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Background: Cancer is a multistep process that develops very rapidly after its onset. Previous studies have confirmed antitumor effects of curcumin (1,7-bis (4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione diferuloylmethane) that can potentially prevent colon cancer development with low side-effects. Different methods have been performed to increase the efficiency and effectiveness of curcumin among which dendrosome, a nanoparticle created by Sarbolouki et al. was used in this study. The present study was undertaken to evaluate the effects of dendrosomal curcumin on rat colon cancer. Methods: In this study which was performed in Cancer Research Center of Tehran University of Medical Sciences in 2010 year, forty rats were equally divided into control, curcumin and curcumin-dendrosome groups. Animals received azoxymethane (15 mg/kg s.c.), a carcinogen, once a week for two weeks. Curcumin (0.2%) and curcumin-dendrosome were administered to the respective animals 2 weeks before the first and 14 weeks after the last azoxymethane injections. Eventually, colorectal specimens from tumoral and adjacent non-tumoral mucosal tissues were fixed in 10% formaldehyde, and passaged and embedded in paraffin. Histopathological and immunohistochemical studies were performed on the specimens. Results: The mean number of lesions, nuclear/cytoplasmic ratio, epithelial stratification, loss of nuclear polarity, goblet depletion, structural abnormality and beta-catenin expression were higher in the control group compared to curcumin and curcumin-dendrosome groups. These parameters had significantly decreased in the dendrosomal curcumin group (P

This paper introduces a novel adaptive nonsingular fast terminal sliding mode approach that benefits from an interval type-2 fuzzy logic estimator and a gain for control and synchronization of chaotic systems in the presence of uncertainty. The nonsingular fast terminal sliding mode controller is developed to increase the convergence rate and remove the singularity problem of the system. Using the proposed method, the finite-time convergence has been ensured. To eliminate the chattering phenomenon in the conventional sliding mode controller, the discontinuous sign function is estimated using an interval type-2 fuzzy inference system (FIS) based on the center of sets type reduction followed by defuzzification. By adding the proportionate gain to the interval type-2 FIS, the robustness and speed of the controller system is enhanced. An appropriate Lyapunov function is utilized to ensure the closed-loop stability of the control system. The performance of the controller is evaluated for a nonlinear time-varying second-order magnetic space-craft chaotic system with different initial conditions in the presence of uncertainty. The simulation results show the efficacy of the proposed approach for the tracking control problems. The time and frequency domain analysis of the control signal demonstrates that the chattering phenomenon is successfully diminished. [ABSTRACT FROM AUTHOR]

Abstract Background Management of endometrial precancerous lesions has been of much debate due to inconsistencies in their classification, natural history and histologic diagnosis. Endometrial hyperplasia constitutes a wide range of histomorphologic features associated with high intra and interobserver diagnostic variability. Although traditional microscopic diagnosis is by far the most applicable method and the gold standard for histomorphologic diagnosis, digitized image analysis has been used as a powerful adjunct to maximize the histologic data retrieval and to add some detailed objective criteria for correct diagnosis in difficult cases. Methods A series of 100 endometrial curettage specimens with diagnosis of endometrial hyperplasia or well differentiated adenocarcinoma were blindly reviewed by 5 pathologists; their intra and interobserver reproducibility determined and further compared to the objective morphometric data i.e. D-score and volume percent of stroma (VPS). Results The results were assessed using the weighted kappa statistics. Mean intraobserver kappa value was 0.8690 (99.44% agreement). Mean interobserver kappa values by diagnostic category were: simple hyperplasia without atypia: 0.7441; complex hyperplasia without atypia: 0.3379; atypical hyperplasia: 0.3473, and well-differentiated endometrioid carcinoma: 0.6428; with a kappa value of 0.5372 for all cases combined. Interobserver agreement was in substantial rate for simple hyperplasia (SH) and well differentiated adenocarcinoma (WDA) but was in fair limit for complex hyperplasia (CH) and atypical hyperplasia (AH). Intraobserver agreement was almost perfect. The specimens were divided in two groups according to the computerized morphometric analysis: Endometrial Hyperplasia (EH) ( D Score ≥ 1 or VPS ≥ 55%) and Endometrial Intraepithelial Neoplasia (EIN) (D-Score < 1 or VPS < 55%). Morphometric findings were closely compatible with routine WHO classification made by one expert pathologist; however; diagnosis of (CH) and (AH) made by other pathologists were not concordant with morphometric data. Conclusion It may be necessary to make some revisions in WHO classification for endometrial hyperplasia and precancerous lesions.

Several studies have assumed that myoepithelial cells (MECs) loss may contribute to epithelial tumor induction and/or progression. We adopted an in vitro assay and a syngeneic mice breast cancer model with histological and molecular characteristics resembling human lesions to evaluate tumor suppression effects of MECs. Flow cytometric, cell viability, blood chemistry, transmission electron microscope, immunohistochemistry and qRT-PCR assays were performed at the end of the study. We demonstrated that MECs could significantly suppress the viability of cancer cells at different time points (P<0.05). At the end of the fourth and fifth weeks, treated mice had smaller tumor volume compared with control animals. Average tumor volume was significantly less in treated groups than control group at days 21 (0.38±0.19 vs. 1.99±0.13 cm3), 28 (0.57±0.3 vs. 2.5±0.37 cm3) and 35 (0.7±0.35 vs. 2.65±0.4 cm3) after tumor cell injection (P<0.05). No hematological, hepatocellular, and renal toxicities were seen in MECs treated groups. Ultrastructural features revealed severe relationship between adjacent tumoral cells and loose interconnections of neoplastic cells in treated group. Immunohistochemical examinations of breast tumors showed high p63 and low alpha-smooth muscle actin protein expression in treated mice compared to control (P<0.05). MRNA expressions of TNF-α, smooth muscle-myosin heavy chain, connexin 43, and maspin were significantly up-regulated in breast tumor tissues in treated group compared to control (P<0.05). VEGF and alpha-smooth muscle actin mRNA expression were reduced in treated animals (P<0.05). The present study highlighted the potential tumor suppression effects of MECs on breast cancer in a typical animal model., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Exercise training has an anti-tumor effect and can reduce tumor growth; however, the exact underlying mechanisms of its protective effects are still obscure. MicroRNA (miR)-21 is a predictor in cancer survival, and has a potential use as an indicator of therapeutic outcome in breast malignancies. Forty-eight female BALB/c mice were equally divided into six groups to investigate the effects of interval exercise training with tamoxifen on miR-21 expression and its possible assumed mechanisms in an estrogen receptor-positive breast cancer model. ELISA, immunohistochemistry, western blot, qRT-PCR assays were performed at the end of the study. Tumor size was significantly declined in exercise training and tamoxifen groups compared to tumor group (P<0.05). Expression of miR-21 was significantly down-regulated in trained and tamoxifen treated mice in comparison with tumor group (P<0.05). Exercise training was as effective as tamoxifen treatment in decreasing serum estradiol and ER-α expression (P<0.05). Exercise training and tamoxifen reduced tumor IL-6 levels, NF-kB and STAT3 expressions, and up-regulated TPM1 and PDCD4 expressions (P<0.05). Both exercise and tamoxifen had synergistic effects in reducing miR-21 and Bcl-2, and up-regulating PDCD4 expression. Results showed that interval exercise training may reduce mammary tumor burden in mice through possible underlying pathway of miR-21., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Curcumin has been shown to inhibit migration and invasion of cancer angiogenesis via interacting with key regulatory molecules like NF-κB. Rapidly metabolized and conjugated in the liver, curcumin has the limited systemic bioavailability. Previous results have shown a new light of potential biocompatibility, biodegradability, as well as anti-cancer effects of dendrosomal curcumin (DNC) in biological systems. The present study aims to deliberate the protective effects of DNC on metastatic breast tumor in vitro and in vivo. After the dosing procedure, twenty-seven female mice were divided into 40 and 80mg/kg groups of DNC, along with a control group to investigate the anti-metastatic effects of DNC on mammary tumor-bearing mice. In vitro results showed that the different concentrations of DNC reduced the migration and the adhesion of 4T1 cells after 24h (P<0.05). Under the dosing procedure, DNC was safe at 80mg/kg and lower doses. The treated DNC animals had a higher survival rate and lower metastatic signs (14%) compared to control (100%) (P<0.05). The metastatic tumors were more common in control mice than the treated groups in the lung, the liver and the sternum tissues. Animals treated with DNC had smaller tumor volume in comparison with control group (P<0.05). Final mean tumor volume reached to approximately 1.11, 0.31 and 0.27cm(3) in the control, and 40 and 80mg/kg DNC groups, respectively (P<0.05). Furthermore, suppression of NF-κB expression by DNC led to down-regulation of VEGF, COX-2, and MMP-9 expressions in the breast tumor, the lung, the brain, the spleen and the liver tissues (P<0.05). These outcomes indicate that dendrosomal curcumin has a chemoprotective effect on the breast cancer metastasis through suppression of NF-κB and its regulated gene products., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Application of nanoparticles has recently promising results for water insoluble agents like curcumin. In this study, we synthesized polymeric nanoparticle-curcumin (PNPC) and then showed its efficiency, drug loading, stability, and safety. Therapeutic effects of PNPC were also assessed on two cell lines and in an animal model of breast cancer. PNPC remarkably suppressed mammary and hepatocellular carcinoma cells proliferation (P < 0.05). Under the dosing procedure, PNPC was safe at 31.25 mg/kg and lower doses. Higher doses demonstrated minimal hepatocellular and renal toxicity in paraclinical and histopathological examinations. Tumor take rate in PNPC-treated group was 37.5% compared with 87.5% in control (P < 0.05). Average tumor size and weight were significantly lower in PNPC group than control (P < 0.05). PNPC increased proapoptotic Bax protein expression (P < 0.05). Antiapoptotic Bcl-2 protein expression, however, was lower in PNPC-treated animals than the control ones (P < 0.05). In addition, proliferative and angiogenic parameters were statistically decreased in PNPC-treated animals (P < 0.05). These results highlight the suppressing role for PNPC in in vitro and in vivo tumor growth models. Our findings provide credible evidence for superior biocompatibility of the polymeric nanocarrier in pharmacological arena together with an excellent tumor-suppressing response.

Subject: Survivin expression is correlated with tumor aggressiveness and severity in head and neck carcinoma. A polymorphism at position -31 (G/C) (rs 9904341) has been associated with cancer risk in several studies. We evaluated the correlation of this polymorphism with clinical manifestation of patients with tongue squamous cell carcinoma (SCC) in an Irananian population., Methods: Paraffin-embedded tissue sections from patients with tongue SCC (n=91) were evaluated for association between the survivin -31 (G/C) polymorphism and tumor staging, pathological grade, lymph node metastasis, tumor size, and recurrence of tumor., Results: There was a significant increase of presence of allele C in patients who were at stages III and IV compared to patients with lower stages [GC+CC vs. GG, p=0.025, odds ratio [OR] 2.76, 95% confidence interval [CI] [1.03-7.4]). In addition, presence of allele C was significantly decreased in patients with T1 tumor size compared to patients with larger tumor size (p=0.03, OR 0.6, 95% CI [0.2-2.03])., Conclusion: Presence of the C allele was significantly associated with tumor stage and size; therefore, survivin might be an important marker in the prognosis of tongue SCC that requires further investigation.

Curcumin is a potential natural anticancer drug with limited bioavailability due to the lack of solubility in aqueous solvents. The present study is designed to investigate the preventive effects of polymeric nanocarrier-curcumin (PNCC) on colon carcinogenesis in an azoxymethane-induced rat tumor. Forty rats were divided into control, curcumin- and PNCC-treated groups. Animals received azoxymethane (AOM) as a carcinogenic agent (15 mg/kg, s.c.) weekly for two consecutive weeks. They were given curcumin 0.2% and PNCC two weeks before till 14 weeks after the last injection of AOM. In the end, post euthanasia, the entire gastrointestinal tract was scrutinized for tumors, and the rest of the body for metastatic deposits. Tumor number, size and location were characterized. The histopathological and immunohistochemistry examinations were also performed on colon tissue. In vivo, curcumin nanoparticles inhibited colon cancer growth in animal model. The tumors incidence and number decreased by nanocurcumin comparison with control. Furthermore, the nuclear/cytoplasmic ratio, epithelial stratification, nuclear dispolarity, goblet depletion, structural abnormality, and the expression of Beta-catenin and Bcl-2 proteins were reduced in PNCC compared to others groups (P<0.05). In addition, Bax protein expression was significantly increased in PNCC in comparison with control and curcumin-treated groups (P<0.001). The present study demonstrated the potential anticancer effects of PNCC in a typical animal model. The results provide evidence that nanopolymeric curcumin exerts a significant chemopreventive effect on AOM-initiated colon cancer through cell proliferation inhibition and apoptosis induction. More investigations are needed to confirm its safety for human use., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objectives: Wound healing represents a dynamic physiological process influenced by many factors. The aim of the present study was to evaluate the effects of Teucrium polium honey on the wound healing and tensile strength in rat., Materials and Methods: Thirty-six Sprague-Dawley rats were randomly divided into four equal (n= 9) treatment and control groups. Two full-thickness wounds were made over the dorsal thoracic region according to the incision and excision models. Animals were treated with topical Teucrium polium honey twice a day post surgery until complete healing was achieved. Histopathology and tensiometry were then studied., Results: The wound healing process occurred faster in the incision model than excision ones (P< 0.05). Teucrium polium honey promoted wound contraction, closure time and tensile strength (P< 0.05). Histopathological study also showed relative epithelial proliferation, improved angiogenesis granulation, and fibrous connective tissue in Teucrium polium honey treated animals., Conclusion: The present study demonstrates that Teucrium polium honey can accelerate wound healing as well as tensile strength in rat skin wounds.

Unlabelled: Chondrosarcoma is one of the most difficult types of cancers to diagnose and treatment. Therefore, the development of a reliable animal model for chondrosarcoma would be a helpful tool to study of the tumor's growth and progression., Aim: We conducted this study to develop a chondrosarcoma on rat by graft of human chondrosarcoma tumor tissue., Methods: Fourteen male Sprague-Dawley rats equally divided in xenograft-implanted and control groups. On the lateral side of the right femur distal 1/3, 5 mm incision was done on the skin after animal anesthesia. Then, was drilled 3 mm on the bone and implanted the xenograft in the bone. Radiography was taken from the operated femur weekly until the fourth week and monthly for 3 months. Four animals of each group were sacrificed after 4 weeks of operation; femur was harvested for histopathological study., Results: Radiological images showed sclerotic area on the implanted bone after 4 weeks of operation. Sections from tumoral areas reveal cartilage forming hypercellular neoplastic tissue with lobular pattern of growth and foci of adjacent tissue invasion such as bone trabeculas and bone marrow., Conclusion: the present study showed that rat xenograft chondrosarcoma can develop by human chondrosarcoma fresh tissue fragments.

Background: Many studies have attempted to identify histologic features that help to distinguish atypical hyperplasia from hyperplasia without atypia and well-differentiated endometrioid carcinoma of the endometrium; however, few have evaluated the reproducibility of these diagnoses., Methods: Five pathologists independently reviewed 100 endometrial curettage specimens chosen to represent the spectrum of proliferative lesions of the endometrium. This included simple hyperplasia, complex hyperplasia, atypical hyperplasia, and well-differentiated endometrioid carcinoma. Slides were reviewed once for interobserver agreement among the five pathologists and twice for intraobserver agreement by one of them., Results: The results were assessed using the weighted kappa statistic. The mean intraobserver kappa value was 0.86. The mean interobserver kappa values by diagnostic category were as follows: simple hyperplasia without atypia: 0.74; complex hyperplasia without atypia: 0.33; atypical hyperplasia: 0.34, and well-differentiated endometrioid carcinoma: 0.64; with a kappa value of 0.53 for all cases combined., Conclusion: A major interobserver discrepancy exists in the diagnosis of complex and atypical hyperplasia which are the most similar mimics of endometrioid carcinoma.

Background: Management of endometrial precancerous lesions has been of much debate due to inconsistencies in their classification, natural history and histologic diagnosis. Endometrial hyperplasia constitutes a wide range of histomorphologic features associated with high intra and interobserver diagnostic variability.Although traditional microscopic diagnosis is by far the most applicable method and the gold standard for histomorphologic diagnosis, digitized image analysis has been used as a powerful adjunct to maximize the histologic data retrieval and to add some detailed objective criteria for correct diagnosis in difficult cases., Methods: A series of 100 endometrial curettage specimens with diagnosis of endometrial hyperplasia or well differentiated adenocarcinoma were blindly reviewed by 5 pathologists; their intra and interobserver reproducibility determined and further compared to the objective morphometric data i.e. D-score and volume percent of stroma (VPS)., Results: The results were assessed using the weighted kappa statistics. Mean intraobserver kappa value was 0.8690 (99.44% agreement). Mean interobserver kappa values by diagnostic category were: simple hyperplasia without atypia: 0.7441; complex hyperplasia without atypia: 0.3379; atypical hyperplasia: 0.3473, and well-differentiated endometrioid carcinoma: 0.6428; with a kappa value of 0.5372 for all cases combined.Interobserver agreement was in substantial rate for simple hyperplasia (SH) and well differentiated adenocarcinoma (WDA) but was in fair limit for complex hyperplasia (CH) and atypical hyperplasia (AH). Intraobserver agreement was almost perfect. The specimens were divided in two groups according to the computerized morphometric analysis: Endometrial Hyperplasia (EH) ( D Score > or = 1 or VPS > or = 55%) and Endometrial Intraepithelial Neoplasia (EIN) (D-Score < 1 or VPS < 55%). Morphometric findings were closely compatible with routine WHO classification made by one expert pathologist; however; diagnosis of (CH) and (AH) made by other pathologists were not concordant with morphometric data., Conclusion: It may be necessary to make some revisions in WHO classification for endometrial hyperplasia and precancerous lesions.