Innovations in skin camouflaging techniques: Where are we scientifically?

OBJECTIVE: Cutaneous disorders can impact on the psycho-social well-being of children and adults alike, which has been reviewed elsewhere (Body Image 27, 2018 and 98). The present review sets out to evaluate progressions in skin masking and camouflaging techniques together with evaluating the efficacy of these. There does not appear to have been any recent reviews about innovations in skin camouflaging techniques. METHODS: Using the National Centre for Biotechnology Information PubMed database, a search was made for all studies published between 2000 and 2019 that met defined inclusion criteria. A total of seven relevant publications were identified. RESULTS: Of the seven studies identified, skin camouflaging improved quality of life in three studies and reduced anxiety, depression and social isolation in others. Of the camouflaging methods used, liquidized simulated second skin technology (Microskin™) appears to look particularly promising. This method of colour matching and a spray/stippling application uses a technology that binds to the epidermis of the skin helping to overcome previous concerns about the colour, coverage and application of camouflage and masking bases. Two studies showed that this innovative mode of camouflaging raised confidence, feelings of happiness and social experiences in children and adolescents with burn scarring. Very few studies reported drawbacks of camouflaging techniques, with limited colour matches and 'itching' appearing to be the main shortcomings. New technologies now appear to be addressing these. CONCLUSION: Results show that there is wide variation in the quality and modes of skin camouflaging. Of the methods used, simulated second skin technology appears to be an important and effective therapy for individuals with cutaneous skin disorders. Training schemes along with increased awareness of this technique must now be communicated to medical professionals who come into contact with children and adults who could benefit physically, psychologically and socially from this therapy.

OBJECTIF: Les troubles cutanés pouvant avoir un impact sur le bien-être psychosocial des enfants et des adultes a été examiné ailleurs. La présente revue vise à évaluer les progressions dans les techniques de masquage et de camouflage de la peau ainsi qu'à évaluer l'efficacité de ces techniques. Il ne semble pas y avoir eu de critiques récentes sur les innovations dans les techniques de camouflage de la peau. MÉTHODES: À l'aide de la base de données pubmed du Centre national d'information sur la biotechnologie, une recherche a été effectuée sur toutes les études publiées entre 2000 et 2019 qui satisfaisaient aux critères d'inclusion définis. Au total, sept publications pertinentes ont été identifiées. RÉSULTATS: Des sept études identifiées, le camouflage de peau a amélioré la qualité de vie dans trois études et a réduit l'inquiétude, la dépression et l'isolement social dans les autres. Parmi les méthodes de camouflage utilisées, la technologie simulée de la seconde peau (MicroskinTM) semble particulièrement prometteuse. Cette méthode d'appariement des couleurs et d'application par pulvérisation / par points utilise une technologie qui se lie à l'épiderme de la peau, ce qui permet de surmonter les problèmes de couleur, de couverture et d'application des bases de camouflage et de masquage. Deux études ont montré que ce mode de camouflage novateur augmentait la confiance, le sentiment de bonheur et les expériences sociales chez les enfants et les adolescents atteints de brûlures. Très peu d'études ont signalé les inconvénients des techniques de camouflage, les correspondances de couleurs limitées et les «démangeaisons¼ semblant être les principales lacunes. Les nouvelles technologies semblent maintenant répondre à ces problèmes. CONCLUSION: Les résultats montrent qu'il existe une grande variation dans la qualité et les modes de camouflage de la peau. Parmi les méthodes utilisées, la technologie de la seconde peau simulée semble être un traitement important et efficace pour les personnes souffrant de troubles cutanés. Les programmes de formation associés à une sensibilisation accrue à cette technique doivent maintenant être communiqués aux professionnels de la santé qui entrent en contact avec des enfants et des adultes susceptibles de tirer un bénéfice physique, psychologique et social de cette thérapie.

Omega-3 fatty acids - A review of existing and innovative delivery methods.

Omega-3 fatty acids are generally under-consumed in Western diets; a factor that may largely be attributed to low intake of oily fish. Although supplementation strategies offer one approach in terms of improving blood fatty acid levels, rates of compliance are generally low due to difficulties in swallowing capsules, or unfavorable aftertastes. Consequently, new approaches, including food-based strategies, may be an alternative approach to improving omega-3 status and the health of public sectors. This paper sets out to discuss and review how the use of novel food vehicle and delivery advancements may be used to improve omega-3 status, which may have wider benefits for public health and well-being.

Role of fatty acids and micronutrients in healthy ageing: a systematic review of randomised controlled trials set in the context of European dietary surveys of older adults.

BACKGROUND: Ageing is a multifaceted and inevitable process involving a decline in health and well-being that could be ameliorated by dietary modification. We review and discuss the evidence for nutritional interventions that may support healthy ageing. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to identify randomised controlled trials investigating the role(s) of fatty acids and micronutrients in relation to markers of healthy ageing. RESULTS: European dietary surveys suggest that diets in elderly people are generally high in saturated fat, whereas intakes of vitamin D, magnesium, potassium, zinc and copper are below recommended levels. Thirty-four studies meeting the criteria were found, with 12 of these investigating the role of fatty acids and 22 considering intakes of micronutrients in relation to healthy ageing. Overall, these studies suggested that certain nutrients were consistent with healthy ageing; for example, omega-3 fatty acids were helpful for cognitive health, whereas combinations of calcium, vitamin D and K were linked with better bone health. CONCLUSIONS: Vitamin, mineral and fatty acid intakes are in need of improvement to help elderly populations achieve optimal diet quality and support healthy ageing. This could involve the judicious use of supplements alongside dietary advice. Additional research is needed to determine optimal nutrient doses, combinations and forms in relation to desired health outcomes.

Could capsaicinoids help to support weight management? A systematic review and meta-analysis of energy intake data.

OBJECTIVE: Capsaicinoids are a group of chemicals naturally occurring in chilli peppers with bioactive properties that may help to support weight management. The aim of the present study was to conduct a meta-analysis investigating the potential effects of capsaicinoids on energy intake, to clarify previous observations and form evidence-based conclusions about possible weight management roles. METHODS: Medical databases (Medline, Web of Knowledge and Scopus) were systematically searched for papers. Search terms were: 'capsaicin(*)' or 'red pepper' or 'chilli(*)' or 'chili(*)' with 'satiety' or 'energy intake'. Of the seventy-four clinical trials identified, 10 were included, 8 of which provided results suitable to be combined in analysis (191 participants). From the studies, 19 effect sizes were extracted and analysed using MIX meta-analysis software. RESULTS: Data analysis showed that capsaicinoid ingestion prior to a meal reduced ad libitum energy intake by 309.9kJ (74.0kcal) p<0.001 during the meal. Results, however, should be viewed with some caution as heterogeneity was high (I(2)=75.7%). Study findings suggest a minimum dose of 2mg of capsaicinoids is needed to contribute to reductions in ad libitum energy intake, which appears to be attributed to an altered preference for carbohydrate-rich foods over foods with a higher fat content. CONCLUSIONS: Meta-anlysis findings suggest that daily consumption of capsaicinoids may contribute to weight management through reductions in energy intake. Subsequently, there may be potential for capsaicinoids to be used as long-term, natural weight-loss aids. Further long-term randomised trials are now needed to investigate these effects.

A review of the nutritional composition, organoleptic characteristics and biological effects of the high oleic peanut.

A growing body of literature has been published on the health benefits of peanuts, but the potential biological effects of high-oleic (HO) peanuts, along with their organoleptic characteristics have not been reviewed to date. In this paper, examination of evidence showed that HO peanuts provide a spectrum of nutrients and have improved sensory properties and technological advances, such as enhanced shelf life, beyond that of conventional peanuts. This may be attributed to their oleic to linoleic ratio (OL ratio) which is substantially (around 10 times) higher than normal peanuts. In terms of their biological effects, HO peanuts appear to be no more allergenic, and could even be less allergenic than conventional peanuts. There is also emerging evidence that HO peanuts may improve lipid profile and markers of glycemic control. Further randomized controlled human trials are now needed to build on animal and in vitro studies.

A study to establish whether food-based approaches can improve serum iron levels in child-bearing aged women.

BACKGROUND: Iron-deficiency anaemia is particularly prevalent in pregnancy. The present study aimed to determine whether functional bread containing teff flour (i.e. naturally rich in iron) could be an alternative way of improving iron status. However, before testing whether its consumption can improve pregnancy iron status, the bio-availability of iron was determined in a sample of nonpregnant women. METHODS: Fifty-eight women (20-50 years) were recruited from the University. Blood samples were taken at baseline to assess iron status and participants were screened to account for other factors affecting iron status. Twenty-four participants (haemoglobin 9.5-14.0g dL(-1) ) were recruited to take part in the intervention and allocated to five groups: (i) control bread (CB); (ii) teff bread (TB); (iii) TB+level 1 phytase (TB+P1); (iv) TB+level 2 phytase (TB+P2); or (v) a supplement containing 10 mg of ferrous sulphate. Venous blood samples were taken before the intervention and after 180-210min, aiming to determine changes in serum iron. RESULTS: Consuming three or four slices of TB provided statistically significantly more iron (7.6mg) than CB (5.1mg) (P<0.001). Because participants were fasted, serum iron levels declined in all bread groups (average -1.5µm), although the smallest reduction was observed in the TB+P2 group (-0.3 µm). The area-under-the-curve from baseline to 210min was lower in the TB+P2 (-78.8µmol min L(-1) ) group compared to the other bread interventions, indicating higher levels of iron absorption in this group. CONCLUSIONS: The results obtained in the present study show that TB consumption may help to maintain serum iron levels, especially when phytase is added. The findings from the study also demonstrate there may be potential to further improve the bio-availability of iron from non-haem food sources.

Can an iron-rich staple food help women to achieve dietary targets in pregnancy?

Habitual iron intakes during pregnancy are typically lower than dietary guidelines, a risk for iron deficiency. The aim of this study was to determine whether regular consumption of bread naturally rich in iron could help women to achieve dietary targets. Thirty-three primiparous mothers were randomized to eat 3-4 slices of iron-rich or control bread daily for 6 weeks. Two 24-h-prompted (multiple-pass) dietary recalls were completed, and validated algorithms were used to determine the amount of 'available iron' from the diet. Regular consumption of iron-rich bread helped pregnant women to achieve UK dietary recommendations; the quantity of bread consumed by the participants contributed 27% versus 9% UK Reference Nutrient Intake (RNI) (14.8 mg/d) in the intervention versus the control group. Levels of total 'available iron' were similar in both groups and correlated positively with total dietary iron (r = 0.78, P = 0.0001), vitamin C (r = 0.43, P = 0.017) and non-haem iron (r = 0.77, P = 0.0001). Findings from this study show that iron-rich staple foods can help women reach dietary targets for iron. This is an area of great potential that could be of particular benefit to low-income/ethnically diverse population groups who have some of the lowest iron intakes. Further research using fortified staple foods containing higher levels of iron is now warranted to establish physiological benefits.

A randomized trial investigating an iron-rich bread as a prophylaxis against iron deficiency in pregnancy.

The iron-rich bread (2.2 mg iron per 50 g slice) used in the study was developed using Eragrostis tef flour, naturally rich in iron. Iron deficiency is prevalent in pregnancy and compliance with supplements can be low. In this double-blind, randomized trial 34 Caucasian, primiparous antenatal patients were randomized to receive intervention bread or a placebo for 6 weeks. Women consumed on an average of 2.3 slices per day, providing a total of 5.0 mg iron. Using World Health Organisation (2001) haemoglobin cut-offs, 12% of participants eating the iron-rich bread were iron deficient by the end of the study compared with 27% in the control group. For other markers of iron status, these were improved in the placebo versus the treatment group. For example, a significant decline in serum iron and transferrin saturation was not observed in this group. Findings demonstrate that other modes of delivery, i.e. food fortification, may be needed to generate 'physiological effects', or further measures are taken to improve intervention compliance.

Habitual micronutrient intake during and after pregnancy in Caucasian Londoners.

Micronutrient status is of fundamental importance both upon conception and throughout pregnancy. There is an abundance of literature investigating nutrient intakes during individual trimesters of pregnancy but few studies have investigated baseline intakes of nutrients throughout gestation as a continuum. The current investigation set out to measure habitual micronutrient intakes at weeks 13, 25, 35 of pregnancy and 6 weeks postpartum using a prospective background information questionnaire, 4-7-day weighed food diary and postnatal questionnaire. Seventy-two primiparous, Caucasian Londoners were recruited at the study start with 42 completing the first, second, third trimester and postpartum study stages respectively. Study findings indicated that sodium intakes were significantly higher than UK guidelines throughout and after pregnancy (P < 0.001). Intakes of folate, iron, vitamin D, potassium, iodine and selenium were lower than UK recommendations during and after pregnancy, but to varying levels of statistical significance (P < 0.05). Only 23-38% of women met UK recommendations for folate (300 microg day(-1)) through dietary sources. Similarly, only a small percentage of women met dietary guidelines for iron (19-28%). The findings from the current study indicate that public health interventions may be required to help expectant mothers achieve an optimal diet, particularly after birth when dietary recommendations increase for some micronutrients.

Habitual caffeine intake in women of childbearing age.

BACKGROUND: For women, delayed conception and recurrent pregnant loss are just a few of the health implications associated with a caffeine-rich diet (Mol. Hum. Reprod., 11, 357). At present there is a deficit of prospective research measuring current habitual intakes of caffeine in UK women. The purpose of the current study was to collect up-to-date baseline data to assess caffeine intake and knowledge in a group of women (aged 16-45 years). METHODS: Seventy Caucasian subjects (mean age 30.4 +/- 8.7 years) were recruited from business offices within the Manchester area. Each participant completed a 3-day food diary and lifestyle questionnaire. RESULTS: The mean intake of caffeine was 173.95 mg day(-1) (+/-128.39 mg day(-1)). Eighteen per cent of subjects exceeded caffeine guidelines and consumed 300 mg caffeine or more each day. Subjects consuming over 300 mg day(-1) were more likely to be older (P = 0.016) and smokers (P = 0.000). Individuals given previous advice about caffeine and health, had lower intakes (P = 0.002). CONCLUSIONS: Many women are unaware of health perturbations associated with caffeine consumption. A diet abundant in caffeine may result in delayed conception, infertility and increased risk of osteoporosis, cardiovascular disease and cancer later in life. Such information needs to be conveyed to the public sector. Future research is also required to devise specific caffeine guidelines, particularly safe upper limits.

Do Omega-3/6 Fatty Acids Have a Therapeutic Role in Children and Young People with ADHD?

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a debilitating behavioural disorder affecting daily ability to function, learn, and interact with peers. This publication assesses the role of omega-3/6 fatty acids in the treatment and management of ADHD. METHODS: A systematic review of 16 randomised controlled trials was undertaken. Trials included a total of 1,514 children and young people with ADHD who were allocated to take an omega-3/6 intervention, or a placebo. RESULTS: Of the studies identified, 13 reported favourable benefits on ADHD symptoms including improvements in hyperactivity, impulsivity, attention, visual learning, word reading, and working/short-term memory. Four studies used supplements containing a 9 : 3 : 1 ratio of eicosapentaenoic acid : docosahexaenoic acid : gamma linolenic acid which appeared effective at improving erythrocyte levels. Supplementation with this ratio of fatty acids also showed promise as an adjunctive therapy to traditional medications, lowering the dose and improving the compliance with medications such as methylphenidate. CONCLUSION: ADHD is a frequent and debilitating childhood condition. Given disparaging feelings towards psychostimulant medications, omega-3/6 fatty acids offer great promise as a suitable adjunctive therapy for ADHD.

Heparin-steroid conjugates: new angiogenesis inhibitors with antitumor activity in mice.

Inhibitors of angiogenesis hold potential in the treatment of cancer and other diseases where the disease is caused or maintained by the inappropriate growth of blood vessels. In the present study, a novel inhibitor of angiogenesis was synthesized by covalently linking a nonanticoagulating derivative of heparin, heparin adipic hydrazide (HAH), by an acid-labile bond to the antiangiogenic steroid, cortisol. The rationale was that the heparin derivative, which binds to sulfated polyanion receptors on endothelial cells, should concentrate the steroid on the surface of vascular endothelial cells. Endocytosis of the conjugate and decomposition of the acid-labile linkage inside lysosomes and other acidic intracellular compartments should then lead to release of the cortisol and expression of its antiproliferative activity. Analysis of the stability of HAH-cortisol showed that it was stable at pH 7.4 and broke down rapidly (t1/2 15 min) at pH 4.8 at 37 degrees C. Treatment of murine pulmonary capillary endothelial cells with HAH-cortisol at 10(-5) M (with respect to cortisol) suppressed their DNA synthesis by 50% and inhibited their migration into wounded areas of confluent monolayers. HAH-cortisol at 10(-4) M (with respect to cortisol) did not suppress the DNA synthesis of Lewis lung carcinoma cells. Daily i.p. injections of HAH-cortisol into mice bearing s.c. sponge implants retarded vascularization of the sponge, and injections directly into the sponge abolished vascularization for as long as the injections were continued. Daily i.v. injections of HAH-cortisol at doses causing no apparent toxicity retarded the growth of solid s.c. Lewis lung carcinomas in mice by up to 65%. In all of these assays, equivalent treatments with a mixture of the HAH plus cortisol was significantly less effective. The antiproliferative effect of HAH-cortisol on endothelial cells appeared independent of the glucocorticoid activity of the steroid since HAH conjugated to 5 beta-pregnane-3 alpha,17 alpha,21-triol-20-one, a steroid lacking glucocorticoid or mineralocorticoid activity, was even more effective at inhibiting DNA synthesis by murine pulmonary capillary endothelial cells than was HAH-cortisol. In conclusion, HAH-cortisol represents the prototype of a new class of angiogenesis inhibitors for the treatment of cancer and other angiogenic diseases.

Heparin-steroid conjugates lacking glucocorticoid or mineralocorticoid activities inhibit the proliferation of vascular endothelial cells.

A new class of angiogenesis inhibitors consist of a non-anticoagulating derivative of heparin, which binds to vascular endothelial cells, coupled to a steriod (e.g., cortisol) which suppresses endothelial cell division. We linked heparin to a further 10 steroids in an effort to identify ones which would yield more effective or safer angiogenesis inhibitors. Steroids having a C3 ketone group were linked by reaction with a hydrazide derivative of heparin. Steroids having a C20 ketone group and lacking a C3 ketone could not be prepared by this method, necessitating the development of alternative methods. The most efficient was to convert the steroid into a derivative having a hydrazone group at C20 and then link the steroid hydrazone to heparin. Conjugates prepared from steroids having C3 ketones were at most 6-fold more inhibitory than the free steroids to endothelial cells in tissue culture. In contrast, steroids having a C20 ketone but lacking a C3 ketone (tetrahydrocortisone, tetrahydrocortisol and tetrahydro S) became highly inhibitory to endothelial cells only after conjugation to heparin. They inhibited [3H]thymidine incorporation by 50% at a steroid concentration of 18-30 microM and by 95% at 300 microM. Since tetrahydrocortisone, tetrahydrocortisol and tetrahydro S lack glucocorticoid and mineralocorticoid activity, they may prove safer alternatives to cortisol for prolonged administration, as is likely to be necessary with anti-angiogenic therapies.

Up-regulation of endoglin on vascular endothelial cells in human solid tumors: implications for diagnosis and therapy.

We have characterized a murine IgM monoclonal antibody, TEC-11, that recognizes endoglin and may be suitable for targeting cytotoxic agents to human tumor vasculature. TEC-11 strongly stains endothelial cells in a broad range of solid human tumors while staining endothelial cells in the majority of normal, healthy adult tissues relatively weakly. Human umbilical vein endothelial cells (HUVECs) in sections of the umbilical vein react weakly with TEC-11, whereas proliferating HUVECs in tissue culture react strongly and uniformly. HUVEC cultures grown to confluence and then rested contain two subpopulations having high and low levels of endoglin expression. Flow cytometry revealed that a significant proportion of cells with high endoglin expression are cycling, having markedly increased levels of cellular protein, RNA, and DNA by comparison to low endoglin-expressing cells, which appear to be noncycling. Taken together, the increased binding of TEC-11 to tumor vasculature and to dividing as opposed to noncycling HUVECs in vitro suggests that endoglin is an endothelial cell proliferation-associated marker. An immunotoxin [TEC-11.deglycosylated ricin A chain (dgA)] composed of TEC-11 and dgA was 3000-fold more potent at inhibiting protein synthesis in proliferating HUVEC cultures than in confluent cultures. The confluent cells were no more sensitive to TEC-11.dgA than they were to an isotype-matched immunotoxin of irrelevant specificity. These findings suggest that TEC-11.dgA might have therapeutic value in the treatment of solid tumors in humans by selectively killing dividing endothelial cells which are prevalent in such tumors.

Neutropenia occurring after starting gabapentin for neuropathic pain.

We report a case of neutropenia occurring in a patient receiving gabapentin for neuropathic pain. Five weeks after treatment started, the patient was admitted to hospital with neutropenic sepsis. Gabapentin is widely used, and neutropenia is a rare adverse effect. This case highlights a serious and potential life-threatening complication.

[Electrophoretic analysis of buckwheat flour compared with regular wheat flour]. / Análise eletroforética da farinha de trigo sarraceno em comparação com a farinha de trigo suave.

The composition of the alcohol soluble proteins (prolamins) obtained from buckwheat meal and common wheat flour by two procedures were analysed by electrophoresis at pH 3.1 and, after dissociation, in the presence of sodium dodecyl sulphate at pH 8. The profiles obtained from the prolamin fraction of buckwheat were very different, qualitatively and quantitatively, from those of the prolamin of common wheat. It is probable therefore that the adverse effects associated with the presence of wheat gliadin in diets of patients with celiac disease would be reduced and possibly avoided if wheat flour were replaced by flour from buckwheat.

Prepregnancy body mass index and dietary intake in the first trimester of pregnancy.

OBJECTIVES: Adequate maternal nutrition is of paramount importance in pregnancy, particularly in the first trimester when fetal development is crucial. It has been reported that heavier women are most likely to fear weight gain associated with pregnancy. Few studies have, however, investigated associations between prepregnancy body mass index (BMI) and nutrient intakes in the first trimester of gestation using detailed, prospective methodologies. The aim of this study was to investigate possible associations between prepregnancy BMI and nutrient intakes in the first trimester of gestation. DESIGN: Seventy-two Caucasian, primiparous nonsmokers of mean age 33.1 years (SD 4.6) were recruited from three London teaching hospitals and they completed a background information questionnaire and a 4- to 7-day weighed inventory food diary during the first trimester of pregnancy. Prepregnancy anthropometric data were extracted from General Practitioner records. RESULTS: Prepregnancy BMI was inversely associated with dietary energy (P = 0.04), Southgate and Englyst fibre (P < 0.01), and iron and folate (P < 0.01). After excluding under-reporters [individual energy intake:basal metabolic rate (estimated) ratio < 1.2], prepregnancy BMI was inversely associated with folate intake (P =0.04). Dietary intakes of Englyst fibre (P = 0.03) were statistically significantly lower than average dietary recommendations in this group. CONCLUSIONS: This study identified that women with a high prepregnancy BMI are more likely to under-report nutrient intakes. The finding that folate intake was significantly lower in heavier women accurately reporting dietary intake is of particular concern.

Monoclonal antibodies recognising the cluster 2 antigen associated with human small cell lung cancer mediate the toxic effects of ricin A chain in an indirect assay of immunotoxin cytotoxicity.

Monoclonal antibodies (Mabs) submitted to the Second International Workshop on Small Cell Lung Cancer Antigens were screened for their ability to mediate the toxic effects of ricin A chain against the NCI-H69 cell line in an indirect assay of immunotoxin cytotoxicity. Cluster 1 Mabs, recognising the neural cell adhesion molecule, mediated little or no cytotoxic effect in combination with screening agent, ricin A chain linked to an antibody Fab' fragment recognising either mouse or rat Mabs. In contrast, cluster 2 Mabs, recognising an epithelial tumour-associated antigen, generally mediated potent cytotoxic effects with the screening agent, inhibiting the incorporation of 3H-leucine by NCI-H69 cells by between 90% and 99%. Measurements of Mab binding to the NCI-H69 cell line by indirect immunofluorescence and flow cytometry indicated that the cluster 2 Mabs generally bound in higher amounts than the cluster 1 Mabs suggesting that the cluster 1 Mabs were ineffective in the screen because they did not bind to the cells in sufficient amounts. However, Mabs recognising antigens other than cluster 1 bound to NCI-H69 cells in amounts similar to those of the cluster 2 Mabs yet did not mediate potent cytotoxic effects in the indirect assay suggesting that the cluster 2 antigen may be internalised in a fashion favouring the delivery of ricin A chain to the cytosol.

Immunotoxins to human small-cell lung cancer.

Ricin A chain ITs directed against a variety of the common cell-surface antigens associated with SCLC exerted selective toxic effects on SCLC cell lines. The potency of the cytotoxic effects matched or exceeded that previously reported for ricin A chain ITs directed against identical or similar antigens on other types of carcinoma, suggesting that SCLC may be uniquely sensitive to this type of IT.

An anti-mucin immunotoxin BrE-3-ricin A-chain is potently and selectively toxic to human small-cell lung cancer.

Monoclonal antibodies (MAbs) known to recognize epithelial mucin or defined carbohydrate structures present on mucin molecules were screened for their ability to form cytotoxic agents with ricin A-chain active against human small-cell lung cancer (SCLC) in an indirect assay of immunotoxin cytotoxicity. Anti-X hapten and anti-Y hapten antibodies binding to a high proportion of SCLC cells mediated only weak to moderate effects on 3H-leucine incorporation in combination with the screening agent, sheep anti-mouse IgG F'ab-ricin A-chain. In contrast, the mouse MAb BrE-3, recognizing the polypeptide core of the MUCI mucin gene product, exerted potent and selective cytotoxic effects in the assay. An immunotoxin made by the direct attachment of ricin A-chain to BrE-3 was selectively toxic to SCLC cell lines in tissue culture. The cytotoxic activity of BrE-3-ricin A-chain was enhanced 100-fold in the presence of monensin but not by lysosomotropic amines or calcium antagonists. Our findings suggest that anti-mucin immunotoxins may have a therapeutic role to play in the treatment of SCLC.