Cutaneous Toll-like Receptor 9 Pre-Defines Hydroxychloroquine Dosage in Patients with Both Discoid and Subacute Lupus Erythematosus.

Background and Objectives: Cutaneous lupus erythematosus (CLE) presents clinically heterogeneous manifestations, partially explained by the different expression of Toll-like receptors (TLRs) type 8 and 9, located to endosomal compartments where they are poised to recognize microbial nucleic acids. This disease is empirically treated with hydroxychloroquine (HCQ), which is hallmarked with a safe and effective profile, but induces a slow and sometimes clinically insufficient therapeutic response. Currently, no biomarkers predictive of response are validated or even proposed in the scientific literature. We aimed to evaluate endosomal TLR type 7, 8 and 9 as predictive biomarkers of HCQ efficacy. Materials and Methods: We conducted a case-control study comparing CLE patients retrospectively assigned to three subgroups based on 3-6-month Cutaneous LE Disease Area and Severity Index (CLASI) reduction upon treatment with HCQ (I = <40% vs. II = 40-80% vs. III = >80%). Before HCQ, lesional skin specimens were collected in untreated CLE and through immunohistochemistry; TLR-7, -8 and -9 expression was evaluated in the epidermis and the lymphocytic infiltrate was evaluated in the dermis. Results: Sixty-six lesional skin biopsies were compared with healthy controls. CLE patients displayed lower epidermal expression of total TLR 8 and 9 as well as infiltrating TLR-8, TLR9 + lymphocytes compared to controls. High HCQ responders differed from low responders for TLR-9 positivity (high vs. low) and for the lymphocytic dermal infiltrate (high vs. low). Conclusions: TLR9 could be envisaged as a possible biomarker to predict HCQ response level and dosage in CLE patients.

Immediate Response to Brentuximab Vedotin in a Patient with Localized MF-LCT.

The large cell transformation of mycosis fungoides (MF-LCT) is a phenomenon observed in the advanced stages of mycosis fungoides (MF), which is the most common primary cutaneous lymphoma. The diagnostic criteria of MF-LCT are a minimum of 25% of large cells or a formation of microscopic nodules of them in the histological examination of skin samples. The clinical outcomes for MF-LCT are poor, as less than 20% of patients survive 5 years after diagnosis, but the expression of the CD30 antigen is generally considered to be associated with a better prognosis. We present a case of a patient with the diagnosis of MF with LCT, with an ulcerated tumor lesion approximately 30 × 20 cm in size on the right lateral abdominal wall. Brentuximab vedotin (BV) treatment was started due to the presence of the CD30 antigen, with a quick and impressive regression of the cutaneous lesion and tumor mass and good treatment tolerance. After follow-up of 20 months, patient remains in complete remission. A schedule of treatment for MF-LCT is directed mainly by the clinical stage of the disease and the comorbidities; the more severe clinical course of the disease requires systemic treatment. If at least 5% of the cells found in the skin lesions biopsy sample express the CD30 antigen, a beneficial effect of BV treatment could be expected. It may seem that the use of BV is one of the optimal therapeutic options in patients with advanced MF-LCT showing expression of CD30.

Distribution of DC Subtypes: CD83+, DC-LAMP+, CD1a+, CD1c+, CD123+, and DC-SIGN+ in the Tumor Microenvironment of Endometrial Cancers-Correlation with Clinicopathologic Features.

Treatment options for endometrial cancer (EC) do not provide satisfactory survival improvement for advanced cases, hence the interest in novel therapies utilizing immunological regulatory mechanisms. Measures to modify the functionality of dendritic cells (DCs) found in TME are intensively investigated, given that DCs play a crucial role in inducing antitumor immunity. Samples of malignant endometrial neoplasms obtained from 94 patients were immunohistochemically stained with selected antibodies. Counts of positively identified DCs were correlated with clinical advancement and histological malignancy of cancers. The most prominent DC subtypes were immature DC-SIGN+ or CD123+. Mature CD83+ DCs were the fewest. We found a significant divergence of grade value distribution between cancers of different DCs' CD1a+ counts. The DC-LAMP+ count was positively associated with grade. Cancers with the least DC CD1c+ or DC CD123+ had higher pT scores than ones that were more heavily infiltrated. ECs can suppress immune cells, hence the predominance of immature DCs in our samples. Associations between DC counts and clinicopathological features of EC were observed only for a few subsets, which was plausibly due to the low diversity of the obtained samples or the small group size. Predictive abilities of particular DC immune subsets within EC's TME remain ambiguous, which calls for further research.

Dendritic cells may help differentiate discoid lupus erythematosus alopecia from lichen planopilaris.

Introduction: Primary cicatricial alopecia (PCA) encompasses a heterogeneous group of inflammatory diseases characterized by the replacement of hair follicle structures by fibrous tissue. Discoid lupus erythematosus (DLE) and lichen planopilaris (LPP) are the most common causes of scarring alopecia. The distinction between both entities is often challenging because of significant clinical and histopathological overlap. Aim: We hypothesized that dendritic cells which are implicated in PCA pathogenesis can provide a reliable histopathological clue to distinguish between these two entities. Material and methods: In a retrospective cohort study including 51 patients diagnosed with LPP and DLE we mapped and quantified the distribution of dendritic cells. Cell count in lesional skin was performed on immunohistochemistry by using characteristic monoclonal antibodies to specific subpopulations of dendritic cells. Results: We demonstrated that almost all subpopulations of dendritic cells were highly expressed in lesional skin of discoid lupus erythematosus patients in comparison with lichen planopilaris ones. Conclusions: In the light of this observation, dendritic cells might be used as an additional clue in differential diagnosis of PCA.

Scalp vascularization as a marker of topical minoxidil treatment efficacy in patients with androgenetic alopecia.

Introduction: Androgenetic alopecia is the most common type of non-cicatricial hair loss both in male and female patients. The pathomechanism of the disease involves chronic and progressive miniaturization of hair follicles, which leads to the conversion of terminal hair to vellus hair. Minoxidil is a first-line drug in the treatment of female pattern hair loss (FPHL). Aim: The study is aimed at verifying whether the degree of scalp vascularization has an impact on the efficacy of topical 5% minoxidil treatment. Material and methods: The study involved a group of 76 patients diagnosed with FPHL, who underwent a scalp biopsy for a histological examination of their scalp vascularization. The patients were divided into two groups, with rich and poor scalp vasculature. In all patients, topical treatment with 5% minoxidil was applied for a minimum of 6 months, followed by video-trichoscopic assessment. Results: A significant increase in the total count was observed 6 months into the treatment as compared with baseline, and a decrease in the number of single hair per follicle. It was observed that the number of single hair units had gone down in 50.67% of patients. The study also demonstrated an increase in the total hair count in 57.33% of patients as well as no drops in the total count in 68% of patients, following 6 months of treatment. Conclusions: Patients responded equally well to the applied topical minoxidil treatment, irrespectively of the number of blood vessels in the scalp.

Molecular Proof of a Clinical Concept: Expression of Estrogen Alpha-, Beta-Receptors and G Protein-Coupled Estrogen Receptor 1 (GPER) in Histologically Assessed Common Nevi, Dysplastic Nevi and Melanomas.

Background and Objectives: Epidemiologic data show significant differences in melanoma incidence and outcomes between sexes. The role of hormonal receptors in the pathogenesis of melanocytic lesions remains unclear, thus we performed this study aiming to assess estrogen receptors expression in different melanocytic lesions. Materials and Methods: We performed a cross-sectional study that included 73 consecutively excised melanocytic lesions. Estrogen receptor alpha (ERα), beta (ERß), and G-protein coupled estrogen receptor (GPER) expression was analyzed in melanocytes and keratinocytes of common nevi, dysplastic nevi, melanoma, healthy skin margin, and in sebaceous and sweat gland cells. Results: ERß expression was higher in dysplastic nevi margin melanocytes compared to common nevi (p = 0.046) and in dysplastic nevi keratinocytes compared to melanoma keratinocytes (p = 0.021). ERß expression was significantly higher in margin melanocytes compared to melanoma melanocytes (p = 0.009). No difference in ERß expression was shown between melanocytes of three types of lesions. GPER expression was higher in nuclei and cytoplasm of dysplastic nevi (p = 0.02 and p = 0.036 respectively) and at the margin compared to melanoma. GPER expression was lower in sebaceous glands of tissue surrounding common nevi (p = 0.025) compared to dysplastic nevi. GPER expression was higher in skin margin tissue melanocytes (p = 0.016 nuclear, p = 0.029 cytoplasmic) compared to melanoma melanocytes. There were no differences in ERα expression between the melanocytic lesions. Conclusion: Further large-scale studies are warranted to investigate the potential role of ERß and GPER in the pathogenesis of melanocytic lesions.

Addressing the Osteoporosis Problem-Multifunctional Injectable Hybrid Materials for Controlling Local Bone Tissue Remodeling.

Novel multifunctional biomimetic injectable hybrid systems were synthesized. The physicochemical as well as biological in vitro and in vivo tests demonstrated that they are promising candidates for bone tissue regeneration. The hybrids are composed of a biopolymeric collagen/chitosan/hyaluronic acid matrix and amine group-functionalized silica particles decorated with apatite to which the alendronate molecules were coordinated. The components of these systems were integrated and stabilized by cross-linking with genipin, a compound of natural origin. They can be precisely injected into the diseased tissue in the form of a viscous sol or a partially cross-linked hydrogel, where they can serve as scaffolds for locally controlled bone tissue regeneration/remodeling by supporting the osteoblast formation/proliferation and maintaining the optimal osteoclast level. These materials lack systemic toxicity. They can be particularly useful for the repair of small osteoporotic bone defects.

COVID-19 Autopsies: A Case Series from Poland.

This paper presents autopsy findings of 3 COVID-19 patients randomly selected for post-mortem from two tertiary referral Polish hospitals. Analysis of macroscopic, histopathological findings with clinical features was performed. All 3 deceased patients were Caucasian males (average age 61 years, range from 56 to 68 years). Using real-time polymerase chain reaction assay, the patients were confirmed (antemortem) to have severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Two patients were obese, and 1 patient had type 2 diabetes mellitus. The medical history of 1 patient included hemorrhagic pancreatitis, gangrenous cholecystitis, Acinetobacter baumanii sepsis, and cholecystectomy. Pulmonary embolism was diagnosed in 2 patients. At autopsy, in 1 case, the lungs showed bilateral interstitial pneumonia with diffuse alveolar damage (DAD), while in another case, interstitial pulmonary lymphoid infiltrates and enlarged atypical pneumocytes were present but without DAD. Microthrombi in lung vessels and capillaries were observed in 2 cases. This study revealed thrombotic complications of COVID-19 and interstitial pneumonia with DAD presence as the main autopsy findings in patients with SARS-CoV-2 infection that was confirmed antemortem with molecular tests. Autopsy studies using tissue sections handled in accordance with SARS-CoV-2 biosafety guidelines are urgently needed, especially in the case of subjects who were below the age of 60.

Dendritic cells as predictive markers of responsiveness to hydroxychloroquine treatment in primary cicatricial alopecia patients.

Primary cicatricial alopecia (PCA) encompasses a diverse group of inflammatory diseases characterized by the irreversible replacement of hair follicle structures by fibrous tissue. Although the pathogenesis of PCA remains not fully understood, the key to its understanding might be the location of dendritic cells (DCs) inflammatory infiltrate. One of the systemic therapy of choice in PCA patients is hydroxychloroquine (HCQ). We hypothesized that DCs are implicated in PCA pathogenesis and that they might constitute the biological target of HCQ treatment. For these reasons, we investigated whether DCs could affect the antimalarial responsiveness, and if DCs might be used as predictive factor of responsiveness to HCQ. In this retrospective cohort study, 65 patients diagnosed with PCA were grouped accordingly to their response to HCQ therapy. Skin biopsies had been taken before the treatment was started. Cell count was performed on immunohistochemistry by using characteristic monoclonal antibodies to specific subpopulations of DCs. In almost every second patient (47.7%), we observed remission of the disease during HCQ treatment. The number of plasmacytoid and myeloid DCs as well as Langerhans cells in lesional skin of HCQ responders was higher in comparison with HCQ nonresponders. Moreover, in a predictive model receiver operating characteristic (ROC curve) we showed that plasmacytoid DCs might be used as a predictive factor of responsiveness to HCQ. The results of this study are important as identifying biomarkers for responsiveness to a HCQ therapy will be helpful to individualize treatment and make it more effective.

Is hormone testing worthwhile in patients with female pattern hair loss?

Androgenetic alopecia (AGA) is the most common type of hair loss both in male and female patients. As regards its etiopathology, it is postulated that hair follicles grow sensitive to androgens in persons who are genetically predisposed to it. In the pathomechanism of the disease, hair follicles undergo miniaturization. AIM: The aim of the study was to evaluate the levels of selected hormones (sex hormones, adrenal and thyroid hormones), and the results of laboratory tests (iron metabolism) performed in a group of female patients with AGA in order to specify which of those tests should be taken during the diagnostic process in such patients. MATERIALS AND METHODS: Test results and types of therapies have been analyzed for a group of 106 adult female patients (of different age) with female pattern hair loss (FPHL) of different duration. Selected hormone parameters have been analyzed as well as iron metabolism, BMI ( body mass index), and signs of androgenization in the patients' histories (presence of menstrual disorders, hirsutism and acne). Additionally, their insulin levels were measured. RESULTS: The most common hormonal disorders in the study population involved increased concentrations of sex hormone binding globulin (SHBG) in 38.8%, decreased concentration of total testosterone in 25.4%, increased antibody titers against thyroid peroxidase (ATPO) in 17.3%, decreased concentrations of dihydroepiandrostendione (DHEAS) in 15.6%, and increased concentrations of insulin in 12.6%. Increased concentrations of free testosterone were only observed in 6.8 % of the study participants, and increased concentrations of cortisol were revealed in 6.7% of them. 40% of the patients complained about symptoms related to menstrual disorders, hirsutism and acne. Sex hormone concentrations did not correlate with the reported symptoms, and test results in that sub-group were not found to significantly differ from the rest of the patients who did not report signs of hyperandrogenism. CONCLUSIONS: In spite of the fact that nearly half of the patients reported symptoms which may be suggestive of hormonal disorders, no significant abnormalities were revealed in hormone tests.

Diagnostic accuracy of reflectance confocal microscopy for pigmented skin lesions presenting dermoscopic features of cutaneous melanoma.

INTRODUCTION: The incidence and mortality of melanoma are rising rapidly. Despite ongoing research and the introduction of new therapeutic methods, advanced melanoma is still considered incurable. Early detection and surgical excision of the tumor increases patients' survival. Since the diagnostic protocol includes surgical excision of all suspicious lesions, it is burdened with a high rate of unnecessary excisions that cause unwanted scarring. This is why the development of accurate diagnostic techniques is crucial. The most common diagnostic tool in early diagnosis of cutaneous melanoma is dermoscopy, though there are emerging new techniques, such as reflectance confocal microscopy and optical coherence tomography. AIM: To evaluate diagnostic accuracy of reflectance confocal microscopy as a secondary examination in melanocytic lesions previously diagnosed as melanomas by means of dermoscopy. MATERIAL AND METHODS: Forty-six melanocytic lesions presenting dermoscopic features of cutaneous malignant melanoma were examined by means of reflectance confocal microscopy. RESULTS: The RCM evaluation showed sensitivity at the level of 100% and specificity at 62%. CONCLUSIONS: It can be estimated that double evaluation of melanocytic lesions by dermoscopy and reflectance confocal microscopy may allow up to 62% of unnecessary excisions to be avoided.

Immune-related adverse events in a patient with eosinophilic enteritis treated with immune checkpoint inhibitors (anti-PD-1).

The use of immune checkpoint inhibitors (ICIs) in melanoma patients has significantly improved treatment outcomes. Unfortunately, ICI therapy is associated with specific immune-related adverse events (irAEs). There is limited data on the use of ICIs in patients with autoimmune or allergic diseases, because these patients have typically been excluded from clinical trials. Eosinophilic inflammatory bowel disease (primary eosinophilic gastrointestinal disorders) is a rare condition defined as eosinophilic infiltration in the wall of the gastrointestinal tract in the absence of other known causes of tissue eosinophilia. We present a case of a 51-year-old woman with eosinophilic enteritis who was treated with anti-PD-1 because of metastatic melanoma. The use of anti-PD-1 therapy in a metastatic melanoma patient with a positive history of eosinophilic enteritis resulted in the appearance of many immune-related complications (hypothyroidism, hepatitis, skin lesions, colitis). The patient discontinued anti-PD-1 treatment and glucocorticoid therapy was started. All AEs have resolved without any sequelae, and there are no symptoms of eosinophilic enteritis. Currently, the patient has no complaints, and has no clinical features of recurrence or dissemination of melanoma (April 2020); she remains under constant oncological supervision. The use of anti-PD-1 therapy in a patient with metastatic melanoma and a positive history of eosinophilic enteritis resulted in almost complete remission of melanoma but also the appearance of many immune-related complications, none of which were life-threatening. Patients with eosinophilic enteritis may be eligible for anti-PD-1 therapy; however, they should be closely monitored for the appearance of various irAEs when receiving this therapy.

Image analysis discloses differences in nuclear parameters between ERG+ and ERG- prostatic carcinomas.

Prostatic carcinoma (PC) is the most frequent urologic cancer and one of the most frequent cancers in males; it is a heterogeneous disease, in terms of molecular features, morphology and prognosis. About half of cases depends on TMPRSS2-ETS translocation which leads to a production of ERG transcription factor. ERG+ and ERG- cancers seem to differ in a number of features, which could lead to an altered nuclear structure; the aim of the study was to test this hypothesis. The material consisted of total 39 PC cases, representing ERG+ and ERG-, as well as Gleason pattern 3 and 4. Filtering by color deconvolution and automatic segmentation were used, and the properly detected nuclei were manually selected. From each case fifty nuclei were obtained; then geometric features and texture parameters were assessed. The analysis of the collected data showed differences both between ERG+/ERG- and Gleason pattern 3 and 4 cases in most of the features analyzed. Our results suggest that indeed the ERG status, thus likely TMPRSS2-ETS translocation, has an impact on morphology of nuclei in PC, and their differences are evident enough to be detectable by image analysis.

Bacillary Angiomatosis in Renal Transplant Recipient: A Case Report.

INTRODUCTION: Bacillary angiomatosis (BA) is a rare, opportunistic infectious disease caused by the aerobic Gram-negative bacilli Bartonella henselae or Bartonella quintana. The main reservoir for those microbes are cats. The disease mostly affects immunocompromised patients with human immunodeficiency virus infection, after organ transplantation, undergoing corticosteroid and methotrexate therapy or with oncological history. CASE REPORT: We represent the case of a 65-year-old man who reported to the Department of Dermatology with a high fever and numerous nodular skin lesions on the 5th month of kidney transplantation. At that time, his immunosuppressive therapy consisted of tacrolimus 6 mg/day, mycophenolate mofetil 2 g/day, and prednisone 5 mg/day. Laboratory tests revealed an increased leukocyte count and elevated values of acute-phase proteins, but blood cultures were negative. Skin biopsy was performed and BA was diagnosed. The patient was given oral doxycycline 100 mg twice a day. During antibiotic therapy, his body temperature normalized and skin lesions began to resolve. The patient continued the above treatment for the next 3 months with good tolerance, and no relapse occurred in 1 year. CONCLUSION: BA should be listed among possible opportunistic infections in organ transplant recipients.

Semi-Supervised Nests of Melanocytes Segmentation Method Using Convolutional Autoencoders.

In this research, we present a semi-supervised segmentation solution using convolutional autoencoders to solve the problem of segmentation tasks having a small number of ground-truth images. We evaluate the proposed deep network architecture for the detection of nests of nevus cells in histopathological images of skin specimens is an important step in dermatopathology. The diagnostic criteria based on the degree of uniformity and symmetry of border irregularities are particularly vital in dermatopathology, in order to distinguish between benign and malignant skin lesions. However, to the best of our knowledge, it is the first described method to segment the nests region. The novelty of our approach is not only the area of research, but, furthermore, we address a problem with a small ground-truth dataset. We propose an effective computer-vision based deep learning tool that can perform the nests segmentation based on an autoencoder architecture with two learning steps. Experimental results verified the effectiveness of the proposed approach and its ability to segment nests areas with Dice similarity coefficient 0.81, sensitivity 0.76, and specificity 0.94, which is a state-of-the-art result.

The level of stress and the assessment of selected clinical parameters in patients with androgenetic alopecia.

Androgenetic alopecia is the most common type of hair loss both in male as well as female patients. It is a type of non-cicatricial hair loss. Pathophysiology of the disease remains largely unknown. It is believed that the occurrence of FPHL (female pattern hair loss) is linked with cellular insensitivity to androgens. Human hair does not only represent beauty, health and youth, but it also has a significant impact on one's self-esteem. For many patients, hair loss is a stigmatizing experience, many of them complain about a lower quality of life, anxiety or even depression. AIM: Aim of the study was to evaluate the levels of selected clinical parameters, including exposure to stress and disease progression based on the Ludwig scale, and of the applied therapies in a group of female patients with androgenetic alopecia. MATERIALS AND METHODS: A group of 106 patients with androgenetic alopecia was analyzed with respect to their age, duration of disease, disease progression based on the Ludwig scale, family history of AGA, exposure to stress (with the level of stress subjectively assessed by the patients using a score of 1 to 10), and treatment modality. Comparison of the results will be carried out with the help of the Statistica software, using the Student's t-test or its non-parametric equivalent. RESULTS: Patients reported very high levels of stress exposure: 7 and 8 on a scale of 1 to 10. The type of treatment applied (local vs. systemic) was of no significance with respect to the alleviation of stress. Disease progression was not found to correlate with the level of stress. When analyzing disease progression, using the Ludwig classification scale, most of the patients met the criteria of type I-2 (24.74%). As regards the comparison of treatment modalities in the study group, a great majority of patients was treated with topical agents in the form of scalp massage liquids (80.00%), while 17.14% of the study population underwent systemic treatment. A small percentage of patients also resorted to esthetic medicine procedures (3.81%), and 22.86% of them used dietary supplements or OTC topical agents. CONCLUSIONS: High levels of stress exposure reported by patients most probably stemmed from the symptoms of the disease itself, as the study population was quite diverse in terms of their levels of professional activity and the type of profession performed.

In vivo Studies on Pharmacokinetics, Toxicity and Immunogenicity of Polyelectrolyte Nanocapsules Functionalized with Two Different Polymers: Poly-L-Glutamic Acid or PEG.

BACKGROUND: The functionalization of a nanoparticle surface with PEG (polyethylene glycol) is an approach most often used for extending nanomaterial circulation time, enhancing its delivery and retention in the target tissues, and decreasing systemic toxicity of nanocarriers and their cargos. However, because PEGylated nanomedicines were reported to induce immune response including production of anti-PEG antibodies, activation of the complement system as well as hypersensitivity reactions, hydrophilic polymers other than PEG are gaining interest as its replacement in nanomaterial functionalization. Here, we present the results of in vivo evaluation of polyelectrolyte nanocapsules with biodegradable, polyelectrolyte multilayer shells consisting of poly-l-lysine (PLL) and poly-l-glutamic (PGA) acid as a potential drug delivery system. We compared the effects of nanocapsules functionalized with two different "stealth" polymers as the external layer of tested nanocapsules was composed of PGA (PGA-terminated nanocapsules, NC-PGA) or the copolymer of poly-l-lysine and polyethylene glycol (PEG-terminated nanocapsules, NC-PEG). METHODS: Nanocapsules pharmacokinetics, biodistribution and routes of eliminations were analysed postmortem by fluorescence intensity measurement. Toxicity of intravenously injected nanocapsules was evaluated with analyses of blood morphology and biochemistry and by histological tissue analysis. DNA integrity was determined by comet assay, cytokine profiling was performed using flow cytometer and detection of antibodies specific to PEG was performed by ELISA assay. RESULTS: We found that NC-PGA and NC-PEG had similar pharmacokinetic and biodistribution profiles and both were eliminated by hepatobiliary and renal clearance. Biochemical and histopathological evaluation of long-term toxicity performed after a single as well as repeated intravenous injections of nanomaterials demonstrated that neither NC-PGA nor NC-PEG had any acute or chronic hemato-, hepato- or nephrotoxic effects. In contrast to NC-PGA, repeated administration of NC-PEG resulted in prolonged increased serum levels of a number of cytokines. CONCLUSION: Our results indicate that NC-PEG may cause undesirable activation of the immune system. Therefore, PGA compares favorably with PEG in equipping nanomaterials with stealth properties. Our research points to the importance of a thorough assessment of the potential influence of nanomaterials on the immune system.

Analysis of toxicity and anticancer activity of micelles of sodium alginate-curcumin.

BACKGROUND: Curcumin is a natural polyphenol with anti-inflammatory, chemopreventive and anticancer activity. However, its high hydrophobicity and poor bioavailability limit its medical application. The development of nanocarriers for curcumin delivery is an attractive approach to overcome its low bioavailability and fast metabolism in the liver. We synthesized a blood compatible alginate-curcumin conjugate, AA-Cur, which formed colloidally stable micelles of approximately 200 nm and, as previously shown, exerted strong cytotoxicity against mouse cancer cell lines. Here we analyze in vivo toxicity and antitumor activity of AA-Cur in two different mouse tumor models. METHOD: Potential toxicity of intravenously injected AA-Cur was evaluated by: i) analyses of blood parameters (morphology and biochemistry), ii) histology, iii) DNA integrity (comet assay), and iv) cytokine profiling (flow cytometry). Antitumor activity of AA-Cur was evaluated by measuring the growth of subcutaneously inoculated colon MC38-CEA- or orthotopically injected breast 4T1 tumor cells in control mice vs mice treated with AA-Cur. RESULTS: Injections of four doses of AA-Cur did not reveal any toxicity of the conjugate, thus indicating the safety of its use. AA-Cur elicited moderate anti-tumor activity toward colon MC38-CEA or breast 4T1 carcinomas. CONCLUSION: The tested conjugate of alginate and curcumin, AA-Cur, is non-toxic and safe, but exhibits limited anticancer activity.