Retraction notice to "The therapeutic potential of human adipose-derived mesenchymal stem cells producing CXCL10 in a mouse melanoma lung metastasis model" [Cancer Lett. 419 (2018) 30-39].

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor. After publication, the Editors were contacted by a concerned reader regarding alleged image duplication. These allegations are in regard to Fig. 3a being duplicated from a previously published paper in the journal Stem Cells (Stem Cells. 2008 Sep;26 (9):2332-8. doi: 10.1634/stemcells.2008-0084) and Fig. 8a being duplicated from a previously published paper in the journal Molecular Cancer (Mol Cancer 13, 255 (2014). https://doi.org/10.1186/1476-4598-13-255). After a thorough investigation by the editorial team, the Editors determined that there are multiple identical details between Fig. 5A (Cancer Letters) and Fig. 3A (Stem Cells) and the authors did not produce satisfactory evidence that the published images in Cancer Letters were original. Due to this, the Editor does not have confidence in the results and conclusions presented and has made the decision to retract.

Computational pathology identifies immune-mediated collagen disruption to predict clinical outcomes in gynecologic malignancies.

BACKGROUND: The role of immune cells in collagen degradation within the tumor microenvironment (TME) is unclear. Immune cells, particularly tumor-infiltrating lymphocytes (TILs), are known to alter the extracellular matrix, affecting cancer progression and patient survival. However, the quantitative evaluation of the immune modulatory impact on collagen architecture within the TME remains limited. METHODS: We introduce CollaTIL, a computational pathology method that quantitatively characterizes the immune-collagen relationship within the TME of gynecologic cancers, including high-grade serous ovarian (HGSOC), cervical squamous cell carcinoma (CSCC), and endometrial carcinomas. CollaTIL aims to investigate immune modulatory impact on collagen architecture within the TME, aiming to uncover the interplay between the immune system and tumor progression. RESULTS: We observe that an increased immune infiltrate is associated with chaotic collagen architecture and higher entropy, while immune sparse TME exhibits ordered collagen and lower entropy. Importantly, CollaTIL-associated features that stratify disease risk are linked with gene signatures corresponding to TCA-Cycle in CSCC, and amino acid metabolism, and macrophages in HGSOC. CONCLUSIONS: CollaTIL uncovers a relationship between immune infiltration and collagen structure in the TME of gynecologic cancers. Integrating CollaTIL with genomic analysis offers promising opportunities for future therapeutic strategies and enhanced prognostic assessments in gynecologic oncology.

The role of cells that are part of our immune system in altering the structure of the protein collagen within cancers is not fully understood, particularly within cancers that affect women such as ovarian, cervical and uterine cancers. Here, we developed a computer-based method called CollaTIL to explore how immune cells influence collagen in these tumors and affect their growth. We found that a higher presence of immune cells leads to less organized collagen in the tumor. Conversely, when there are fewer immune cells, the collagen tends to be more structured. Additionally, CollaTIL identifies patterns that predict patient outcomes in these cancers. These findings not only enhance our understanding of tumor biology but also may be useful in helping clinicians to predict which patients are at risk of their disease progressing.

Platelet to lymphocyte and neutrophil to lymphocyte ratio in the first trimester of pregnancy, are they useful for predicting spontaneous miscarriage? A case-control study.

Background: In 15% of all clinical pregnancies, a miscarriage can occur, but the exact cause of this phenomenon is not fully understood. However, it is believed that a faulty placenta, which triggers an inflammatory response in the mother's body, may be one of the causes. Medical literature has increasingly focused on 2 indicators of inflammation, the platelet-lymphocyte ratio (PLR) and neutrophil-lymphocyte ratio (NLR). Despite this, there has yet to be a study conducted that examines the rates of PLR and NLR in cases of miscarriage. Objective: This study aims to determine whether there is an increase in complete blood count inflammatory parameters such as NLR and PLR in women who experience miscarriages. Materials and Methods: This retrospective case-control study was conducted from March 2021 to March 2022, across 3 academic hospitals in Tehran, Iran. A total of 240 participants were enrolled comprising individuals with either miscarriages or normal pregnancies (n = 120/each). Data were collected from the medical records of participants aged between 18-42 yr old, with gestational age ranging from 6-13 wk. The demographic information, including age, body mass index, parity, history of abortion, number of abortions, number of living children, hematocrit and hemoglobin levels, platelet distribution width (PDW), PLR, NLR, mean platelet volume, and platelet were extracted from their records. The gestational age was also recorded. Results: A total of 240 participants were recruited for the study. PDW, NLR, PLR, and lymphocyte values were higher in the miscarriage group compared to the healthy normal pregnant women (p < 0.001). Mean platelet volumes were found to be lower in the miscarriage group compared to the healthy normal pregnant women (p < 0.001). Conclusion: Although, no statistically significant difference was observed in the hemoglobin, hematocrit, platelets, and neutrophils in these 2 groups of pregnant women. The higher inflammatory markers including PDW, NLR, and PLR could potentially aid in the speculation of defective placentation as a contributing factor to the development of miscarriage. Measurement of these markers may be useful to predict pregnancy leading to miscarriage.

Computational pathology improves risk stratification of a multi-gene assay for early stage ER+ breast cancer.

Prognostic markers currently utilized in clinical practice for estrogen receptor-positive (ER+) and lymph node-negative (LN-) invasive breast cancer (IBC) patients include the Nottingham grading system and Oncotype Dx (ODx). However, these biomarkers are not always optimal and remain subject to inter-/intra-observer variability and high cost. In this study, we evaluated the association between computationally derived image features from H&E images and disease-free survival (DFS) in ER+ and LN- IBC. H&E images from a total of n = 321 patients with ER+ and LN- IBC from three cohorts were employed for this study (Training set: D1 (n = 116), Validation sets: D2 (n = 121) and D3 (n = 84)). A total of 343 features relating to nuclear morphology, mitotic activity, and tubule formation were computationally extracted from each slide image. A Cox regression model (IbRiS) was trained to identify significant predictors of DFS and predict a high/low-risk category using D1 and was validated on independent testing sets D2 and D3 as well as within each ODx risk category. IbRiS was significantly prognostic of DFS with a hazard ratio (HR) of 2.33 (95% confidence interval (95% CI) = 1.02-5.32, p = 0.045) on D2 and a HR of 2.94 (95% CI = 1.18-7.35, p = 0.0208) on D3. In addition, IbRiS yielded significant risk stratification within high ODx risk categories (D1 + D2: HR = 10.35, 95% CI = 1.20-89.18, p = 0.0106; D1: p = 0.0238; D2: p = 0.0389), potentially providing more granular risk stratification than offered by ODx alone.

Phaeohyphomycosis caused by Neoscytalidiumdimidiatum in a COVID-19 patient.

BACKGROUND: Neoscytalidiumdimidiatum is an opportunistic dematiaceous fungus belonging to the class Dothideomycetes. CASE REPORT: We report a case of N. dimidiatum cerebral phaeohyphomycosis post COVID-19 infection in a 32-year-old male from Iran. The causative agent was identified by cytopathology, routine mycological methods, and DNA sequencing of the internal transcribed spacer (ITS) region of rDNA. Apart from COVID-19 complications and the corticosteroid therapy, no underlying condition was diagnosed. The symptoms suggesting the fungal infection were shown two weeks after being discharged from COVID-19 hospital stay. Magnetic resonance of the brain showed a multi-focal central nervous system infection. The delayed identification of the fungus and, thus, a late starting of the antifungal treatment with amphotericin B, might have affected the patient outcome as he finally died. CONCLUSIONS: Considering the rare incidence of N. dimidiatum infections, this case should aware us about them, leading to a timely antifungal management.

Prediction of Intraperitoneal Adhesions in Repeated Cesarean Section Using Sliding Sign, Striae Gravidarum, and Cesarean Scar.

Background: Intraabdominal adhesions are associated with an increase in complications during cesarean section because of recurrent cesarean sections. This is why the possibility of predicting adhesions is important. In this study, the diagnostic value of depressed scar, severe striae gravidarum, and negative sliding sign, and their combinations were evaluated for predicting intraabdominal adhesions of cesarean candidates. Methods: This prospective descriptive study was performed during 2019-2020 on 123 pregnant women referred to Ayatollah Taleghani university hospital with a gestational age of ≥36 weeks 0 days who were candidates for cesarean section because of a previous cesarean section. In each patient, the presence of a depressed scar, a severe striae gravidarum, the absence of a sliding sign, and the presence and severity of adhesions during the operation were examined. Sensitivity and specificity, and positive and negative predictive values of each of the 3 indicators and their combinations were calculated. Results: The frequency distribution of severe adhesion in these individuals was 16.27%. The highest sensitivity was related to depressed scar and negative sliding sign (65%). The highest specificity was related to the negative sliding sign and its combinations (97%-99%). The highest positive predictive value was related to negative sign sliding and its combinations (81%-92%). The negative predictive values of depressed scar, negative sliding sign, and severe striae gravidarum, and even their combinations were almost the same and approximately between 89% and 93%. Conclusion: To predict the presence of adhesions in a cesarean candidate because of a previous cesarean section, you should first examine the striae gravidarum and scar. In the absence of a depressed scar and severe striae gravidarum, there is a 90% chance of no adhesions. According to this study, if both signs are present, it is recommended to check the sliding sign to obtain a more accurate estimate.

Improving the Diagnosis of Skin Biopsies Using Tissue Segmentation.

Invasive melanoma, a common type of skin cancer, is considered one of the deadliest. Pathologists routinely evaluate melanocytic lesions to determine the amount of atypia, and if the lesion represents an invasive melanoma, its stage. However, due to the complicated nature of these assessments, inter- and intra-observer variability among pathologists in their interpretation are very common. Machine-learning techniques have shown impressive and robust performance on various tasks including healthcare. In this work, we study the potential of including semantic segmentation of clinically important tissue structure in improving the diagnosis of skin biopsy images. Our experimental results show a 6% improvement in F-score when using whole slide images along with epidermal nests and cancerous dermal nest segmentation masks compared to using whole-slide images alone in training and testing the diagnosis pipeline.

Isonicotinic acid hydrazide (INH) versus extra-amniotic saline infusion (EASI) for cervical ripening at term: a randomised controlled trial.

The purpose of this trial was to compare extra-amniotic saline infusion (EASI) and intravaginal isoniazid (INH) for cervical ripening. This randomised clinical trial included 150 pregnant women who were undergoing induction of labour and who required pre-induction cervical ripening. Patients were randomly assigned to receive EASI or intravaginal INH. Bishop's score at the beginning of the study and before oxytocin infusion was not significantly different between INH and EASI groups. However, the time from first intervention to the beginning of the induction and also to the beginning of the active phase were significantly shorter in EASI group (p value ≤.001). Moreover, INH did not influence the labour process after the beginning of the active phase of labour. In conclusion, INH could be used for cervical ripening especially in the outpatient setting; however, it is a slower ripening agent compared to EASI.Impact StatementWhat is already known on this subject? To date there has been only one study about the safety and effectiveness of isoniazid (INH) in cervical ripening at term pregnancy which has compared INH with misoprostol.What do the results of this study add? The results of this study showed that vaginal INH is an effective agent for cervical ripening at term but in comparison to extra-amniotic saline infusion (EASI) it takes a longer time.What are the implications of these findings for clinical practice and/or further research? INH can be used in outpatient settings for cervical ripening at term pregnancy which makes it convenient for patient and cost effective for both patient and health system. Further studies are needed to discover the clinical efficacy of INH in comparison to other ripening methods and also the best dosage of INH for cervical ripening.

Comparative evaluation of normal saline, 1/3-2/3, and ringer's lactate infusion on labour outcome, PH, bilirubin, and glucose level of the umbilical cord blood in nulliparous women with labour induction: a randomised clinical trial.

This study aimed to compare the effects of infusion of normal saline, 1/3-2/3, and Ringer's lactate fluids on labour outcome, pH, bilirubin, and glucose level of umbilical cord blood. In this randomised clinical trial, 450 nulliparous women with Bishop score ˂5 and indication of pregnancy termination were randomly divided into three groups to receive normal saline, 1/3-2/3, or Ringer's lactate infusion at a rate of 125 mL/h for hydration, upon starting induction of labour. Results of this study indicated that the incidence of hypoglycaemia (p = .19), hyper bilirubinemia (p = .87) and acidosis (p = .10) was similar in neonates of the three groups. Also, there were no statistically significant differences between the three groups with regard to the duration of labour; glucose, bilirubin and pH level of cord blood; and mode of delivery. It can be concluded that infusion of Ringer's lactate, normal saline or 1/3-2/3 fluid during labour is not associated with different maternal or foetal/neonatal outcomes, and none of the fluids has superiority to the others.Impact statementWhat is already known on this subject? Several studies have been conducted on the association between type and volume of infused fluid on labour duration and neonatal outcomes. However, there has been some controversy.What do the results of this study add? This is the first study that has investigated the association between infusion of Ringer's lactate, normal saline or 1/3-2/3 fluid during labour with labour outcome and pH, bilirubin, and glucose level of the umbilical cord blood and results showed that these fluids have no effect on maternal or foetal/neonatal outcomes and also none of these fluids has superiority to the others.What are the implications of these findings for clinical practice and/or further research? Due to contradictory results of previous studies, further research with greater sample sizes and different fluids type and volumes may be needed to examine the association between infusion of fluids and neonatal and labour outcomes more precisely.

Segmenting Skin Biopsy Images with Coarse and Sparse Annotations using U-Net.

The number of melanoma diagnoses has increased dramatically over the past three decades, outpacing almost all other cancers. Nearly 1 in 4 skin biopsies is of melanocytic lesions, highlighting the clinical and public health importance of correct diagnosis. Deep learning image analysis methods may improve and complement current diagnostic and prognostic capabilities. The histologic evaluation of melanocytic lesions, including melanoma and its precursors, involves determining whether the melanocytic population involves the epidermis, dermis, or both. Semantic segmentation of clinically important structures in skin biopsies is a crucial step towards an accurate diagnosis. While training a segmentation model requires ground-truth labels, annotation of large images is a labor-intensive task. This issue becomes especially pronounced in a medical image dataset in which expert annotation is the gold standard. In this paper, we propose a two-stage segmentation pipeline using coarse and sparse annotations on a small region of the whole slide image as the training set. Segmentation results on whole slide images show promising performance for the proposed pipeline.

Computational image features of immune architecture is associated with clinical benefit and survival in gynecological cancers across treatment modalities.

BACKGROUND: We present a computational approach (ArcTIL) for quantitative characterization of the architecture of tumor-infiltrating lymphocytes (TILs) and their interplay with cancer cells from digitized H&E-stained histology whole slide images and evaluate its prognostic role in three different gynecological cancer (GC) types and across three different treatment types (platinum, radiation and immunotherapy). METHODS: In this retrospective study, we included 926 patients with GC diagnosed with ovarian cancer (OC), cervical cancer, and endometrial cancer with available digitized diagnostic histology slides and survival outcome information. ArcTIL features quantifying architecture and spatial interplay between immune cells and the rest of nucleated cells (mostly comprised cancer cells) were extracted from the cell cluster graphs of nuclei within the tumor epithelial nests, surrounding stroma and invasive tumor front compartments on H&E-stained slides. A Cox proportional hazards model, incorporating ArcTIL features was fit on the OC training cohort (N=51), yielding an ArcTIL signature. A unique threshold learned from the training set stratified the patients into a low and high-risk group. RESULTS: The seven feature ArcTIL classifier was found to significantly correlate with overall survival in chemotherapy and radiotherapy-treated validation cohorts and progression-free survival in an immunotherapy-treated validation cohort. ArcTIL features relating to increased density of TILs in the epithelium and invasive tumor front were found to be associated with better survival outcomes when compared with those patients with an increased TIL density in the stroma. A statistically significant association was found between the ArcTIL signature and signaling pathways for blood vessel morphogenesis, vasculature development, regulation of cell differentiation, cell-substrate adhesion, biological adhesion, regulation of vasculature development, and angiogenesis. CONCLUSIONS: This study reveals that computationally-derived features from the spatial architecture of TILs and tumor cells are prognostic in GCs treated with chemotherapy, radiotherapy, and checkpoint blockade and are closely associated with central biological processes that impact tumor progression. These findings could aid in identifying therapy-refractory patients and further enable personalized treatment decision-making.

An Imaging Biomarker of Tumor-Infiltrating Lymphocytes to Risk-Stratify Patients With HPV-Associated Oropharyngeal Cancer.

BACKGROUND: Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) has excellent control rates compared to nonvirally associated OPSCC. Multiple trials are actively testing whether de-escalation of treatment intensity for these patients can maintain oncologic equipoise while reducing treatment-related toxicity. We have developed OP-TIL, a biomarker that characterizes the spatial interplay between tumor-infiltrating lymphocytes (TILs) and surrounding cells in histology images. Herein, we sought to test whether OP-TIL can segregate stage I HPV-associated OPSCC patients into low-risk and high-risk groups and aid in patient selection for de-escalation clinical trials. METHODS: Association between OP-TIL and patient outcome was explored on whole slide hematoxylin and eosin images from 439 stage I HPV-associated OPSCC patients across 6 institutional cohorts. One institutional cohort (n = 94) was used to identify the most prognostic features and train a Cox regression model to predict risk of recurrence and death. Survival analysis was used to validate the algorithm as a biomarker of recurrence or death in the remaining 5 cohorts (n = 345). All statistical tests were 2-sided. RESULTS: OP-TIL separated stage I HPV-associated OPSCC patients with 30 or less pack-year smoking history into low-risk (2-year disease-free survival [DFS] = 94.2%; 5-year DFS = 88.4%) and high-risk (2-year DFS = 82.5%; 5-year DFS = 74.2%) groups (hazard ratio = 2.56, 95% confidence interval = 1.52 to 4.32; P < .001), even after adjusting for age, smoking status, T and N classification, and treatment modality on multivariate analysis for DFS (hazard ratio = 2.27, 95% confidence interval = 1.32 to 3.94; P = .003). CONCLUSIONS: OP-TIL can identify stage I HPV-associated OPSCC patients likely to be poor candidates for treatment de-escalation. Following validation on previously completed multi-institutional clinical trials, OP-TIL has the potential to be a biomarker, beyond clinical stage and HPV status, that can be used clinically to optimize patient selection for de-escalation.

The Effect of Various Pre-Cesarean Fasting Times on Maternal and Neonatal Outcomes.

Background: Although it is currently recommended that patients avoid solid food for 6-8 h and liquid for 2 h before cesarean section, longer restrictions still apply in many centers. Since studies on the duration of fasting before cesarean section is scarce, we aimed to investigate the effect of different fasting times before cesarean section on maternal and neonatal complications. Materials and methods: This descriptive study was performed on 405 candidates for cesarean section. These women were divided into five groups due to the length of time they did not consume clear liquid and solid food. Then, maternal and neonatal outcomes were compared using Kruskal-Wallis and Chi-square tests. Results: The rate of nausea during surgery was lower in the groups who ate solid food between 2 and 8 h and clear liquid <2 h before surgery (P = 0.04). Also, abdominal distension in the first 6 h after surgery in the group that did not eat solid food for <6-8 h and clear liquid for <2 h was more than in the other groups (P < 0.05). The prevalence of hypoglycemia was significantly lower in women who ate solid food for <6 h and drank clear liquid for <2 h (P < 0.05). Conclusion: Prolonged fasting time before cesarean section not only reduce complications but also may have undesirable consequences. The results of this study showed that it is better to use less strict measures in patients who are candidates for cesarean section and in patients with labor pains who are likely to have a cesarean section.

Skin Melanoma Detection in Microscopic Images Using HMM-Based Asymmetric Analysis and Expectation Maximization.

Melanoma is one of the deadliest types of skin cancer with increasing incidence. The most definitive diagnosis method is the histopathological examination of the tissue sample. In this paper, a melanoma detection algorithm is proposed based on decision-level fusion and a Hidden Markov Model (HMM), whose parameters are optimized using Expectation Maximization (EM) and asymmetric analysis. The texture heterogeneity of the samples is determined using asymmetric analysis. A fusion-based HMM classifier trained using EM is introduced. For this purpose, a novel texture feature is extracted based on two local binary patterns, namely local difference pattern (LDP) and statistical histogram features of the microscopic image. Extensive experiments demonstrate that the proposed melanoma detection algorithm yields a total error of less than 0.04%.

Investigation of microRNA-10b values for the discrimination of metastasis due to melanoma.

BACKGROUND: Melanoma is one of the most invasive cutaneous cancers with characteristics such as rapid progression and distant metastasis. The early diagnosis and staging of melanoma can help better manage the patients. The current study is aimed to assess the values of microRNA-10b (miRNA-10b) in the discrimination of metastatic melanomas. MATERIALS AND METHODS: The current cross-sectional study has been conducted on forty patients diagnosed with melanoma since 2011. Cell culture of melanoma cell lines derived from the cancerous tissue, including WM115, BLM, K1735, WM793, and A375M, was cultured. In order to assess miRNA-10b levels, the real-time polymerase chain reaction was utilized. The absence (n = 20)/presence (n = 20) of metastasis was diagnosed with chest computed tomography or chest X-ray. The values of miRNA-10b for the discrimination of metastasis incidence were assessed. RESULTS: The demographic characteristics, including age and gender of the metastatic and nonmetastatic patients, were similar (P > 0.05). The specimen cultures were positive for miRNA-10b in 14 (35%) of the metastatic cases versus 4 (20%) of the nonmetastatic ones (P = 0.004). The quantitative analysis of miR-2b revealed significantly higher levels in metastatic cases (-1.59 ± 1.13 in metastatic vs. -0.16 ± 0.67 in nonmetastatic cases; P = 0.001). The measured area under the curve for the value of miRNA-10b was 0.923 (P < 0.001; 95% confidence interval: 0.811-1) with sensitivity and specificity of 100% and 94.4%. CONCLUSION: Based on this study, metastatic melanoma was associated with elevated levels of miRNA-10b. This marker had the sensitivity and specificity of 100% and 94.4% for the discrimination of metastatic melanoma from nonmetastatic ones.

In Vitro and In Vivo Evaluation of Novel DTX-Loaded Multifunctional Heparin-Based Polymeric Micelles Targeting Folate Receptors and Endosomes.

BACKGROUND: The development of biocompatible tumor-targeting delivery systems for anticancer agents is essential for efficacious cancer chemotherapy. Nanoparticles, as drug delivery cargoes for cancer therapy, are rapidly improving to overcome the limitations of conventional chemotherapeutic agents. Heparin-modified nanoparticles are currently being considered as one of the favorable carriers for the delivery of chemotherapeutics to cancer tissues. OBJECTIVE: This study was aimed at evaluating the in vitro and in vivo antitumor activity of a novel targeted, pH-sensitive, heparin-based polymeric micelle loaded with the poorly water-soluble anticancer drug, docetaxel (DTX). The micelles could overcome the limited water solubility, non-specific distribution, and insufficient drug concentration in tumor tissues. METHODS: DTX-loaded folate targeted micelles were prepared and evaluated for physicochemical properties, drug release, in vitro cellular uptake and cytotoxicity in folate receptor-positive and folate receptor-negative cells. Furthermore, the antitumor activity of DTX-loaded micelles was evaluated in the tumor-bearing mice. Some related patents were also studied in this research. RESULTS: The heparin-based targeted micelles exhibited higher in vitro cellular uptake and cytotoxicity against folate receptor over-expressed cells due to the specific receptor-mediated endocytosis. DTX-loaded micelles displayed greater antitumor activity, higher anti-angiogenesis effects, and lower systemic toxicity compared with free DTX in a tumor-induced mice model as confirmed by tumor growth monitoring, immunohistochemical evaluation, and body weight shift. DTX-loaded targeting micelles demonstrated no considerable toxicity on major organs of tumor-bearing mice compared with free DTX. CONCLUSION: Our results indicated that DTX-loaded multifunctional heparin-based micelles with desirable antitumor activity and low toxicity possess great potential as a targeted drug delivery system in the treatment of cancer.

Nanomicellar-curcumin exerts its therapeutic effects via affecting angiogenesis, apoptosis, and T cells in a mouse model of melanoma lung metastasis.

BACKGROUND: Curcumin is a natural phytochemical polyphenol with significant anti-cancer effects and negligible side effects. In this study, the therapeutic capacity of nanomicellar-curcumin for treating lung metastasis was evaluated in an immunocompetent mouse model of metastatic melanoma. MARTIALS AND METHODS: Two doses of nanomicellar-curcumin (i.e. 10 and 20 µM) were used to induce cytotoxicity in 3 melanoma cell lines. A total of 60 mice were allocated to 20 mice in each of three groups (10 for survival and 10 for assays). Groups were no treatment control, PBS control, nanomicellar-curcumin 20 mg/kg IP 4 times a week, for three weeks). Immunohistochemistry, TUNEL assay, and Western blots were used on lung samples. RESULTS: Nanomicellar-curcumin inhibited the in vitro growth of B16 F10 melanoma cells at 20 µM over 72 h. In vivo, 20 mg/kg nanomicellar-curcumin injected IP, delayed tumor cell growth and significantly extended mouse survival rate. Tumor infiltration of regulatory T cells and angiogenesis were reduced, while IFN-γ and CXCL10 were increased. CONCLUSION: Nanomicellar-curcumin can inhibit lung metastasis and growing melanoma via activation of apoptosis, activated T cells and inhibition of angiogenesis, tumor growth and regulatory T cells.

The effect of Punica granatum L. flower extract on post-surgical peritoneal adhesions in a rat model.

OBJECTIVE: Peritoneal adhesions may develop after every abdominopelvic surgery. Many agents and technical modifications have been investigated to minimize adhesions. Punica granatum (pomegranate) flower has some anti-inflammatory and antioxidative effects that would reduce the formation of peritoneal adhesions. In the present study, the effects of different doses of oral Punica granatum flower extract on postoperative peritoneal adhesions were evaluated in a rat model. STUDY DESIGN: Thirty-two female Wistar rats were divided into four groups: one control group (CG) and three experimental groups, treated with 100 (EG100), 200 (EG200), and 400 (EG400) mg/kg/day Punica granatum extract orally for eight days. Induction of peritoneal adhesions was done in all groups using the same method. Two weeks after the first surgery, all rats re-operated and adhesions were evaluated via both macroscopic and microscopic changes. RESULTS: We observed that rats in the control group had statistically higher adhesion area and more severe adhesions when compared to all experimental groups. Besides, those in the EG-400 group had a significantly lower rate of foreign body reaction in serosal layer when compared to the other three study groups. Other microscopic findings were comparable between the four groups. CONCLUSION: Administration of the oral Punica granatum flower extract was associated with a decreased quantity and quality of the adhesions in the animal model of rat in this study. This therapy might be an effective and safe strategy to reduce intraperitoneal adhesion after abdominal surgeries in animal models.

Association of ACE I/D and AGTR1 A1166C Gene Polymorphisms and Risk of Uterine Leiomyoma: A Case-Control Study.

Objective: Uterine leiomyoma (UL) can be considered as the most common benign gynecological tumors of the smooth muscle cells in the myometrium. They are likely to be associated with infertility and recurrent abortion as well as obstructed labor and post-partum hemorrhage. Moreover, altered vascular-related genes can be linked to developing leiomyoma. Polymorphisms of the angiotensin-converting enzyme (ACE) gene are associated with some vascular diseases. The present study was carried out to investigate the association of ACE I/D and AGTR1 A1166C gene polymorphisms and the risk of uterine leiomyoma in a sample of Iranian population. Methods: The study was carried out on a total of 413 women divided into 202 patients with diagnosed uterine leiomyomas and a control group of 211. Genotyping was performed using the PCR or PCR-RFLP methods. Results: The ID and DD genotypes of ACE I/D polymorphism were associated with 2 and 2.9 fold higher risk of UL compared to II genotype (OR, 2 [95% CI, 1.3 to 3.2]; P = 0.004 and OR, 2.9 [95% CI, 1.6 to 5]; P = 0.0002). The frequencies of ACE D alleles were 53.7% in women with UL and 40.3% in controls, which were observed to be statistically different (P < 0.0001). The alleles and genotypes of AGTR1 A1166C polymorphism were not different between UL and control women (P=0.9). Conclusion: The ACE ID and DD genotypes were associated with a higher risk of UL. No relationship was found between AGTR1 A1166C polymorphism and UL.

Cell Density Counts of the Intestinal Intraepithelial Lymphocytes in the Celiac Patients.

BACKGROUND: Increased number of intestinal intraepithelial lymphocytes (IELs) is a key histological finding in the diagnosis of celiac disease (CD); however, the number of IELs in celiac patients and healthy subjects may vary from one region to another. Additionally, there are some seronegative celiac patients with a borderline histology. OBJECTIVE: To determine the number of the CD3+ and CD8+ IELs T-cells in the celiac patients and healthy subjects (controls) in Isfahan. METHODS: The duodenal biopsies were obtained from the celiac patients (n=15) and the controls (n=19). The total number of IELs/100 epithelial cells (ECs) were counted using the hematoxylin-eosin (H&E) staining method, and that of CD3+ and CD8+ IELs/100 ECs were counted using the immunohistochemistry (IHC) staining method. RESULTS: This study defined the upper normal limit for each variable as mean + 2SD. Accordingly, the upper normal limits of the total IELs, CD3+ IELs, and CD8+ IELs/100 ECs were calculated as 37 (95% confidence intervals, CI: 33-41), 22 (95% CI: 19-25) and 12 (95% CI: 10-14), respectively. In 3 clinically CD diagnoses, the total IELs counts/100 ECs were below the upper normal limit, and the histopathological and serologic assays were negative. Nevertheless, the CD8+ IELs T-cells counts/100 ECs showed borderline values. Interestingly, these patients responded to a gluten-free diet (GFD). CONCLUSIONS: The study findings suggest that in the clinically diagnosed celiac disease, IELs count/100 ECs below the upper normal limit as well as negative histopathological and serologic assays and the cell density counts of the CD8+ IELs T-cells/100 ECs could be a useful parameter in CD diagnosis and make a decision to put them on a GFD.