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To cut the high mortality rate of malignant disease such as pancreatic cancer, development of newly diagnostic probes for early stage detection of tumor lesions is required. Multimodal imaging nanoprobes allowing targeted and real time functional/anatomical imaging of tumors meet the demands. For this purpose, a MRI/optical dual-modality probe based on biodegradable magnetic iron oxide nanoworms has been developed. The cross-linked surface of nanoworms were anchored to fluorescent dyes and to FITC.PTR86; a novel synthetic peptide with high affinity towards somatostatin receptors. Combination of various in vitro techniques including Prussian blue staining, fluorescent microscopy and fluorescence activated cell sorting (FACS) have been performed to explore the interaction of developed nanoprobe with pancreatic tumor cell lines. Together with in vivo studies in a xenograft mouse model of human pancreatic adenocarcinoma and ex vivo investigations, the results show the efficient imaging and targeting of pancreatic tumors by our newly developed nanosystem using both MRI and optical imaging modalities.

Functionalized nanoparticles decorated with functional biological entities serve as preferred vehicles for numerous theranostic applications. Here we offer an alternative strategy in which the targeting moieties also act as building blocks for the formation of functional nano-assemblies. Diphenylalanine, a small, highly potent self-assembling module, was incorporated with a somatostatin analogue, a modified hormone which preferentially binds to cancer cells. The co-assembly of the engineered hormone together with the structurally diverse diphenylalanine derivative allowed the formation of bioactive homogenous spherical nanostructures. Significant internalization capacity of the loaded co-assembled nanospheres into cancer cells in vitro, as well as selective in vivo accumulation in tumors, were demonstrated. These findings present a new method for the molecular engineering of bioactive peptide molecules by minor modifications with a remarkably potent association motif.

Q-switched neodymium:YAG (Nd:YAG) lasers are reported to be gold standard for laser tattoo removal. In particular, the Q-switched Nd:YAG laser at 1064 nm is widely recognized for the removal of blue/black amateur tattoos. However, treatment modalities in Fitzpatrick Type VI skin carry a greater risk of complications including alterations in pigmentation compared to fairer skin (Fitzpatrick Type I-IV skin). Therefore, the aim of this case series was to describe with the use of the Q-Switched Nd:YAG laser, the removal of carbon-based amateur tattoos on patients with Fitzpatrick Type VI skin as an effective and safe method.Twenty- five patients with Fitzpatrick type VI skin, from Ethiopian origins, with facial tribal tattoos, were treated with the Q- Switched Nd:YAG laser at 1064 nm. Digital images were taken upon every treatment and the clearance rates of the tattoo was evalu- ated by imaging software.We observed an average tattoo clearance rate of 95% among the 45 facial tattoos in 25 patients presented in the case series with minimal pigmentary and textual changes evident.These positive aesthetic results have a signi cant psychosocial impact on the lives of those with Fitzpatrick Type VI skin, in particular the Ethiopian Jewish population.emJ Drugs Dermatol. 2016;15(11):1448-1452./em.

The development of tools for the early diagnosis of pancreatic adenocarcinoma is an urgent need in order to increase treatment success rate and reduce patient mortality. Here, we present a modular nanosystem platform integrating soft nanoparticles with a targeting peptide and an active imaging agent for diagnostics. Biocompatible single-chain polymer nanoparticles (SCPNs) based on poly(methacrylic acid) were prepared and functionalized with the somatostatin analogue PTR86 as the targeting moiety, since somatostatin receptors are overexpressed in pancreatic cancer. The gamma emitter 67Ga was incorporated by chelation and allowed in vivo investigation of the pharmacokinetic properties of the nanoparticles using single photon emission computerized tomography (SPECT). The resulting engineered nanosystem was tested in a xenograph mouse model of human pancreatic adenocarcinoma. Imaging results demonstrate that accumulation of targeted SCPNs in the tumor is higher than that observed for nontargeted nanoparticles due to improved retention in this tissue. ¸ 2016 American Chemical Society.

The treatment of tinea capitis using radiotherapy was introduced at the beginning of the twentieth century. In Israel, between 1949 and 1960, approximately 17,000 children underwent radiotherapy treatments for tinea capitis (actual numbers are probably higher due to irradiation in countries of origin as a prerequisite for immigration). Skin cancer presents a major problem for patients who underwent irradiation for the treatment of tinea capitis [aggressive biological behavior, multiple basal cell carcinomas (BCCs), up to 40 lesions in a single patient, with no predisposing condition such as Gorlin's or Bazex's syndromes]. There are ample data in the literature concerning the molecular changes in ultraviolet (UV) radiation-induced BCCs. However, similar data regarding ionizing radiation-induced BCCs are scarce. One work found higher rates of p53 and PTCH (both are tumor suppressor genes whose alterations are associated with BCC formation and frequency, but not biological behavior) abnormalities in post ionizing radiation BCCs. The absence of documented differences in gene expression that would account for a different biological behavior of radiotherapy-related BCCs, coupled with the aggressive and recurrent nature of these lesions, has propelled us to examine these differences by comparing gene expression in BCCs of the scalps of patients who were previously irradiated for tinea capitis in their childhood and of the scalps of patients who were not.Tissue samples of excised scalp BCCs from seven previously irradiated patients (five male, two female) and seven not previously irradiated patients (six male, one female) were frozen upon excision and genetically analyzed using DNA microarray chips.No correlation was found between previous ionizing irradiation and gene expression.The negative results of this study, coupled with the observation of aggressive biological behavior of BCCs in previously irradiated patients merit further attention. Other explanations for the aggressive biological behavior of radiotherapy-induced BCCs come to mind. One such explanation could be that the difference between the groups lies not in the tumor itself, but in the host, who is more susceptible to the local destruction caused by the tumor due to changes in the surrounding tissue (e.g., impaired blood supply due to radiation, structural damage in seemingly healthy skin). This hypothesis will be the focus of further research.This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The treatment of burn victims constitutes a considerable challenge both to the clinician in regard to mundane treatment and to health systems in regard to structural organization. The state of Israel is in dire need of competent burn care capabilities for political, geographical, and demographic reasons. Israel currently has five designated burn units but no burn center. A review of the recent literature suggests that larger burn centers can convey lower mortality rates and better functional outcomes for severe burn patients in comparison to smaller burn units. The objective of this study is to assess Israel's burn care alignment needs and capabilities based on Israel's burn patient and burn unit data. In addition, the authors aim to compare the burn care alignment capabilities with those of the country's European and American counterparts. Data of all the burn patients hospitalized in Israel's level 1 trauma centers' burn units between the years 1998 and 2005 according to the Israeli Trauma Registry were analyzed. Simultaneously, data regarding the setup and arrangement of each burn unit were obtained from each burn unit director via phone. Between the years 1998 and 2005, 974 adult patients with burns of the second degree or higher spanning 20% TBSA and more were hospitalized in the five hospitals that operate a functional specialized burn unit. The average hospitalization period was 32.4 days while the mortality rate was 21.1%. Currently, Israel's five burn units report possessing 27 burn beds and 14 burn intensive care unit beds. Due to the continuous risk for terror attacks and military campaigns and due to Israel's inability to refer excess burn patients to neighboring countries, Israel desperately needs efficient burn care capabilities. Israel currently trails both the United States and Europe in regard to burn beds and burn centers per population. The annual quantity and severity of burn patients in Israel largely exceeds the amount needed to justify an establishment of a burn center by the current American Burn Association guidelines, while the literature provides vast amount of evidence proving burn centers' efficacy in improving outcome, shortening hospitalization periods, and reducing costs. Taking all these elements into consideration, it might be prudent to establish a national burn center in Israel to promote burn care standards and disaster planning up to international standards.

The newly reconstructed nipple is extremely sensitive to mechanical pressure and shearing forces, which can cause flap necrosis and sloughing of the skin, eventually promoting infection. Current available dressing solutions are cumbersome, inefficient, displeasing, or otherwise not readily obtainable.In this study, 10 patients with newly reconstructed nipples were instructed to use breastfeeding nipple shields as the sole means of nipple dressing after the reconstruction procedure.No complications were observed overall. Patients reported full adherence to the postoperative dressing regimen as well as ease of use, availability, low costs, and pleasing aesthetic appearance under garments.Silicone breastfeeding nipple shields offer an efficient, affable, cheap, widely available, and aesthetically pleasing form of postoperative dressing for reconstructed nipples. Their use may enhance patient compliance with the dressing regimen and lower the postoperative complication rate.

It was previously shown that CEACAM1 on melanoma cells strongly predicts poor outcome. Here, we show a statistically significant increase of serum CEACAM1 in 64 active melanoma patients, as compared to 48 patients with no evidence of disease and 37 healthy donors. Among active patients, higher serum CEACAM1 correlated with LDH values and with decreased survival. Multivariate analysis with neutralization of LDH showed that increased serum CEACAM1 carries a hazard ratio of 2.40. In vitro, soluble CEACAM1 was derived from CEACAM1(+), but neither from CEACAM1(-) melanoma cells nor from CEACAM1(+) lymphocytes, and directly correlated with the number of CEACAM1(+) melanoma cells. Production of soluble CEACAM1 depended on intact de novo protein synthesis and secretion machineries, but not on metalloproteinase function. An unusually high percentage of CEACAM1(+) circulating NK and T lymphocytes was demonstrated in melanoma patients. CEACAM1 inhibited killing activity in functional assays. CEACAM1 expression could not be induced on lymphocytes by serum from patients with high CEACAM1 expression. Further, expression of other NK receptors was impaired, which collectively indicate on a general abnormality. In conclusion, the systemic dysregulation of CEACAM1 in melanoma patients further denotes the role of CEACAM1 in melanoma and may provide a basis for new tumor monitoring and prognostic platforms.

SummaryAn efficient immune response against tumours depends on a well-orches-trated function of integrated components, but is finally exerted by effectortumour-infiltrating lymphocytes (TIL). We have previously reported thathomophilic CEACAM1 interactions inhibit the specific killing and inter-feron-c (IFN-c) release activities of natural killer cells and TIL. In thisstudy a model for the investigation of melanoma cells surviving long co-incubation with antigen-specific TIL is reported. It is demonstrated thatthe surviving melanoma cells increase their surface CEACAM1 expression,which in turn confers enhanced resistance against fresh TIL. Furthermore,it is shown that this is an active process, driven by specific immune recog-nition and is at least partially mediated by lymphocyte-derived IFN-c.Similar results were observed with antigen-restricted TIL, either auto-logous or allogeneic, as well as with natural killer cells. The enhancedCEACAM1 expression depends, however, on the presence of IFN-c andsharply drops within 48 hr. This may be a mechanism that allows tumourcells to transiently develop a more resistant phenotype upon recognitionby specific lymphocytes. Therefore, this work substantiates the melanoma-promoting role of CEACAM1 and marks it as an attractive target fornovel immunotherapeutic interventions.Keywords: cell surface molecules; T cells; tolerance/suppression/anergy;tumour immunity

Colorectal carcinoma is one of the more prevalent, highly malignant human tumors, occurring in about 7% of the population. However, if diagnosed and treated in its early stages, colon cancer is curable. In our study, we used a mouse xenograft model to investigate the capability of a fluorescent conjugate of a novel synthetic somatostatin (SST) analog to improve detection of human colorectal tumors that are characterized by over-expressed SST receptors. Human HT-29 colon carcinomas were induced in nude mice. After administration of the fluorescent SST conjugate, in vivo low- and high-magnification fluorescence microscopy, as well as high-resolution spectrally resolved imaging were performed, and the time-dependent biodistribution was determined quantitatively (using fiber-optic spectroscopy). Administration of the conjugate (at concentrations of 6 mg/kg body weight) enabled targeting small (1–5 mm diameter) tumors with high sensitivity and selectivity. Toxicity studies at dosages up to 1,000 mg/kg body weight did not reveal any drug related abnormalities. In conclusion, the SST conjugate significantly enhanced the detection of HT-29 colon tumors by fluorescence imaging because of a 5- to 8-fold increase in the contrast between malignant and normal tissues. © 2008 Wiley-Liss, Inc.

Suction-assisted lipoplasty (SAL; liposuction) is an established aesthetic procedure in plastic surgery. The main parameters differentiating one method of lipoplasty from another are safety, consistency of results, and other more technical parameters. Due to the recent popularity of lipotransfer, the quality of extracted fat has become a relevant parameter. We compare the viability of extracted adipocytes after dry SAL, hyper-tumescent PAL (power-assisted lipoplasty), and water-assisted lipoplasty (WAL). We used fluorescent microscopy to differentiate viable from necrotic/apoptotic cells after liposuction using each of the mentioned methods. The ratio of living cells between the three methods was significantly different with dry liposuction yielding inferior ratios (p = 0.011). When omitting extreme results, we found that the body-jet technique (WAL) yielded higher ratios of living cells than the hyper-tumescent technique (p

Bio-Alcamid (Polymekon, Milan, Italy) is a relatively new, nonabsorbable hydrogel polymer that is used as a permanent filler for cosmetic and reconstructive purposes. The polymer, derived from acrylic acid, has a reticulated structure. It is an alkylic resin containing 96% pyrogen-free water and 4% alkylimide-amide groups. Owing to these chemical properties, Bio-Alcamid is stable and resistant to hydrolysis. It has been suggested that the filler should be considered totally biocompatible as far as the effects on cell proliferation and cell functions are concerned, thus rendering it suitable for long-term reconstruction of tissue damage even when large amounts of the polymer are used.

An ingrowing toenail is an excessive lateral nail growth into the nail fold. It acts as a foreign body and exerts a local pressure sore-like effect, which may result in inflammation and granulation. Several treatment modalities exist, including chemical ablation and different surgical procedures. Here we describe and compare a simple and effective method of partial matricectomy using the CO2 laser (group A) versus a similar method with the addition of lateral nail fold vaporization (group B).Outcome evaluation of a modified laser treatment modality for ingrowing toenails and determination of the role of lateral fold vaporization in reducing the recurrence of symptoms.Forty patients (mean age 32.45 years) were treated with CO2 laser ablation of toenails between 1999 and 2005 by four physicians. One physician implemented a method that includes lateral nail fold vaporization and resection of the nail segment with its nail bed from 1999 to 2005. Three physicians implemented a similar technique but without lateral fold vaporization between 1999 and 2003, and added lateral fold vaporization to the performed procedure starting in 2004.The recurrence rate was 37.5% in group A and 6.2% in group B. The overall average disease-free follow-up period was 42.2 months.The use of CO2 laser in the treatment of ingrowing toenails offers an effective modality. We demonstrate the importance of lateral fold vaporization with the CO2 laser both in improving efficacy and in decreasing recurrence rates over a long follow-up period.

Terror attacks have changed in the past decade, with a growing tendency toward explosives and suicide bombings, which led to a rise in the incidence of thermal injuries among victims. The Israeli-Palestinian conflict of October 2000 marked a turning point when an organized terror campaign commenced. This article presents data of terror-associated burns from the Israeli National Trauma Registry (ITR) during the years 1997 to September 2000 and October 2000 to 2003.We analyzed demographic and clinical characteristics of 219 terror-related burn patients and 6,546 other burn patients admitted to hospitals in Israel between 1997 and 2003. Data were obtained from the ITR.Burns contributed about 9% of all terror related trauma and about 5% of all other trauma (p0.0001). These percentages have not changed significantly before and after October 2000. Terror-related burns afflict Jewish males more than predicted by their percentage in the population, whereas other burns afflict non-Jewish males more than predicted. Adults and young adults (15-59 years) are the predominant group in terror-related burns (80%), whereas children younger than 15 years are the predominant group in other burns (50%). Large burns (20% to 89% total body surface area) are more common in terror casualties, with greater mortality (6.4% in terror-related versus 3.4% in others; p = 0.0258).Although the incidence of burns has risen because of an organized campaign, this change was noticeable in other trauma forms as well in similar proportions. Terror-related burns afflict a targeted population, and generally take on a more severe course with greater mortality rates, thus requiring appropriate medical treatment.

Background: The Aptos thread technique is a mode of uplifting the flabby soft tissue of the aging face. Permanent suture material made of polypropylene monofilament with dents is used in this technique. This procedure is gaining popularity throughout the world. According to the literature, several hundred Aptos procedures have been performed, and no major complications have been reported yet. Methods: Two adult women presented shortly after the Aptos thread insertion. They sustained devastating results. A close study was performed to understand and learn the potential complications. Results: The authors present two major complications, a rare case of Stensen's duct laceration and a case of chronic inflammation mandating surgical treatment. Conclusions: Describing complications may teach plastic surgeons more about this method and how to avoid similar devastating side effects in the future.

Venous malformations (VM) are developmental errors comprised of enlarged dysplastic blood vessels. Clinically they manifest as either a faint blue patch or a soft blue vascular mass. Treatment options include a sclerosing agent (such as alcohol or ethiblock), surgery or laser therapy. A review of the literature concerning VM and laser treatment yielded a few sporadic reports describing series of 3 to 46 cases. In this retrospective study we reviewed the files of the relevant cases. The data included the extent of the lesion, the different anatomical sites, age of patient and the extent of clearance of the lesion as the treatment's end point. This study includes 56 cases which makes it the largest series presented. The success rate of laser treatment was 92.8%. The immediate complication rate was very low (approximately 3.57%) including minimal scarring and deformity. No long term complications were noted. Our study concludes that treatment of VM is a difficult task due to the nature of the lesions. Laser treatment of these lesions enables one to obtain good results with a very low incidence of complications. Surgery and other treatment modalities are not always satisfactory, yield similar or less efficient results and have a higher complication rate. Laser treatment can play an important role in the treatment of VM and in fact may be the treatment of choice in some settings.

Background The purpose of this study was to investigate a means of providing pain relief during repair of facial lacerations in children in the emergency room. Methods This study was conducted in the emergency room of a tertiary care, university-affiliated hospital. Fifty percent nitrous oxide was administered by the surgeon who sutured the laceration. A nurse monitored the child throughout the procedure. At the end of the procedure, pain scores were evaluated by the surgeon and nurse using the FLACC (face, legs, activity, cry, and consolability) scale, a structured observational-behavioral scale for measurement of pain. Results Sixty patients between the ages of 1 and 16 years participated in the study. Of these, 15 were sutured using standard care (lidocaine infiltration), and 45 children received nitrous oxide in addition to lidocaine infiltration. Nitrous oxide was administered for an average of 11.9 +/- 5.1 minutes (range, 4 to 30 minutes). Forty-three children recovered to preprocedure activity in less than 1 minute. Two children recovered in less than 3 minutes. Average FLACC scores during infiltration and suturing were significantly lower in the nitrous oxide group compared with controls (infiltration, 1.9 of 10 versus 9.7 of 10; suturing, 2 of 10 versus 8.8 of 10). Forceful restraining was necessary in all the controls, whereas in the nitrous oxide group mild force was required in only 15 percent. Seventy percent of the children receiving nitrous oxide had no side effects. Vomiting and nausea were the most common (17 percent), transient side effects. No respiratory or cardiovascular side effects occurred. Conclusions Nitrous oxide can be safely administered by plastic surgeons while suturing facial lacerations in the emergency room. The fast onset and rapid recovery characteristics of nitrous oxide provide a convenient environment for performing short surgical procedures. This safe method for provision of analgesia and anxiolysis may be appealing to plastic surgeons for ambulatory procedures (e.g., suture removal, expander inflation, Botox injection, injection of various fillers) in pediatric and adult populations.

Postoperative sternal wound infection remains a significant complication and generally causes considerable morbidity and mortality. Macrophages play a major role in the process of wound healing. In order to evaluate the efficacy of local injection of activated macrophage suspensions into open infected sternal wound space, a retrospective case-control study was conducted. Sixty-six patients with deep sternal wound infection treated by activated macrophages (group 1) and 64 patients with deep sternal wound infection treated by sternal reconstruction surgery with various regional flaps (group 2), were matched for gender, age, and risk index. In up to 54 months of follow-up of group 1, 60 patients (91%) achieved complete wound closure. Two (3%) late deaths occurred unrelated to the procedure. Mortality rate in group 2 was 29.7% (19/64). Duration of hospitalization was 22.6 days in group 1 vs. 56.2 days in group 2. Patients with deep sternal wound infection following open heart surgery that were treated by activated macrophages had significantly less mortality as well as significant reduction of hospitalization in comparison to the surgically treated group. These results illustrate the advantages of using a biologically based activated macrophage treatment.

Objectives Mitomycin C (MC) is an anti-neoplastic agent with an anti-proliferative effect on fibroblasts. We set out to evaluate the effect of MC application following keloid excision. Study design and setting Patients with keloid in a tertiary referral center were enrolled in a prospective study. The scar was excised and prior to skin closure, a pledget with 1 cc of MC 0.4 mg/mL was applied for 5 minutes. Patient satisfaction and keloid thickness were assessed. Results All patients were satisfied with the results, although complete disappearance of the keloid was evident only in two. Keloid thickness was measured and ranged from 5 to 26 mm. Following surgery and treatment at 2 months thickness ranged from 0 to 8 mm. Conclusions MC application following scar resection appears to be effective in treatment of keloid. Significance As no specific effective treatment for keloid is currently available, utilization of this readily available therapeutic agent may improve treatment outcome.

The purpose of this study is to demonstrate feasibility of using our novel concept, termed competitive quenching, for protecting the choroidal extravascular compartment and retinal pigment epithelium (RPE) from verteporfin (VP)-induced phototoxicity using hypericin. Furthermore, we aim to achieve partitioning of the quencher, hypericin, in the extravascular space and VP within the microvascular compartment of the chorio-retinal complex in vivo.We protect RPE cells from damage inflicted by photoactivated VP by introducing hypericin into these cells prior to photosensitization to quench the photosensitizing activity of VP. Cell protection levels were measured by MTT and Hemacolor viability assays. Wavelength range used for VP photoexcitation (700 +/- 40 nm) excludes the absorption range of hypericin, preventing the latter from photoactivation. Pharmacokinetic conditions, in which hypericin spreads throughout the choroidal and retinal extravascular space while VP is confined to the vasculature, are delineated using double-fluorescence imaging.Cell viability increased 3- to 5-fold when 10-20 microM hypericin were present in RPE cells during photosensitization with 0.1-0.5 microM VP. VP fluorescence intensity was unchanged by the presence of hypericin in the cells. Hypericin administered intravenously to rats was confined to the choroidal vasculature after 15 min to 2 hr. Subsequently, hypericin partitioned to the choroidal and retinal extravascular space. VP administered at this time was confined to the microvasculature.RPE and choroid may potentially be protected by compartmentalizing hypericin to the extravascular compartment while VP administered shortly before photosensitization is confined to the microvasculature. Adverse photodynamic therapy (PDT) damage to choroidal tissues adjacent to neovasculature targeted for photoablation have the potential of being prevented by competitive quenching with hypericin.

To evaluate the use of diffusion-weighted magnetic resonance (MR) imaging with standard and high b values for pretreatment prediction and early detection of tumor response to various antineoplastic therapies in an animal model.Mice bearing C26 colon carcinoma tumors were treated with doxorubicin (n = 25) and with aminolevulinic acid-based photodynamic therapy (n = 23). Fourteen mice served as controls. Conventional T2-weighted fast spin-echo and diffusion-weighted MR images were acquired once before therapy and at 6, 24, and 48 hours after treatment. Pretreatment and early (1-2 days) posttreatment water diffusion parameters were calculated and compared with later changes in tumor volumes measured on conventional MR images by using the Pearson correlation test.In chemotherapy-treated tumors, a significant correlation (P.002, r = 0.6) was observed between diffusion parameters that reflected tumor viability, measured prior to treatment, and changes in tumor volumes after therapy. This correlation implies that tumors with high pretreatment viability will respond better to chemotherapy than more necrotic tumors. In tumors treated with photodynamic therapy, no such correlation was found. Changes observed in water diffusion 1-2 days after treatment significantly correlated with later tumor growth rate for both therapies (P.002, r = 0.54 for photodynamic therapy; P.0003, r = 0.61 for chemotherapy).High-b-value diffusion-weighted MR imaging has potential use for the early detection of response to therapy and for predicting treatment outcome prior to initiation of chemotherapy.

This paper presents an innovative method for the treatment of refractory wounds, starting with a blood unit, that is based on a biological approach. Local wound repair is one of the major unresolved clinical problems. Age, infection, clinical conditions such as diabetes mellitus, cardiac, renal, lung and liver failure, malnutrition and immunological deficiencies are among the reasons for wound repair delay or failure. Many chronic ulcers resist conventional treatment and do not heal for months and years, thus causing substantial morbidity and even mortality. The method for macrophage suspension treatment consists of introducing into the wound live cells that play a major role in the process of wound healing. The suspension is prepared from a blood unit of a healthy donor in a cost-effective, closed, sterile system. In the process of preparation, the macrophages are activated by hypo-osmotic shock to enhance their various functions in wound repair. The cells are applied to the wound either by local injection or by direct deposition into the wound. In most cases (90%), only one treatment is sufficient. Since 1995, macrophage suspensions have been used successfully in more than 1000 patients in several hospitals in Israel, without any side effects. Our results show that the use of a macrophage suspension is a safe and effective therapeutic strategy that shortens the healing period, reduces risk of complications and morbidity and improves the quality of life for long-suffering patients. This treatment requires no hospitalization and can be given on an ambulatory basis.

Cancer cells of different solid and hematopoietic tumors express growth factors in respective stages of tumor progression, which by autocrine and paracrine effects enable them to grow autonomously. Here we show that the murine B16 melanoma cell line and two human primary cultures of stomach adenocarcinoma and glioblastoma multiforme (GBM) constitutively secrete interleukin (IL)-10 in an autocrine/paracrine manner. This cytokine is essential for tumor cell proliferation because its neutralization decreases clonogenicity of malignant cells, whereas addition of recombinant IL-10 increases cell proliferation. The immunomodulator ammonium trichloro(dioxoethylene-o,o′)tellurate (AS101) decreased cell proliferation by inhibiting IL-10. This activity was abrogated by exogenous addition of recombinant IL-10. IL-10 inhibition by AS101 results in dephosphorylation of Stat3, followed by reduced expression of Bcl-2. Moreover, these activities of AS101 are associated with sensitization of tumor cells to chemotherapeutic drugs, resulting in their increased apoptosis. More importantly, AS101 sensitizes the human aggressive GBM tumor to paclitaxel both in vitro and in vivo by virtue of IL-10 inhibition. AS101 sensitizes GBM cells to paclitaxel at concentrations that do not affect tumor cells. This sensitization can also be obtained by transfection of GBM cells with IL-10 antisense oligonucleotides. Sensitization of GBM tumors to paclitaxel (Taxol) in vivo was obtained by either AS101 or by implantation of antisense IL-10-transfected cells. The results indicate that the IL-10 autocrine/paracrine loop plays an important role in the resistance of certain tumors to chemotherapeutic drugs. Therefore, anti-IL-10 treatment modalities with compounds such as AS101, combined with chemotherapy, may be effective in the treatment of certain malignancies.

Background: Interventional magnetic resonance imaging (iMRI) has the potential for guiding interventional cardiac procedures in real time. Objectives: To test the feasibility of iMRI guided gene and cell transfer to the heart and to monitor myocardial remodelling after myocardial infarction in a rat model. Methods: The MRI contrast agent GdDTPA, together with either Evans blue dye, or a recombinant adenovirus encoding the LacZ gene, or primary fibroblasts tagged by BrdU, were injected into the myocardium of rats under iMRI guidance. Rats were killed seven days after the injection and the hearts sectioned to identify the blue dye, LacZ expression, or fibroblast presence, respectively. In a parallel study, left ventricular area was measured before and after myocardial infarction and in sham operated rats by T1 weighted MRI and by echocardiography. Results: Location of GdDTPA enhancement observed with iMRI at the time of injection was correlated with Evans blue stain, β-gal expression, and the primary fibroblast location in histological studies. iMRI and echocardiography measured a comparable increase in left ventricular area at seven and 30 days after myocardial infarction. A good correlation was found between the iMRI and echocardiographic assessment of left ventricular area ( r = 0.70; p < 0.0001) and change in left ventricular area with time ( r = 0.75; p < 0.0001). Conclusions: The results show the feasibility and efficiency of iMRI guided intramyocardial injections, and the ability to monitor heart remodelling using iMRI. Genes, proteins, or cells for tissue engineering could be injected accurately into the myocardial scar under iMRI guidance.

The purpose of this study was to investigate the relationship between a decrease in the peripheral fat content by suction-assisted lipectomy (SAL) and serum leptin levels. Twenty-two healthy females who underwent SAL for aesthetic reasons participated in the study. The data included height, weight, dietary habits, and leptin levels before surgery and at 1 and 6 weeks postoperatively. The aspirate ranged between 1000 and 6000 ml, with an average of 2700 ml. Thirteen patients with an aspirate of over 2700 ml all experienced an immediate postoperative decrease in appetite which returned gradually by 12 to 17 days postoperatively. They lost an average of 7% of the total body weight at 6 weeks. The leptin levels 1 week postoperatively were significantly lower than the preoperative levels (p < 0.01); at 6 weeks the decrease in leptin level was not statistically significant. In conclusion, a reduction of the peripheral fat content of more than 2700 ml by SAL has an immediate effect on leptin levels that lasts at least 1 week and correlates with voluntary changes in energy intake.

Background. Mohs surgery and other surgical techniques are used for the removal of squamous cell carcinoma of the lower lip and may leave a large defect in the vermilion and underlying tissue. When nearly the entire lower lip is excised, reconstruction of this defect is a challenge. Repair requires the matching of vermilion color, maintenance of oral sphincter function and mouth opening size, and retention of sensation. Several techniques have been suggested. We present a modification of the Webster flap for total lower lip reconstruction using innervated muscle-bearing flaps. Objective. To present a surgical technique for the reconstruction of total lower lip defects after excision of squamous cell carcinoma. Methods. Innervated muscle-bearing flaps are used and demonstrated in one case. The surgical technique is discussed in detail. Results. The reconstructive results were excellent. There were no postoperative complications. Conclusion. The use of innervated muscle-bearing flaps is a useful and effective option for the reconstruction of total lower lip defects.

Background. The nasolabial flap is a versatile and effective option for the closure of nasal defects of the cheek and nasal sidewall following Mohs surgery. However, both extirpation of a tumor in the region of the base of the flap or previous use of the flap often destroy the proximal axial blood supply to the flap, excluding its immediate utilization. We describe a different use of the nasolabial flap and a technique for preserving its capacity in the case of reutilization Objective. To describe the versatility of the nasolabial flap and a delay procedure that enables its exploitation despite prior disruption of the proximal blood supply. Methods. Three different uses of the same nasolabial flap are demonstrated in one patient. The surgical techniques are discussed in detail. Results. The reconstructive results were excellent. There were no postoperative complications. Conclusion. The nasolabial flap is a versatile and effective option for the closure of nasal defects of the cheek and nasal sidewall. When the nasolabial flap has been used before, or its blood supply compromised, the delay procedure can reestablish its applicability.

Background and Objective Rhinophyma is a benign, disfiguring disorder of the nose which presents the end stage of acne rosacea, and can also occasionally result in nasal airway obstruction. We describe the first series of patients treated with Erbium laser. Study Design/Materials and Methods Severe-to-moderate rhinophyma in six patients were treated at our institution between 1995 and 1996, using the Erbium:YAG (Erb:YAG) laser. Results All patients achieved marked cosmetic improvement, with no complications. Post-operative healing time was seven to fourteen days-significantly shorter than similar other modalities. Conclusions The Erbium laser provides very accurate tissue ablation and allows the sculpturing of the hypertrophied areas, offering good cosmetic results, with a very short healing period as shown in our study. Lasers Surg. Med. 29:230–235, 2001. © 2001 Wiley-Liss, Inc.

Pulsed photothermic treatment (PTT) of pigmented B16 mice melanoma tumors was carried out using a Photodyne incoherent light delivery system. Tumor heating with average temperature of 41-44 degrees C was observed during broadband photoirradiation (600-800 nm) at light doses of 60-120 J/cm(2) delivered using 0.6 J/cm(2) pulses (2 ms) at 1 Hz repetition rate. Electron microscopy of tumor samples revealed pronounced structural changes in microvasculature and melanosomes. Pulsed PTT caused damage to endothelial cells and vascular walls, swelling of mitochondria and melanosomal disruption without nuclear alteration. Significant tumor response with necrosis formation followed by tumor regression was observed by a tumor growth study after PTT at 120 J/cm(2).

Thoughthe riskof magnetic resonanceimaging(MRI)inducedburns has been previously published, the overwhelmingnature of this injury combined with its preventable etiology,merit reiteration of the morbidity associated with the use ofnon-MR-compatible devices in MRI sessions. After describingthe patient details, we provide guidelines aimed at decreasingthe potential risk of burns during routine magnetic resonanceimaging.MRI scans expose the patient to electromagnetic (EM)radiation. The EM spectrum contains non-ionizing radiationwhichdoesnotcauseirreversiblecelldamage[1].Itis,however,capable of inducing thermal damage. Various devices wereshown to induce burns in MRI settings. The list includes smallcircularmetallicimplantsinrabbits[2],tattoos[3,4],deepbrainimplanted stimulators [5], halo pins [6], cylindrical and otherimplanted devices [7], EKG monitoring devices [8],andtransdermal patches [9]. Previous studies have shown thatsubstantial heating (with temperature elevation up to 63.1 8C)[10]can becausedbyaresonantconducting loopcoupledtoaninduced EM field [11]. This situation occurs when inductanceand capacitance are equal and opposite: a state which can besustainedbyaconductingwirewithinthemagneticfieldsofanactive MR session. It is further speculated that several wiresbundled together in a linear arrangement are also capable ofthermal damage through a similar mechanism [15].

BACKGROUND: An incident of fatal pericardial bleeding immediately after the extraction of a sternal wire prompted a search for the most appropriate method for removing sternotomy wire sutures. A model sternum was devised to explore this problem, and several commonly used techniques for wire extraction were evaluated. METHODS: A wooden sternal model was constructed to simulate the dimensional properties of a sternum overlying the mediastinal cavity, and to imitate its tensile characteristics. A Monofil CrNi-316L (Johnson & Johnson, Brunswick, NJ, USA), No. 7 CCS, 9 metric, 4x45-cm wire was passed vertically through drilled holes. The suture was then crossed and pulled, thus joining the two boards and approximating the wire to their deep surface. A latex balloon filled with dye was placed inside under the boards. Wire holders were used to extract the wires, using a linear pulling technique and a coiling around the wire-holder tip technique. Sixty repetitions were performed for each method. RESULTS: In 60 trials of direct linear wire pulling, balloon rupture occurred in 33 (55%), whereas tearing was noted only 15 times out of 60 attempts (25%) when the tense coiling method was used. CONCLUSIONS: Sternotomy wire sutures should be extracted using a controlled technique that ensures safety to vital tissues in close proximity to the sternal bone. The tense coiling procedure offers superior safety when compared to the direct pulling process, demonstrated by a lower incidence of balloon rupture because of the lesser degree of wire flexure. This technique has become the method of choice in our medical center.

The interaction of photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) and hyperthermia is not well understood. In the present study, significant enhancement of tumor damage was observed after simultaneous application of ALA-PDT and IR-induced hyperthermia using a broad-band incoherent light source. One hour after systemic administration of ALA at a dose of 200 mg/kg, subcutaneously transplanted C26 colon carcinoma tumors were irradiated with two bands of the VersaLight system, red (R, 580-720 nm) and red plus IR (R + IR, 580-720 nm and 1250-1600 nm). Photoirradiation using the R + IR band at different fluence rates and exposures caused mild heating of the tumor to 39-43 degrees C at a 3 mm depth. Electron microscopy after ALA + R, ALA + R + IR and R + IR treatments showed early mitochondrial swelling that was more pronounced in the ALA + R + IR group. Tumor necrosis assessment, using histology and vital staining, revealed an enhancement of tumor necrosis depth in the ALA + R + IR group compared to ALA + R and R + IR. The results showed that subhyperthermic heating to 39-39.5 degrees C in the ALA + R + IR group decreased the threshold light dose required for 100% tumor necrosis from 210 J/cm2 (observed in the ALA + R group) to 140 J/cm2. A tumor growth delay test, based on tumor volume measurement, also revealed significant enhancement of antitumor effect after application of ALA + R + IR compared to ALA + R.

Partial lateral nasal defects challenge the plastic surgeon both technically and aesthetically. Many methods for reconstruction of these defects have been described. We have used a turnover forehead flap in conjunction with composite auricular graft for the reconstruction of nasal defects. The forehead flap is turned over so that the forehead skin serves as internal lining in the nose. The composite auricular graft serves as external nasal lining and provides mechanical support to the ala. The technique was used in seven patients and is presented here with illustrations, selected cases, results, and conclusions concerning patient selection.

The spectroscopic and biological properties of the new photosensitizer lutetium texaphyrin (Lu-Tex) were assessed in vitro and in vivo on a C26 colon carcinoma model, in comparison with hematoporphyrin (Hp), photofrin II (PII) and chlorin e 6( Chl ). Strong binding of Lu-Tex to lipid bilayer membranes was observed. The results of confocal fluorescence microscopy on C26 cells showed that Lu-Tex was localized in small vesicles in the cytoplasm, possibly in the lysosomes, while Chl and Hp were distributed in larger cytoplasmic vesicles attributed to mitochondria. Scanning electron microscopy and X-ray microanalysis revealed that photodynamic therapy with Lu-Tex induced only slight damage to the cell membrane, leading to a delayed cell response. Chl and Hp caused significant structural damage to the outer cell membrane, resulting in ionic imbalance and fast cell death. The in vitro quantitative assessment of the relative efficiency per absorbed photon of the sensitizers revealed that Lu-Tex was less effective than Chl and Hp . However, the results of our in vivo study showed that at the same light and drug doses the anti-tumor efficiency of the agents was in the following order: Lu-Tex > Chl > PII . The strong in vivo anti-tumor effect of Lu-Tex can be explained by its higher integrated absorption in the long-wavelength range.

A novel spectral image-analysis system based on Fourier transformed spectroscopy combined with image processing has been used for the in vivo study of porphyrin localisation in human skin lesions. Fluorescence measurements were performed on patients with basal cell carcinomas (BCC) and acne. BCC lesions were examined after a 16-hour topical application of aminolaevulinic acid (ALA); for acne lesions, autofluorescence was studied. The results of fluorescence microscopy of BCC lesions revealed red fluorescence in the stratum corneum, epidermis, pilosebaceous units and in the tumour sites. The in vivo macroscopic examination showed higher protoporphyrin IX (PP) fluorescence in BCC lesions and in acne as compared to the surrounding normal tissue. An enhanced demarcation of the lesions' borders was obtained using the spectral similarity-mapping function.

The assessment of deuteroporphyrin-hemin complex as an agent for the treatment of burn wounds infected with a multiple-drug resistant strain of Staphylococcus aureus was performed. The effect of the porphyrin on the survival of the infectious bacteria was first assayed in culture, and later tested as well in a burned infected animal model. The addition of deuteroporphyrin and hemin, separately or together (as a complex) to a growing culture of S. aureus was monitored during 8 hours. It was found that deuteroporphyrin alone was strongly bactericidal only after photosensitization. On the other hand, hemin alone was moderately bactericidal but light independent. A combination of both deuteroporphyrin and hemin was extremely potent even in the dark and did not require illumination to eradicate the bacteria. The in vivo experiments by application of the above porphyrins in combination to infected burn wounds in guinea pigs was an effective way to reduce dramatically the contaminating S. aureus. Reduction of more than 99% of the viable bacteria was noted after the porphyrin mixture was dropped on the eschar or injected into the eschar, an effect that lasted for up to 24 hours. The deuteroporphyrin-hemin complex may be suggested as a new bactericidal treatment of S. aureus infected burns since it was found to be a potent and promising anti-Staphylococcal agent.

An in vivo fluorescence monitoring and photodynamic therapy (PDT) study was performed using the new photosensitizer lutetium texaphyrin (Lu-Tex). This photosensitizer is water soluble and has the additional advantage of strong absorption near 730 nm. C26 colon carcinoma was transplanted in the foot of BALB/c mice. In vivo fluorescence spectroscopy was applied to study Lu-Tex tissue distribution kinetics. For this purpose, fluorescence intensity both in the foot with the tumor and in the normal foot was measured in vivo by the laser-induced fluorescence (LIF) system. For PDT, both feet of the mice were irradiated simultaneously with the use of a new high intensity pulsed light delivery system, the Photodyne. The results of the LIF measurements showed that the maximal fluorescence intensity ratio between the normal and tumor bearing foot (FIR) was observed 24–48 h after the agent injection. Photoirradiation with doses from 90 to 240 J cm −2 (0.6 J cm −2 per 2 ms pulse, 1 Hz) 24 h after injection of Lu-Tex at a dose of 10 mg kg −1 caused significant tumor necrosis and delay in the tumor growth rate. The antitumor effect was enhanced with increasing light doses. Normal tissue response to PDT with Lu-Tex was determined as the damage index of the normal foot, which was irradiated simultaneously with the tumor bearing foot. The normal tissue response after PDT with Lu-Tex was compared with 5-aminolevulinic acid (ALA) induced protoporphyrin IX (PP), chlorin e 6 (Chl) and Photofrin (PII) at the same values of antitumor effect. The results showed that at 50, 80 and 100% inhibition of tumor growth the orders of the values of normal foot damage indexes were as follows: ALA > Lu-Tex ≥ PII > Chl, PII > ALA > Lu-Tex > Chl and PII > Lu-Tex > ALA > Chl respectively.

Rhinoplasty is rarely complicated with infection. We present a case of necrotizing periorbital cellulitis that developed in an 18-year-old woman following aesthetic rhinoplasty. The clinical manifestations consisted of swelling of the eyelids and necrosis of the lower eyelid regions, accompanied by high fever. Streptococcus pyogenes was isolated from the wound. The patient responded well to administration of intravenous amoxycillin/clavulanate and conservative local treatment. The infection resolved uneventfully. At 2-year follow-up, the cosmetic result was excellent.

An in vivo study of tissue distribution kinetics and photodynamic therapy (PDT) using 5-aminolaevulinic acid (ALA), chlorin e6 (Chl) and Photofrin (PII) was performed to evaluate the selectivity of porphyrin accumulation and tissue damage effects in a tumour model compared with normal tissue. C26 colon carcinoma of mice transplanted to the foot was used as a model for selectivity assessment. Fluorescence measurements of porphyrin accumulation in the foot bearing the tumour and in the normal foot were performed by the laser-induced fluorescence (LIF) system. A new high-intensity pulsed light delivery system (HIPLS) was used for simultaneous irradiation of both feet by light in the range of 600-800 nm, with light doses from 120 to 300 J cm-2 (0.6 J cm-2 per pulse, 1 Hz). Photoirradiation was carried out 1 h after injection of ALA, 3 h after injection of Chl and 24 h after injection of PII. A ratio of porphyrin accumulation in tumour vs normal tissue was used as an index of accumulation selectivity for each agent. PDT selectivity was determined from the regression analysis of normal and tumour tissue responses to PDT as a function of the applied light dose. A normal tissue damage index was defined at various values (50, 80 and 100%) of antitumour effect. The results of the LIF measurements revealed different patterns of fluorescence intensity in tumour and normal tissues for ALA-induced protoporphyrin IX (ALA-PpIX), Chl and PII. The results of PDT demonstrated the differences in both anti-tumour efficiency and normal tissue damage for the agents used. The selectivity of porphyrin accumulation in the tumour at the time of photoirradiation, as obtained by the LIF measurements, was in the order ALA-PpIX > Chl > PII. PDT selectivity at an equal value of anti-tumour effect was in the order Chl > ALA-PpIX > PII. Histological examination revealed certain differences in structural changes of normal skin after PDT with the agents tested. The results of PDT selectivity assessment with respect to differences in mechanisms of action for ALA, Chl and PII are discussed. Images Figure 3 Figure 4

Topical 5-aminolevulinic acid (ALA) application in three different creams was carried out on mice bearing subcutaneously transplanted C26 colon carcinoma. The creams contained (a) 20% ALA alone, (b) ALA with 2% dimethylsulphoxide (DMSO) and (c) ALA, DMSO and 2% edetic acid disodium salt (EDTA). Protoporphyrin IX (PP) production in the tumour and in the skin overlying the tumour was studied by two methods: laser-induced fluorescence (LIF) and chemical extraction. The kinetics of PP production in the skin and in the tumour, as studied by the LIF method, was similar for all three cream preparations. The PP fluorescence intensity in the tissues reached its maximum 4-6 h after application of the creams. Quantitative analysis showed that the PP concentration after treatment was more pronounced in the skin than in the tumour. The efficiency of porphyrin production in the skin by the creams used was in the following order: ALA-DMSO-EDTA > ALA-DMSO > ALA. In the tumour the enhancing effect of DMSO and EDTA on PP accumulation induced by ALA was observed mainly in the upper 2 mm section. However, the concentration of PP in the tumour was found to be approximately the same for ALA-DMSO and ALA-DMSO-EDTA cream combinations. The possible mechanisms of the effect of DMSO and EDTA are discussed.

BackgroundPsoriasis is a complex disease at the cellular, genomic and genetic levels. The role of microRNAs in skin development was shown in a keratinocyte-specific Dicer knockout mouse model. Considering that two main characteristics of psoriasis are keratinocytes hyperproliferation and abnormal skin differentiation, we hypothesized that aberrant microRNA expression contributes to the psoriatic phenotype. Here, we describe the differential expression of miRNAs in psoriatic involved and uninvolved skin as compared to normal skin, revealing an additional aspect of this complex disorder.Methodology/principal findingsExpression arrays were used to compare microRNA expression in normal skin versus psoriatic involved and uninvolved skin. Fourteen differentially expressed microRNAs were identified, including hsa-miR-99a, hsa-miR-150, hsa-miR-423 and hsa-miR-197. The expression of these microRNAs was reevaluated by qPCR. IGF-1R, which is involved in skin development and the pathogenesis of psoriasis, is a predicted target of hsa-miR-99a. In an in situ hybridization assay, we found that IGF-1R and miR-99a are reciprocally expressed in the epidermis. Using a reporter assay, we found that IGF-1R is targeted by hsa-miR-99a. Moreover, over expression of miR-99a in primary keratinocytes down-regulates the expression of the endogenous IGF-1R protein. Over expression of miR-99a also inhibits keratinocyte proliferation and increases Keratin 10 expression. These findings suggest that overexpression of hsa-miR-99a in keratinocytes drives them towards differentiation. In primary keratinocytes grown in high Ca(++), miR-99a expression increases over time. Finally, we found that IGF1 increases the expression of miR-99a.Conclusions/significanceWe identified several microRNAs that are expressed differentially in normal and psoriatic skin. One of these miRNAs is miR-99a that regulates the expression of IGF-1R. Moreover, miR-99a seems to play a role in the differentiation of keratinocytes. We suggest that miR-99a is one of the regulators of the IGF-1R signaling pathway in keratinocytes. Activation of IGF1 signaling results in elevation of miR-99a which represses the expression of IGF-1R.

Introduction : Fractional ablative and non-ablative lasers have gained popularity in the treatment of acne scars and rhytids due to their effi cacy and improved tolerability. Plasma and radio frequency (RF) have also emerged as methods for ablative or non-ablative energy delivery. We report preliminary experience with a novel fractional micro-plasma RF device for the treatment of facial acne scars and rhytids. Methods : Sixteen patients with facial acne scars or rhytids were treated at 4-week intervals. Treatment parameters were titrated to an immediate end point of moderate erythema. The clinical end point for cessation of treatment was the attainment of satisfactory clinical results. Results were monitored photographically up to 3 months after treatment. Results : Acne scars showed marked improvement after two to four treatments. Facial rhytids dem- onstrated reduced depth after two treatments and marked improvement after four treatments. Treatment was well tolerated by all participants, with transient erythema and short downtime. These results provide initial evidence for the safety and effectiveness of fractional micro-plasma RF as a low-downtime and well-tolerated modality for the treatment of acne scars and facial rhytids.

The objective of this study was to compare local injections of AMS with SOC treatments for stage III and IV pressure ulcers in elderly patients. It was designed as historically prospective 2-arms non-parallel open controlled trial, and conducted in a department of geriatric medicine and rehabilitation of a university affiliated tertiary hospital. We studied 100 consecutive elderly patients with a total of 216 stage III or IV pressure ulcers, 66 patients were assigned to the AMS group and had their wounds injected, while 38 patients were assigned to the SOC group. Primary outcome was rate of complete wound closure. Time to complete wound closure and 1-year mortality served as secondary outcomes. Statistical analyses were performed at both patient and wound levels. Percentage of completely closed wounds (wound level and patient level) were significantly better (p

Background NK cells are key players in anti tumor immune response, which can be employed in cell-based therapeutic modalities. One of the suggested ways to amplify their anti tumor effect, especially in the field of stem cell transplantation, is by selecting donor/recipient mismatches in specific HLA, to reduce the inhibitory effect of killer Ig-like receptors (KIRs). Here we suggest an alternative approach for augmentation of anti tumor effect of allogeneic NK cells, which is founded on profile matching of donor NK lysis receptors (NKLR) phenotype with tumor lysis-ligands. Methodology/Principal Findings We show that an NKLR-mediated killing directly correlates with the NKLR expression intensity on NK cells. Considerable donor variability in the expression of CD16, NKp46, NKG2D and NKp30 on circulating NK cells, combined with the stability of phenotype in several independently performed tests over two months, indicates that NKLR-guided selection of donors is feasible. As a proof of concept, we show that melanoma cells are dominantly recognized by three NKLRs: NKG2D, NKp30 and NKp44. Notably, the expression of NKp30 on circulating NK cells among metastatic melanoma patients was significantly decreased, which diminishes their ability to kill melanoma cells. Ex vivo expansion of NK cells results not only in increased amount of cells but also in a consistently superior and predictable expression of NKG2D, NKp30 and NKp44. Moreover, expanded NK cultures with high expression of NKG2D or NKp30 were mostly derived from the corresponding NKG2Dhigh or NK30high donors. These NK cultures subsequently displayed an improved cytotoxic activity against melanoma in a HLA/KIR-ligand mismatched setup, which was NKLR-dependent, as demonstrated with blocking anti-NKG2D antibodies. Conclusions/Significance NKLR/NKLR-ligand matching reproducibly elicits enhanced NK anti-tumor response. Common NKLR recognition patterns of tumors, as demonstrated here in melanoma, would allow implementation of this approach in solid malignancies and potentially in hematological malignancies, either independently or in adjunction to other modalities.