnidae) with the weed Senecio brasiliensis Less / Associação do percevejo Atarsocoris sp. (Hemiptera: Cydnidae) com a planta invasora maria-mole (Senecio brasiliensis Less)

The burrowing bugs of the family Cydnidae, among them the brown burrowing bug Atarsocoris sp., are insect pests occurring in various crops, resulting in substantial losses in areas with high populations. Atarsocoris sp. is also frequently associated with weeds. The insect was found in the roots of the plant S. brasiliensis Less in degraded pasture areas. Based on this observation, the hypothesis of a correlation between this weed plant and the insect was raised. A study was conducted in sandy soils (red latossol), in pasture areas with and without S. brasiliensis, with three treatments and 10 replicates. A positive correlation was found between the weed plant and the burrowing bug. Hence this plant is an alternative host under the conditions of the study (degraded pastures and sandy soil). The positive correlation detected allows suggesting the S. brasiliensis plant as a bio-indicator of the occurrence of this insect pests in these areas.

Os percevejos da família Cydnidae, entre eles Atarsocoris sp., são insetos-praga com ocorrência em várias culturas, acarretando perdas significativas em áreas com grande infestação do inseto; sendo também muito comuns associados a plantas daninhas. A ocorrência de Atarsocoris sp. foi observada em áreas de pastagens degradadas, nas raízes da planta maria-mole (Senecio brasiliensis Less). Mediante essa observação, foi levantada a hipótese da correlação entre a planta invasora e o inseto. O experimento foi realizado em solos de arenito (Latossolo Vermelho), em áreas de pastagem com a presença da maria-mole e sem a planta, totalizando três tratamentos e 10 repetições. Houve correlação positiva entre a planta invasora maria-mole e o percevejo (Atarsocoris sp.), sendo esta considerada uma hospedeira alternativa do inseto nas condições encontradas naquela área de estudo, ou seja, pastagens degradadas e solo arenoso. A correlação detectada permite sugerir a inclusão da maria-mole como bioindicadora do referido inseto nestas áreas.

Biologia e preferência da lagarta do girassol, Chlosyne lacinia saundersii (Lepidoptera: Nymphalidae) na planta daninha losna branca, Parthenium hysterophorus (Asteraceae) / Occurrence and biology of the sunflower caterpillar, Chlosyne lacinia saundersii (Doubleday) (Lepidoptera: Nymphalidae) on the weed plant, Parthenium hysterophorus (Asteraceae)

O objetivo deste trabalho foi estudar a biologia de Chlosyne lacinia saundersii Doubleday, sobre losna branca, Parthenium hysterophorus (Asteraceae), bem como avaliar sua preferência em relação ao girassol e à planta daninha. Os ovos foram coletados no campo sobre plantas de P. hysterophorus. A criação das lagartas foi realizada sob condições controladas de temperatura (25 ± 2ºC) e fotoperíodo (12 h L:12h E). A duração média da fase de ovo foi de sete dias; da fase larval de 18,9 dias, com 75 por cento de sobrevivência e da fase pupal de 6,1 dias, com 65 por cento de sobrevivência. C. lacinia saundersii preferiu alimentar-se de girassol, comparativamente à losna branca. A planta daninha P. hysterophorus constitui hospedeiro alternativo para a lagarta do girassol, permitindo que a mesma complete o ciclo biológico naquela planta.

This research aimed to study the biology of the sunflower caterpillar, Chlosyne lacinia saundersii (Doubleday), on Parthenium hysterophorus (Asteraceae) and to evaluate the preference between sunflower (Helianthus annuus) and the weed plant. The eggs were collected on plants of P. hysterophorus. Rearing procedures, from egg hatching to aduld emergence, were carried out under controlled enviromental conditions: 25 ± 2ºC, 70 ± 10 percent UR and 12:12h of photoperiod. The egg stage lasted seven days; the larval development took 18.9 days, with 75 percent survivorship; the pupal stage lasted 6.1 days, with 65 percent of survivorship. C. lacinia saundersii prefered to feed on sunflower comparatively to P. hysterophorus. The weed plant, P. hysterophorus, can be considered a host-plant for the sunflower caterpillar.

Performance of nymphs and adults of Piezodorus guildinii (Westwood) (Hemiptera: Pentatomidae) on soybean pods at different developmental stages

A study was conducted in the laboratory to test the suitability of soybean [Glycine max (L.) Merrill] pods at different phenological stages of development (R3-R8) on the performance of nymphs and adults of the small green stink bug Piezodorus guildinii (Westwood) (Hemiptera: Pentatomidae). Nymphs and adults showed better performance when fed on soybean pods during the pod-filling stage (R5-R6), compared to those fed on soybean pods at the remaining stages of development. When fed on soybean pods without seeds (R3-R4) no nymphs survived and no adults reproduced

O-Phosphonatomethylcholine, its analogues, alkyl esters, and their biological activity.

O-Phosphonatomethylcholine, an isopolar phosphocholine analogue with a phosphonomethyl ether group replacing a phosphomonoester residue, was prepared by reaction of diisopropyl 2-chloroethoxymethylphosphonate with dimethylamine followed by quaternization of the thus-obtained diisopropyl 2-dimethylaminoethoxymethylphosphonate with iodomethane; the ester groups in the quaternary intermediate were cleaved with bromotrimethylsilane. Replacement of dimethylamine in the reaction sequence by morpholine and/or pyrrolidine gave the N-methylmorpholinium or N-methylpyrrolidinium analogues of O-phosphonatomethylcholine. Reaction of O-phosphonomethylcholine monotetrabutylammonium salt with 1-bromoalkanes in acetonitrile afforded a series of the corresponding monoalkyl (C10-C16) esters. None of these compounds except for the hexadecyl ester exhibited any appreciable cytostatic activity against DU-145, H460, HT-29, or MES-SA cell lines in vitro (evaluated by 3H-Thd incorporation assay). The hexadecyl ester exhibited modest in vitro cytotoxic activity comparable to that of the anticancer drug miltefosine (hexadecyl O-phosphocholine). In vivo evaluation of hexadecyl O-phosphonomethylcholine [transplanted SD lymphoma in inbred SD/cub rats, 10 mg kg(-1) day(-1) intratumoral injection for 10 days] resulted in a 40% decrease in lymphoma mass.

Biodistribution of NX211, liposomal lurtotecan, in tumor-bearing mice.

Prolonging tumor exposure to topoisomerase I inhibitors has been correlated to enhance the efficacy of those agents. Lurtotecan, a water-soluble camptothecin analog, was formulated as a liposomal drug, NX211, to enhance the delivery of drug to tumors. Tumor-bearing mice were treated with either [14C]NX211 containing [14C]lurtotecan, [3H]NX211 containing [3H]phosphatidylcholine or [14C]lurtotecan, euthanized at selected times post-injection, and tissues, plasma, urine and feces were collected. These studies demonstrated that KB tumors of [14C]NX211-treated mice had approximately 70-fold greater concentrations of [14C]lurtotecan at 24 h, respectively, compared to concentrations of [14C]lurtotecan of the KB tumors of [14C]lurtotecan-treated mice. The area under curve (AUC) from 0 to 48 h of [14C]lurtotecan for the KB tumors of [14C]NX211-treated animals was over 17-fold greater than the AUC of [14C]lurtotecan for the tumors of [14C]lurtotecan-treated animals. Treatment with [3H]NX211 demonstrated that the lipid component continually accumulated over 24 h in the tissues. HPLC analysis of extracted material from tumors of [14C]NX211-treated mice showed that more than 95% of the radioactive material was intact [14C]lurtotecan. These findings are one of the keys justifying the development of a liposomal formulation of lurtotecan, which has the intent to increase tumor exposure and increase antitumor efficacy.

Antitumor efficacy, pharmacokinetics, and biodistribution of NX 211: a low-clearance liposomal formulation of lurtotecan.

Lurtotecan is a clinically active water-soluble camptothecin analogue that has been formulated into a low-clearance unilamellar liposome, NX 211. Comparative studies between free drug and NX 211 have been performed assessing pharmacokinetics in nude mice, tissue distribution in tumor-bearing mice, and antitumor efficacy in xenografts. Compared with lurtotecan, NX 211 demonstrated a significant increase in plasma residence time and a subsequent 1500-fold increase in the plasma area under the drug concentration curve. The volume of distribution was also greatly restricted, suggesting altered tissue distribution. Evaluation of tissues 24 h after administration of either [14C]NX 211 or [14C]lurtotecan to ES-2 tumor-bearing mice demonstrated a 40-fold increase in radiolabeled compound in the tumors of NX 211-treated mice compared with mice treated with lurtotecan. In single-dose efficacy studies, NX 211 produced a consistent 3-fold or greater increase in therapeutic index compared with lurtotecan in both the KB and ES-2 xenograft models. When compared at equitoxic levels in repeat-dose efficacy studies, NX 211 generated durable cures lasting >60 days and a 2-8-fold increase in log10 cell kill, compared with lurtotecan and topotecan, respectively. Together, these data demonstrate that NX 211 has significant therapeutic advantage over lurtotecan and that the improved antitumor activity is consistent with increased exposure and enhanced drug delivery to tumor sites.