Search results for: mammary gland tumor

Authors: Navkiran Kaur, Apoorva Mathur, Abhishree Agarwal, Sakshi Gupta, Tuhin Rashmi

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Aim: Breast cancer is the most common cancer in women worldwide, and resistance to the current therapeutics, often concurrently, is an increasing clinical challenge. Glycosylation of proteins is one of the most important post-translational modifications. It is widely known that aberrant glycosylation has been implicated in many different diseases due to changes associated with biological function and protein folding. Alterations in cell surface glycosylation, can promote invasive behavior of tumor cells that ultimately lead to the progression of cancer. In breast cancer, there is an increasing evidence pertaining to the role of glycosylation in tumor formation and metastasis. In the present study, an attempt has been made to study the disease associated sialoglycoproteins in breast cancer by using bioinformatics tools. The sequence will be retrieved from UniProt database. A database in the form of a word document was made by a collection of FASTA sequences of breast cancer gene sequence. Glycosylation was studied using yinOyang tool on ExPASy and Differential genes expression and protein analysis was done in context of breast cancer metastasis. The number of residues predicted O-glc NAc threshold containing 50 aberrant glycosylation sites or more was detected and recorded for individual sequence. We found that the there is a significant change in the expression profiling of glycosylation patterns of various proteins associated with breast cancer. Differential aberrant glycosylated proteins in breast cancer cells with respect to non-neoplastic cells are an important factor for the overall progression and development of cancer.

Keywords: breast cancer, bioinformatics, cancer, metastasis, glycosylation

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Authors: Parveen Kundu, Nitika Chawla, Ruchi Agarwal, Swaran Kaur

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Background: Mature cystic teratoma is a benign, most common tumor of the ovary occurring mostly in young and middle-aged females. This study consists of 19 cases of mature cystic teratomas which were received in the Department Of Pathology over a period of two years. There were malignant transformations observed in three cases, which makes it very important for pathologists to thoroughly examine the entire specimen of mature cystic teratomas. Material and Methods: Nineteen reported cases of mature cystic teratomas were received in Deptt. Of Pathology, BPS GMC Khanpur Kalan, Sonepat, over a two-year period from November 2020 to October 2022 and reviewed retrospectively. Data regarding age, size, laterality, gross, morphological features, and surgery performed were retrieved from pathological archives. Results: In our study, the most common age of presentation was the 20-40 year age group. The most common presenting complaint was fullness in the abdomen or abdominal distension. Four out of 19 cases studied cases presented with bilateral ovarian cysts. Tumor size ranged from 6 to 20 cm in diameter. In seven cases, cysts were greater than or equal to 10 cm in diameter. Three cases showed malignant transformation. Conclusion: It is very important to thoroughly examine the contralateral ovary to rule out bilateral presentation. A furthermost thorough examination is advised in tumors of size >10 cm and in tumors with solid areas to rule out any malignant transformation.

Keywords: teratoma, ovary, malignant, transformation

Procedia PDF Downloads 67

Authors: S. Pradhan, D. Pradhan, G. Tripathy, T. Dasmohapatra

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Suppressors of cytokine signalling (SOCS3), a newly indentified anti-apoptotic molecule is a downstream effecter of the receptor tyrosine kinase-Ras signalling pathway. Current study has uncovered that SOCS3 may have wide and imperative capacities, particularly because of its close correlation with malignant tumors. To investigate the impact of SOCS3 on MDR, we analyzed the expression of P-gp and SOCS3 by immune-histochemistry and found there was positive correlation between them. At that point we effectively interfered with RNA translation by the contamination of siRNA of SOCS3 into MCF7/ADM breast cancer cell lines through a lentivirus, and the expression of the target gene was significantly inhibited. After RNAi the drug resistance was reduced altogether and the expression of MDR1 mRNA and P-gp in MCF7/ADM cell lines demonstrated a significant decrease. Likewise the expression of P53 protein increased in a statistically significant manner (p ≤ 0.01) after RNAi exposure. Moreover, flowcytometry analysis uncovers that cell cycle and anti-apoptotic enhancing capacity of cells changed after RNAi treatment. These outcomes proposed SOCS3 may take part in breast cancer MDR by managing MDR1 and P53 expression, changing cell cycle and enhancing the anti-apoptotic ability.

Keywords: SOCS3gene, breast cancer, multidrug resistance, MDR1 gene, RNA interference

Procedia PDF Downloads 317

Authors: Emma J. Dale, Christina D. Buesching, Kevin R. Theis, David W. Macdonald

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This study investigates the oral and intestinal microbiomes of wild-living European badgers (Meles meles) and will relate inter-individual differences to social contact networks, somatic and reproductive fitness, varying susceptibility to bovine tuberculous (bTB) and to the olfactory advertisement. Badgers are an interesting model for this research, as they have great variation in body condition, despite living in complex social networks and having access to the same resources. This variation in somatic fitness, in turn, affects breeding success, particularly in females. We postulate that microbiota have a central role to play in determining the successfulness of an individual. Our preliminary results, characterising the microbiota of individual badgers, indicate unique compositions of microbiota communities within social groups of badgers. This basal information will inform further questions related to the extent microbiota influence fitness. Hitherto, the potential role of microbiota has not been considered in determining host condition, but also other key fitness variables, namely; communication and resistance to disease. Badgers deposit their faeces in communal latrines, which play an important role in olfactory communication. Odour profiles of anal and subcaudal gland secretions are highly individual-specific and encode information about group-membership and fitness-relevant parameters, and their chemical composition is strongly dependent on symbiotic microbiota. As badgers sniff/ lick (using their Vomeronasal organ) and over-mark faecal deposits of conspecifics, these microbial communities can be expected to vary with social contact networks. However, this is particularly important in the context of bTB, where badgers are assumed to transmit bTB to cattle as well as conspecifics. Interestingly, we have found that some individuals are more susceptible to bTB than are others. As acquired immunity and thus potential susceptibility to infectious diseases are known to depend also on symbiotic microbiota in other members of the mustelids, a role of particularly oral microbiota can currently not be ruled out as a potential explanation for inter-individual differences in infection susceptibility of bTB in badgers. Tri annually badgers are caught in the context of a long-term population study that began in 1987. As all badgers receive an individual tattoo upon first capture, age, natal as well as previous and current social group-membership and other life history parameters are known for all animals. Swabs (subcaudal ‘scent gland’, anal, genital, nose, mouth and ear) and fecal samples will be taken from all individuals, stored at -80oC until processing. Microbial samples will be processed and identified at Wayne State University’s Theis (Host-Microbe Interactions) Lab, using High Throughput Sequencing (16S rRNA-encoding gene amplification and sequencing). Acknowledgments: Gas-Chromatography/ Mass-spectrometry (in the context of olfactory communication) analyses will be performed through an established collaboration with Dr. Veronica Tinnesand at Telemark University, Norway.

Keywords: communication, energetics, fitness, free-ranging animals, immunology

Procedia PDF Downloads 164

Authors: Amjad Al Shammari, Ashraf Ibrahim, Laila Seada

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Background and Objectives: Incidence of thyroid carcinoma has been increasing world-wide. In the present study, we evaluated diagnostic accuracy of Fine needle aspiration (FNA) and its efficiency in early detecting neoplastic lesions of thyroid gland over a 3-year period. Methods: Data have been retrieved from pathology files in King Khalid Hospital. For each patient, age, gender, FNA, site & size of nodule and final histopathologic diagnosis were recorded. Results: Study included 490 cases where 419 of them were female and 71 male. Male to female ratio was 1:6. Mean age was 43 years for males and 38 for females. Cases with confirmed histopathology were 131. In 101/131 (77.1%), concordance was found between FNA and histology. In 30/131 (22.9%), there was discrepancy in diagnosis. Total malignant cases were 43, out of which 14 (32.5%) were true positive and 29 (67.44%) were false negative. No false positive cases could be found in our series. Conclusion: FNA could diagnose benign nodules in all cases, however, in malignant cases, ultrasound findings have to be taken into consideration to avoid missing of a microcarcinoma in the contralateral lobe.

Keywords: FNA, hail, histopathology, thyroid

Procedia PDF Downloads 315

Authors: Ugo Rovigatti

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Neuroblastoma (NBL) has epitomized for at least 40 years our understanding of cancer cellular and molecular biology and its potential applications to novel therapeutic strategies. This includes the discovery of the very first oncogene aberrations and tumorigenesis suppression by differentiation in the 80s; the potential role of suppressor genes in the 90s; the relevance of immunotherapy in the millennium first, and the discovery of additional mutations by NGS technology in the millennium second decade. Similar discoveries were achieved in the majority of human cancers, and similar therapeutic interventions were obtained subsequently to NBL discoveries. Unfortunately, targeted therapies suggested by specific mutations (such as MYCN amplification –MNA- present in ¼ or 1/5 of cases) have not elicited therapeutic successes in aggressive NBL, where the prognosis is still dismal. The reasons appear to be linked to Tumor Heterogeneity, which is particularly evident in NBL but also a clear hallmark of aggressive human cancers generally. The new avenue of cancer immunotherapy (CIT) provided new hopes for cancer patients, but we still ignore the cellular or molecular targets. CIT is emblematic of high-risk disease (HR-NBL) since the mentioned GD2 passive immunotherapy is still providing better survival. We recently critically reviewed and evaluated the literature depicting the genomic landscapes of HR-NBL, coming to the qualified conclusion that among hundreds of affected genes, potential targets, or chromosomal sites, none correlated with anti-GD2 sensitivity. A better explanation is provided by the Micro-Foci inducing Virus (MFV) model, which predicts that neuroblasts infection with the MFV, an RNA virus isolated from a cancer-cluster (space-time association) of HR-NBL cases, elicits the appearance of MNA and additional genomic aberrations with mechanisms resembling chromothripsis. Neuroblasts infected with low titers of MFV amplified MYCN up to 100 folds and became highly transformed and malignant, thus causing neuroblastoma in young rat pups of strains SD and Fisher-344 and larger tumor masses in nu/nu mice. An association was discovered with GD2 since this glycosphingolipid is also the receptor for the family of MFV virus (dsRNA viruses). It is concluded that a dsRNA virus, MFV, appears to provide better explicatory mechanisms for the genesis of i) specific genomic aberrations such as MNA; ii) extensive tumor heterogeneity and chromothripsis; iii) the effects of passive immunotherapy with anti-GD2 monoclonals and that this and similar models should be further investigated in both pediatric and adult cancers.

Keywords: neuroblastoma, MYCN, amplification, viruses, GD2

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Authors: Brajesh Tiwari, Yuvraj Dangi, Abhishek Jain, Ashok Jain

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The purpose of the investigation was to evaluate the potential of sphingosomes as nanoscale drug delivery units for site-specific delivery of anti-cancer agents. Doxorubicin Hydrochloride (DOX) was selected as a model anti-cancer agent. Sphingosomes were prepared and loaded with DOX and optimized for size and drug loading. The formulations were characterized by Malvern zeta-seizer and Transmission Electron Microscopy (TEM) studies. Sphingosomal formulations were further evaluated for in-vitro drug release study under various pH profiles. The in-vitro drug release study showed an initial rapid release of the drug followed by a slow controlled release. In vivo studies of optimized formulations and free drug were performed on albino rats for comparison of drug plasma concentration. The in- vivo study revealed that the prepared system enabled DOX to have had enhanced circulation time, longer half-life and lower elimination rate kinetics as compared to free drug. Further, it can be interpreted that the formulation would selectively enter highly porous mass of tumor cells and at the same time spare normal tissues. To summarize, the use of sphingosomes as carriers of anti-cancer drugs may prove to be a fascinating approach that would selectively localize in the tumor mass, increasing the therapeutic margin of safety while reducing the side effects associated with anti-cancer agents.

Keywords: sphingosomes, anti-cancer, doxorubicin, formulation

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Authors: Karen Boaz, C. R. Charan

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Background: The infiltration of tumour stroma by eosinophils, Tumor-Associated Tissue Eosinophilia (TATE), is known to modulate the progression of Oral Squamous Cell Carcinoma (OSCC). Eosinophils have direct tumoricidal activity by release of cytotoxic proteins and indirectly they enhance permeability into tumor cells enabling penetration of tumoricidal cytokines. Also, eosinophils may promote tumor angiogenesis by production of several angiogenic factors. Identification of eosinophils in the inflammatory stroma has been proven to be an important prognosticator in cancers of mouth, oesophagus, larynx, pharynx, breast, lung, and intestine. Therefore, the study aimed to correlate TATE with clinical and histopathological variables, and blood eosinophil count to assess the role of TATE as a prognosticator in Oral Squamous Cell Carcinoma (OSCC). Methods: Seventy two biopsy-proven cases of OSCC formed the study cohort. Blood eosinophil counts and TNM stage were obtained from the medical records. Tissue sections (5µm thick) were stained with Haematoxylin and Eosin. The eosinophils were quantified at invasive tumour front (ITF) in 10HPF (40x magnification) with an ocular grid. Bryne’s grading of ITF was also performed. A subset of thirty cases was also assessed for association of TATE with recurrence, involvement of lymph nodes and surgical margins. Results: 1) No statistically significant correlation was found between TATE and TNM stage, blood eosinophil counts and most parameters of Bryne’s grading system. 2) Statistically significant relation of intense degree of TATE was associated with the absence of distant metastasis, increased lympho-plasmacytic response and increased survival (diseasefree and overall) of OSCC patients. 3) In the subset of 30 cases, tissue eosinophil counts were higher in cases with lymph node involvement, decreased survival, without margin involvement and in cases that did not recur. Conclusion: While the role of eosinophils in mediating immune responses seems ambiguous as eosinophils support cell-mediated tumour immunity in early stages while inhibiting the same in advanced stages, TATE may be used as a surrogate marker for determination of prognosis in oral squamous cell carcinoma.

Keywords: tumour-associated tissue eosinophilia, oral squamous cell carcinoma, prognosticator, tumoral immunity

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Authors: Aleksandra Chałupnik, Zuzanna Chilimoniuk, Joanna Borowik, Aleksandra Borkowska, Anna Torres

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Background: Precocious puberty is the occurrence of secondary sexual characteristics in girls before the age of 8. The diverse etiology of premature puberty is crucial to determine whether it is true precocious puberty, depending on the activation of the hypothalamic-pituitary-gonadal axis, or pseudo-precocious, which is independent of the activation of this axis. Whatever the cause, premature action of the sex hormones leads to the common symptoms of various forms of puberty. These include the development of sexual characteristics, acne, acceleration of growth rate and acceleration of skeletal maturation. Due to the possible genetic basis of the disorders, an interdisciplinary search for the cause is needed. Case report: The case report concerns a patient of a pediatric gynecology clinic who, at the age of two years, developed advanced thelarhe (M3) and started recurrent vaginal bleeding. In August 2019, gonadotropin suppression initially and after LHRH stimulation and high estradiol levels were reported at the Endocrinology Department. Imaging examinations showed a cyst in the right ovary projection. The bone age was six years. The entire clinical picture indicated pseudo- (peripheral) precocious in the course of ovarian autonomic cyst. In the follow-up ultrasound performed in September, the image of the cyst was stationary and normalization of estradiol levels and clinical symptoms was noted. In December 2019, cyst regression and normal gonadotropin and estradiol concentrations were found. In June 2020, white mucus tinged with blood on the underwear, without any other disturbing symptoms, was observed for several days. Two consecutive USG examinations carried out in the same month confirmed the change in the right ovary, the diameter of which was 25 mm with a very high level of estradiol. Germinal tumor markers were normal. On the Tanner scale, the patient scored M2P1. The labia and hymen had puberty features. The correct vaginal entrance was visible. Another active vaginal bleeding occurred in the first week of July 2020. The considered laparoscopic treatment was abandoned due to the lack of oncological indications. Treatment with Tamoxifen was recommended in July 2020. In the initiating period of treatment, no maturation progression, and even reduction of symptoms, no acceleration of growth and a marked reduction in the size of the cysts were noted. There was no bleeding. After the size of the cyst and hormonal activity increased again, the treatment was changed to Anastrozole, the effect of which led to a reduction in the size of the cyst. Conclusions: The entire clinical picture indicates alleged (peripheral) puberty. Premature puberty in girls, which is manifested as enlarged mammary glands with high levels of estrogens secreted by autonomic ovarian cysts and prepubertal levels of gonadotropins, may indicate McCune-Albright syndrome. Vaginal bleeding may also occur in this syndrome. Cancellation of surgical treatment of the cyst made it impossible to perform a molecular test that would allow to confirm the diagnosis. Taking into account the fact that cysts are often one of the first symptoms of McCune-Albrigt syndrome, it is important to remember about multidisciplinary care for the patient and careful search for skin and bone changes or other hormonal disorders.

Keywords: McCune Albrigth's syndrome, ovarian cyst, pediatric gynaecology, precocious puberty

Procedia PDF Downloads 168

Authors: Debasish Pradhan, Shaktiprasad Pradhan, Rakesh Kumar Pradhan, Gitanjali Tripathy

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Suppressors of cytokine signalling (SOCS1), a newly indentified antiapoptotic molecule is a downstream effector of the receptor tyrosine kinase-Ras signalling pathway. The current study has uncovered that SOCS1 may have wide and imperative capacities, particularly because of its close correlation with malignant tumors. To investigate the impact of SOCS1 on MDR, we analyzed the expression of P-gp and SOCS1 by immunohistochemistry and found there was a positive correlation between them. At that point, we effectively interfered with RNA translation by the contamination of siRNA of SOCS1 into MCF7/ADM breast cancer cell lines through a lentivirus, and the expression of the target gene was significantly inhibited. After RNAi, the drug resistance was reduced altogether and the expression of MDR1 mRNA and P-gp in MCF7/ADM cell lines demonstrated a significant decrease. Likewise, the expression of P53 protein increased in a statistically significant manner (p ≤ 0.01) after RNAi exposure. Moreover, flow cytometry analysis uncovers that cell cycle and anti-apoptotic enhancing capacity of cells changed after RNAi treatment. These outcomes proposed SOCS1 may take part in breast cancer MDR by managing MDR1 and P53 expression, changing cell cycle and enhancing the anti-apoptotic ability.

Keywords: breast cancer, multidrug resistance, SOCS1 gene, MDR1 gene, RNA interference

Procedia PDF Downloads 340

Authors: Tefera Worku Mekonnen, Hiseh Chih Tsai

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Enhancement of drug efficacy is essential in cancer treatment. The immune stimulator ovalbumin (Ova)-coated citric acid (AC-)-stabilized iron oxide nanoparticles (AC-IO-Ova NPs) and enhanced permeability and retention (EPR) based tumor targeted 4.5 (4.5G) poly(amidoamine) dendrimer-cisplatin nanocomplex (4.5GDP-Cis-pt NC) were used for enhanced anticancer efficiency. The formations of 4.5GDP-Cis-pt NC, AC-IO, and AC-IO-Ova NPs have been examined by FTIR, X-ray diffraction, Raman, and X-ray photoelectron spectroscopy. The conjugation of cisplatin (Cis-pt) with 4.5GDP was confirmed using carbon NMR. The tumor-specific 4.5GDP-Cis-pt NC provided ~45% and 28% cumulative cisplatin release in 72 h at pH 6.5 and 7.4, respectively. A significant immune response with high TNF-α and IL-6 cytokine secretion was confirmed when the co-incubation of AC-IO-Ova with RAW 264.7 or HaCaT cells. AC-IO-Ova NP was biocompatible in different cell lines, even at a high concentration (200 µg mL−1). In contrast, AC-IO-Ova NPs mixed with 4.5GDP-Cis-pt NC (Cis-pt at 15 µg mL−1) significantly increased the cytotoxicity against the cancer cells, which is dose-dependent on the concentration of AC-IO-Ova NPs. The increased anticancer effects may be attributed to the generation of reactive oxygen species (ROS). Moreover, the efficiency of anticancer cells may be further assisted by induction of an innate immune response via M1 macrophage polarization due to the presence of AC-IO-Ova NPs. We provide a better synergestic chemoimmunotherapeutic strategy to enhance the efficiency of anticancer of cisplatin via chemotherapeutic agent 4.5GDP-Cis-pt NC and induction of proinflammatory cytokines to stimulate innate immunity through AC-IO-Ova NPs against tumors.

Keywords: cisplatin-release, iron oxide, ovalbumin, poly(amidoamine) dendrimer

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Authors: Ratchaneewan Salao, Steven W. Edwards, Kiatichai Faksri, Kanin Salao

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Background: A two-dose regimen of COVID-19 vaccination (inactivated whole virion SARS-CoV-2 and adenoviral vector) has been widely used. Side effects are very low, but several adverse effects have been reported. Methods: A 40-year-old female patient, with a previous history of thyroid goitre, developed severe neck pain, headache, nausea and fatigue 7-days after receiving second vaccination with Vaxzevria® (Oxford-AstraZeneca). Clinical and laboratory findings, including thyroid function tests and ultrasound of thyroid glands, were performed. Results: Her left thyroid gland was multinodular enlarged, and severely tender on palpation. She had difficulty in swallowing and had tachycardia but no signs of hyperthyroidism. Laboratory results supported a diagnosis of subacute thyroiditis. She was prescribed NSAID (Ibuprofen 400 mg) and dexamethasone for 3-days and her symptoms resolved. Conclusions: Although this is an extremely rare event, physicians may encounter more cases of this condition due to the extensive vaccination program using this combination of vaccines.

Keywords: SARS-CoV-2, adenoviral vector vaccines, vaccination, subacute thyroiditis

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Authors: Sanjukta Badhai, Durga Barik, Bairagi C. Mallick

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In the present study, Beta-Sitosterol in Lawsonia methanolic leaf extract embedded in controlled release nanocomposite was prepared and evaluated for in vivo anticancer efficacy in dimethyl hydrazine (DMH) induced colon cancer. In the present study, colon cancer was induced by s.c injection of DMH (20 mg/kg b.wt) for 15 weeks. The animals were divided into five groups as follows control, DMH alone, DMH and Beta Sitosterol nanocomposite (50mg/kg), DMH and Beta Sitosterol nanocomposite (100 mg/kg) and DMH and Standard Silymarin (100mg/kg) and the treatment was carried out for 15 weeks. At the end of the study period, the blood was withdrawn, and serum was separated for haematological, biochemical analysis and tumor markers. Further, the colonic tissue was removed for the estimation of antioxidants and histopathological analysis. The results of the study displays that DMH intoxication elicits altered haematological parameters (RBC,WBC, and Hb), elevated lipid peroxidation and decreased antioxidants level (SOD, CAT, GPX, GST and GSH), elevated lipid profiles (cholesterol and triglycerides), tumor markers (CEA and AFP) and altered colonic tissue histology. Meanwhile, treatment with Beta Sitosterol nanocomposites significantly restored the altered biochemicals parameters in DMH induced colon cancer mediated by its anticancer efficacy. Further, Beta Sitosterol nanocomposite (100 mg/kg) showed marked efficacy.

Keywords: nanocomposites, herbal formulation, henna, beta sitosterol, colon cancer, dimethyl hydrazine, antioxidant, lipid peroxidation

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Authors: Nasrin Hosseinzad, Ramin Ghasemi Shayan

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Chemotherapy is the most common procedure in the treatment of advanced cancers but is justsoberlyoperativeand toxic. Nevertheless, the efficiency of chemotherapy is restrictedowing to multiple drug resistance(MDR). Lately, plentiful preclinical experiments have revealedthatPaclitaxel-Curcumin could be an ultimateapproach to converse MDR and synergistically increase their efficiency. The connotationsamongst B-cell-lymphoma2(BCL-2) and multi-drug-resistance-associated-P-glycoprotein(MDR1) consequence of patients forecast the efficiency of paclitaxel-built chemoradiotherapy. There are evidences of the efficacy of paclitaxel in the treatment of surface-transmission of bladder-cell-carcinoma by manipulating bio-adhesive microspheres accomplishedthroughout measured release of drug at urine epithelium. In Genetically-Modified method, muco-adhesive oily constructionoftricaprylin, Tween 80, and paclitaxel group showed slighter toxicity than control in therapeutic dose. Postoperative chemotherapy-Paclitaxel might be more advantageous for survival than adjuvant chemo-radio-therapy, and coulddiminish postoperative complications in cervical cancer patients underwent a radical hysterectomy.HA-Se-PTX(Hyaluronic acid, Selenium, Paclitaxel) nanoparticles could observablyconstrain the proliferation, transmission, and invasion of metastatic cells and apoptosis. Furthermore, they exhibitedvast in vivo anti-tumor effect. Additionally, HA-Se-PTX displayedminor toxicity on mice-chef-organs. Briefly, HA-Se-PTX mightprogress into a respectednano-scale agentinrespiratory cancers. To sum up, Paclitaxel is considered a profitable anti-cancer drug in the treatment and anti-progress symptoms in malignant cancers.

Keywords: cancer, paclitaxel, chemotherapy, tumor

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Authors: B. Petrović, M. Petrović, L. Rutonjski, I. Djan, V. Ivanović

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Objective: Cardiac pacemakers are very sensitive to radiotherapy treatment from two sources: electromagnetic influence from the medical linear accelerator producing ionizing radiation- influencing electronics within the pacemaker, and the absorption of dose to the device. On the other hand, patients with cardiac pacemakers at the place of a tumor are rather rare, and single clinic hardly has experience with the management of such patients. The widely accepted international guidelines for management of radiation oncology patients recommend that these patients should be closely monitored and examined before, during and after radiotherapy treatment by cardiologist, and their device and condition followed up. The number of patients having both cancer and pacemaker, is growing every year, as both cancer incidence, as well as cardiac diseases incidence, are inevitably growing figures. Materials and methods: Female patient, age 69, was diagnozed with valvular cardiomyopathy and got implanted a pacemaker in 2005 and prosthetic mitral valve in 1993 (cancer was diagnosed in 2012). She was stable cardiologically and came to radiation therapy department with the diagnosis of right breast cancer, with the tumor in upper lateral quadrant of the right breast. Since she had all lymph nodes positive (28 in total), she had to have irradiated the supraclavicular region, as well as the breast with the tumor bed. She previously received chemotherapy, approved by the cardiologist. The patient was estimated to be with the high risk as device was within the field of irradiation, and the patient had high dependence on her pacemaker. The radiation therapy plan was conducted as 3D conformal therapy. The delineated target was breast with supraclavicular region, where the pacemaker was actually placed, with the addition of a pacemaker as organ at risk, to estimate the dose to the device and its components as recommended, and the breast. The targets received both 50 Gy in 25 fractions (where 20% of a pacemaker received 50 Gy, and 60% of a device received 40 Gy). The electrode to the heart received between 1 Gy and 50 Gy. Verification of dose planned and delivered was performed. Results: Evaluation of the patient status according to the guidelines and especially evaluation of all associated risks to the patient during treatment was done. Patient was irradiated by prescribed dose and followed up for the whole year, with no symptoms of failure of the pacemaker device during, or after treatment in follow up period. The functionality of a device was estimated to be unchanged, according to the parameters (electrode impedance and battery energy). Conclusion: Patient was closely monitored according to published guidelines during irradiation and afterwards. Pacemaker irradiated with the full dose did not show any signs of failure despite recommendations data, but in correlation with other published data.

Keywords: cardiac pacemaker, breast cancer, radiotherapy treatment planning, complications of treatment

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Authors: Ahlem Bahi, Youcef Necib, Sakina Zerizer, Cherif Abdennour, Mohamed Salah Boulakoud

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Mercury (II) is a highly toxic metal which induces oxidative stress in the body. In this study, we aimed to investigate the possible protective effect of olive oil, an antioxidant agent, against experimental mercury toxicity in rat model. Administration of mercuric chloride induced significant increase in serum: ALT, AST, and LPA activities; interleukine1, interleukine6, tumor necrosis factor α (TNFα), creatinine, urea, and uric acid levels. Mercuric chloride also induced oxidative stress, as indicate by decreased tissue of GSH level, GSH-Px, and GST activities along with increase the level of lipid peroxidation. Furthermore, treatment with mercuric chloride caused a marked elevation of kidney and liver weight and decreased body weight. Virgin olive oil treatment markedly reduced elevated serum: AST, ALT, and LPA activities; interleukine1, interleukine6, tumor necrosis factor α (TNFα), creatinine, urea, and uric acid levels and contracted the deterious effects of mercuric chloride on oxidative stress markers changes caused by HgCl2 in tissue as compared to control group. Our results implicate that mercury induced oxidative damage in liver and kidney tissue protected by virgin olive oil, with its antioxidant effects.

Keywords: mercury, antioxidant enzymes, pro-inflammatory cytokine, virgin olive oil, lipid peroxidation

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Authors: Reham H. Soliman, Noha Noufal, Howayda AbdelAal

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Calcium/calmodulin-dependent serine protein kinase (CASK) belongs to the membrane-associated guanylate kinase (MAGUK) family and has been proposed as a mediator of cell-cell adhesion and proliferation, which can contribute to tumorogenesis. CASK has been linked as a good prognostic factor with some tumor subtypes, while considered as a poor prognostic marker in others. To our knowledge, no sufficient evidence of CASK role in colorectal cancer is available. The aim of this study is to evaluate the expression of Calcium/calmodulin-dependent serine protein kinase (CASK) in non-mucinous colorectal adenocarcinoma and adenomatous polyps as precursor lesions and assess its prognostic significance. The study included 42 cases of conventional colorectal adenocarcinoma and 15 biopsies of adenomatous polyps with variable degrees of dysplasia. They were reviewed for clinicopathological prognostic factors and stained by CASK; mouse, monoclonal antibody using heat-induced antigen retrieval immunohistochemical techniques. The results showed that CASK protein was significantly overexpressed (p <0.05) in CRC compared with adenoma samples. The CASK protein was overexpressed in the majority of CRC samples with 85.7% of cases showing moderate to strong expression, while 46.7% of adenomas were positive. CASK overexpression was significantly correlated with both TNM stage and grade of differentiation (p <0.05). There was a significantly higher expression in tumor samples with early stages (I/II) rather than advanced stage (III/IV) and with low grade (59.5%) rather than high grade (40.5%). Another interesting finding was found among the adenomas group, where the stronger intensity of staining was observed in samples with high grade dysplasia (33.3%) than those of lower grades (13.3%). In conclusion, this study shows that there is significant overexpression of CASK protein in CRC as well as in adenomas with high grade dysplasia. This indicates that CASK is involved in the process of carcinogenesis and functions as a potential trigger of the adenoma-carcinoma cascade. CASK was significantly overexpressed in early stage and low-grade tumors rather than tumors with advanced stage and higher histological grades. This suggests that CASK protein is a good prognostic factor. We suggest that CASK affects CRC in two different ways derived from its physiology. CASK as part of MAGUK family can stimulate proliferation and through its cell membrane localization and as a mediator of cell-cell adhesion might contribute in tumor confinement and localization.

Keywords: CASK, colorectal cancer, overexpression, prognosis

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Authors: Bahadir Batar, Elif Serdal, Berna Erdal, Hasan Ogul

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Micro-ribonucleic acids (miRNAs) are small short non-coding ribonucleic acid molecules about 22 nucleotides long. miRNAs play a key role in response to chemotherapeutic agents. WW domain-containing oxidoreductase (WWOX) gene encodes a tumor suppressor protein. Loss or reduction of Wwox protein is observed in many breast cancer cases. WWOX protein deficiency is increased in triple-negative breast cancer (TNBC). TNBC is a heterogeneous, highly aggressive, and difficult to treat tumor type. WWOX loss contributes to resistance to cisplatin therapy in patients with TNBC. Here, the aim of the study was to investigate the potential role of miRNAs in cisplatin therapy resistance of WWOX-deficient TNBC cells. This was a cell culture study. miRNA expression profiling was analyzed by LightCycler 480 system. miRNA Set Enrichment Analysis tool was used to integrate experimental data with literature-based biological knowledge to infer a new hypothesis. Increased miR-182 and decreased miR-214 were significantly correlated with cisplatin resistance in WWOX-deficient TNBC cells. miR-182 and miR-214 may involve in cisplatin resistance of WWOX-deficient TNBC cells by deregulating the DNA repair, apoptosis, or protein kinase B signaling pathways. These data highlight the mechanism by which WWOX regulates cisplatin resistance of TNBC and the potential use of WWOX as a predictor biomarker for cisplatin resistance.

Keywords: cisplatin, microRNA, triple-negative breast cancer, WWOX

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Authors: Rajish Shil, Mohammad Ali Houri, Mohammad Milad Ismail, Fatimah Al Kaabi

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The clinical presentation of Primary hyperparathyroidism can vary from simple asymptomatic hypercalcemia to severe life-threatening hypercalcemic crisis with multi-organ dysfunction, which can be due to parathyroid adenoma or sometimes with malignant cancer. This cascade of clinical presentation can lead to a diagnostic and therapeutic challenge for treating the disease. We are presenting a case of severe hypercalcemic crisis due to parathyroid adenoma with an emphasis on early management, diagnosis, and interventions to prevent any lifelong complications and any permanent organ dysfunction. A 30 years old female with a history of primary Infertility, admitted to Al Ain Hospital critical care unit with Acute Severe Necrotizing Pancreatitis. She initially had a 1-month history of abdominal pain on and off, for which she was treated conservatively with no much improvement, and later on, she developed life-threatening severe pancreatitis, which required her to be admitted to the critical care unit. She was transferred from a private healthcare facility, where she was found to have a very high level of calcium up to 15mmol/L. She received systemic Zoledronic Acid, which lowered her calcium level transiently and later was increased again. She went on to develop multiple end-organ damages along with multiple electrolytes disturbances. She was found to have high levels of Parathyroid hormone, which was correlated with a parathyroid mass on the neck via radiological imaging. After a long course of medical treatment to lower the calcium to a near-normal level, parathyroidectomy was done, which showed parathyroid adenoma on histology. She developed hungry bone syndrome after the surgery and pancreatic pseudocyst after resolving of pancreatitis. She required aggressive treatment with Intravenous calcium for her hypocalcemia as she received zoledronic acid at the beginning of the disease. Later on, she was discharged on long term calcium and other electrolytes supplements. In patients presenting with hypercalcemia, it is prudent to investigate and start treatment early to prevent complications and end-organ damage from hypercalcemia and also to treat the primary cause of the hypercalcemia, with conscious follow up to prevent hypocalcemic complications after treatment. It is important to follow up patients with parathyroid adenomas for a long period in order to detect any recurrence of the tumor or to make sure if the primary tumor is either benign or malignant.

Keywords: hypercalcemia, pancreatitis, hypocalcemia, hyperparathyroidism

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Authors: Robin L. Rohrer

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Introduction: Pre-natal or early childhood exposure to the medical radiation used in diagnosis or treatment is an identified risk for childhood cancers but can be difficult to document. The author developed a family questionnaire/interview form to identify possible exposures. Aims: This retrospective study examines pre-natal and early childhood medical radiation exposure in a cohort of children diagnosed with a solid tumor including brain tumors from 1985-2015 at the Children’s Hospital of Pittsburgh (CHP). The hospital is a tri-state regional referral center which treats about 150-180 new cases of cancer in children per year. About 70% are diagnosed with a solid tumor. Methods: Each consented family so far (approximately 50% of the cohort) has been interviewed in person or by the phone call. Medical staff and psycho- social staff referred patient families for the interview with the author. Results: Among the families interviewed to date at least one medical radiation exposure has been identified (pre-conception, pre-natal or early childhood) in over 70% of diagnosed children. These exposures have included pre-conception sinus or chest CT or X-ray in either parent, sinus CT or X-ray in the mother or diagnostic radiation of chest or abdomen in children. Conclusions: Exposures to medical radiation for a child later diagnosed with cancer may occur at several critical junctures. These exposures may well contribute to a ‘perfect storm’ in the still elusive causes of childhood cancer. The author plans to expand the study from 1975 to present to hopefully further document these junctures.

Keywords: pediatric, solid tumors, medical radiation, cancer

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Authors: Savita Dixit

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Rutin is the bioactive flavonoid isolated from the straw part of Triticum aestivum and possess various pharmacological applications. The aim of this study is to evaluate the chemopreventive potential of rutin in an experimental skin carcinogenesis mice model system. Skin tumor was induced by topical application of 7, 12-dimethyl benz(a) anthracene (DMBA) and promoted by croton oil in Swiss albino mice. To assess the chemopreventive potential of rutin, it was orally administered at a concentration of (200 mg/kg and 400 mg/kg body weight) continued three times weekly for 16th weeks. The development of skin carcinogenesis was assessed by histopathological analysis. Reductions in tumor size and cumulative number of papillomas were seen due to rutin treatment. Average latent period was significantly increased as compared to carcinogen-treated control. Rutin produced a significant decrease in the activity of serum enzyme serum glutamate oxalate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), alkaline phosphatase (ALP) and bilirubin when compared with the control. They significantly increased the levels of enzyme involved in oxidative stress glutathione (GSH), superoxide dismutase (SOD) and catalase. The elevated level of lipid peroxidase in the control group was significantly inhibited by rutin administration. The results of the present study suggest the chemopreventive effect of rutin in DMBA and croton oil-induced skin carcinogenesis in swiss albino mice and one of the probable reasons would be its antioxidant potential.

Keywords: chemoprevention, papilloma, rutin, skin carcinogenesis

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Authors: Abdullah Saeidi, Aydin Gülses, Christan Flörke

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Skin cancer of the face region is the most common type of malignancy and surgical excision is the preferred approach. However, the clinical long term results reported in the literature are still controversial. Objectives: To describe; 1. Demographical characteristics 2. Affected site, distribution and TNM classification regarding tumor type 3. Surgical aspects • Surgical removal: excision principles, safety margins, the need for secondary resection, primary reconstruction/ defect closure, anesthesia protocol, duration of hospital stay (if any) • Secondary intervention for defect closure/reconstruction: Flap technique, anesthesia protocol, duration of hospital stay (if any), postoperative wound management etc. 4. Tumor recurrences 5. Clinical outcomes 6. Studying the possible therapy approach throw Biostatistical relation and correlation between multiple Histological, diagnostics and clinical Faktors. following surgical ablation of the skin cancer of the head and neck region. Methods: Selection and statistical analysis of medical records of patients who had admitted to the Department of Oral and Maxillofacial Surgery, Universitätsklinikum Schleswig Holstein, Campus Kiel during the period of 2015-2019 will be retrospectively evaluated. Data will be collected via ORBIS Information-Management-System (ORBIS AG, Saarbrücken, Germany).

Keywords: non melanoma skin cancer, face skin cancer, skin reconstruction, non melanoma skin cancer recurrence, non melanoma skin cancer metastases

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Authors: Azza H. El-Medany, Hanan H. Hagar, Jamila H. El-Medany

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Ulcerative colitis (UC) is one of chronic inflammatory diseases primarily affecting colon with unknown etiology. Some researches papers mentioned the possibility of the use of drugs that affect the angiotensin II in reducing the complication of ulcerative colitis. The aim of the present study is to evaluate the potential protective and therapeutic effects of captopril and valsartan on ulcerative colitis induced experimentally in rats using acetic acid. The results were assessed by histological assessment of colonic tissues and measurement of malondialdehyde (MDA), tumor necrosis factor (TNF-α), transforming growth factor (TGF-1B), angiotensin converting enzyme (ACE), reduced glutathione (GSH) and platelet activating factor (PAF) levels in colonic tissues. Oral pre-treatment with captopril or valsartan in a dose of 30 mgkg-1 body weight for 2 weeks before induction of colitis (prophylactic groups) and continuously for 2 weeks after induction (therapeutic groups) significantly reduce MDA, TNF-α, PAF, TGF-1B and ACE levels in colonic tissues as compared to acetic acid control group. Also, a significant increase in GSH level was observed in colonic tissues. Captopril and valsartan attenuated the macroscopic and microscopic colonic damage induced by acetic acid. These results suggest that either captopril or valsartan may be effective as prophylactic or treatment of UC through inhibition of ACE and scavenging effect on oxygen-derived free radicals.

Keywords: captopril, valsartan, angiotensin converting enzyme, reduced glutathione, tumor necrosis factor

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Authors: Michio Kurosu

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Alterations in glycosylation not only directly impact cell growth and survival but also facilitate tumor-induced immunomodulation and eventual metastasis. Identification of cell type-specific glycoconjugates (tumor markers) has led to the discovery of new assay systems for certain cancers via immunodetection reagents. N- and O-linked glycans are the most abundant forms of glycoproteins. Recent studies of cancer immunotherapy are based on the immunogenicity of truncated O-glycan chains (e.g., Tn, sTn, T, and sLea/x). The prevalence of N-linked glycan changes in the development of tumor cells is known; however, therapeutic antibodies against N-glycans have not yet been developed. This is due to the lack of specificity of N-linked glycans between normal/healthy and cancer cells. Abnormal branching of N-linked glycans has been observed, particularly in solid cancer cells. While the discovery of drug-like glycosyltransferase inhibitors that block the biosynthesis of specific branching has a very low likelihood of success, altered glycosylation levels can be exploited by suppressing N-glycan biosynthesis through the inhibition of dolichyl-phosphate N-acetylglucosaminephosphotransferase1 (DPAGT1) activity. Inhibition of DPAGT1 function leads to changes of O-glycosylation on proteins associated with mitochondria and zinc finger binding proteins (indirect effects). On the basis of dynamic crosstalk between DPAGT1 and Snail/Slung/ZEB1 (a family of transcription factors that promote the repression of the adhesion molecules), we have developed pharmacologically acceptable selective DPAGT1 inhibitors. Tunicamycin kills a wide range of cancer and healthy cells in a non-selective manner. In sharp contrast, our DPAGT1 inhibitors display strong cytostatic effects against 16 solid cancers, which require the overexpression of DPAGT1 in their progression but do not affect the cell viability of healthy cells. The identified DPAGT1 inhibitors possess impressive anti-metastatic ability in various solid cancer cell lines and induce their mitochondrial structural changes, resulting in apoptosis. A prototype DPAGT1 inhibitor, APPB has already been proven to shrink solid tumors (e.g., pancreatic cancers, triple-negative breast cancers) in vivo while suppressing metastases and has strong synergistic effects when combined with current cytotoxic drugs (e.g., paclitaxel). At this conference, our discovery of selective DPAGT1 inhibitors with drug-like properties and proof-of-pharmaceutical concept studies of a novel DPAGT1 inhibitor are presented.

Keywords: DPAGT1 inhibitors, anti-metastatic drugs, natural product based drug designs, cytostatic effects

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Authors: Kamila Duś-Szachniewicz, Kinga M. Walaszek, Paweł Skiba, Paweł Kołodziej, Piotr Ziółkowski

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Cell adhesion is of fundamental importance in the cell communication, signaling, and motility, and its dysfunction occurs prevalently during cancer progression. The knowledge of the molecular and cellular processes involved in abnormalities in cancer cells adhesion has greatly increased, and it has been focused mainly on cellular adhesion molecules (CAMs) and tumor microenvironment. Unfortunately, most of the data regarding CAMs expression relates to study on cells maintained in standard oxygen condition of 21%, while the emerging evidence suggests that culturing cells in ambient air is far from physiological. In fact, oxygen in human tissues ranges from 1 to 11%. The aim of this study was to compare the effects of physiological lymph node normoxia (5% O2), and hyperoxia (21% O2) on the expression of cellular adhesion molecules of primary diffuse large B-cell lymphoma cells (DLBCL) isolated from 10 lymphoma patients. Quantitative RT-PCR and immunohistochemistry were used to confirm the differential expression of several CAMs, including ICAM, CD83, CD81, CD44, depending on the level of oxygen. Our findings also suggest that DLBCL cells maintained at ambient O2 (21%) exhibit reduced growth rate and migration ability compared to the cells growing in normoxia conditions. Taking into account all the observations, we emphasize the need to identify the optimal human cell culture conditions mimicking the physiological aspects of tumor growth and differentiation.

Keywords: adhesion molecules, diffuse large B-cell lymphoma, physiological normoxia, quantitative RT-PCR

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Authors: Rama Bhargava, Surabhi Nishad

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The infusion of nanofluids has dramatically enhanced the heat-carrying capacity of the fluids, applicable to many engineering and medical process where the temperature below freezing is required. Cryosurgery is an efficient therapy for the treatment of cancer, but sometimes the excessive cooling may harm the nearby healthy cells. Efforts are therefore done to develop a model which can cause to generate the low temperature as required. In the present study, a mathematical model is developed based on the bioheat transfer equation to simulate the heat transfer from the probe on a tumor (with irregular domain) using the hybrid technique consisting of element free Galerkin method with αα-family of approximation. The probe is loaded will nano-particles. The effects of different nanoparticles, namely Al₂O₃, Fe₃O₄, Au on the heat-producing rate, is obtained. It is observed that the temperature can be brought to (60°C)-(-30°C) at a faster freezing rate on the infusion of different nanoparticles. Besides increasing the freezing rate, the volume of the nanoparticle can also control the size and growth of ice crystals formed during the freezing process. The study is also made to find the time required to achieve the desired temperature. The problem is further extended for multi tumors of different shapes and sizes. The irregular shape of the frozen domain and the direction of ice growth are very sensitive issues, posing a challenge for simulation. The Meshfree method has been one of the accurate methods in such problems as a domain is naturally irregular. The discretization is done using the nodes only. MLS approximation is taken in order to generate the shape functions. Sufficiently accurate results are obtained.

Keywords: cryosurgery, EFGM, hybrid, nanoparticles

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Authors: Rafia S. Al-lamki, Jun Wang, Simon Pacey, Jordan Pober, John R. Bradley

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Tumor necrosis factor alpha (TNF), signaling through TNFR2, may act an autocrine growth factor for renal tubular epithelial cells. Clear cell renal carcinomas (ccRCC) contain cancer stem cells (CSCs) that give rise to progeny which form the bulk of the tumor. CSCs are rarely in cell cycle and, as non-proliferating cells, resist most chemotherapeutic agents. Thus, recurrence after chemotherapy may result from the survival of CSCs. Therapeutic targeting of both CSCs and the more differentiated bulk tumor populations may provide a more effective strategy for treatment of RCC. In this study, we hypothesized that TNFR2 signaling will induce CSCs in ccRCC to enter cell cycle so that treatment with ligands that engage TNFR2 will render CSCs susceptible to chemotherapy. To test this hypothesis, we have utilized wild-type TNF (wtTNF) or specific muteins selective for TNFR1 (R1TNF) or TNFR2 (R2TNF) to treat either short-term organ cultures of ccRCC and adjacent normal kidney (NK) tissue or cultures of CD133+ cells isolated from ccRCC and adjacent NK, hereafter referred to as stem cell-like cells (SCLCs). The effect of cyclophosphamide (CP), currently an effective anticancer agent, was tested on CD133+SCLCs from ccRCC and NK before and after R2TNF treatment. Responses to TNF were assessed by flow cytometry (FACS), immunofluorescence, and quantitative real-time PCR, TUNEL, and cell viability assays. Cytotoxic effect of CP was analyzed by Annexin V and propidium iodide staining with FACS. In addition, we assessed the effect of TNF on isolated SCLCs differentiation using a three-dimensional (3D) culture system. Clinical samples of ccRCC contain a greater number SCLCs compared to NK and the number of SCSC increases with higher tumor grade. Isolated SCLCs show expression of stemness markers (oct4, Nanog, Sox2, Lin28) but not differentiation markers (cytokeratin, CD31, CD45, and EpCAM). In ccRCC organ cultures, wtTNF and R2TNF increase CD133 and TNFR2 expression and promote cell cycle entry whereas wtTNF and R1TNF increase TNFR1 expression and promote cell death of SCLCs. Similar findings are observed in SCLCs isolated from NK but the effect was greater in SCLCs isolated from ccRCC. Application of CP distinctly triggered apoptotic and necrotic cell death in SLCSs pre-treatment with R2TNF as compared to CP treatment alone, with SCLCs from ccRCC more sensitive to CP compared to SLCS from NK. Furthermore, TNF promotes differentiation of SCLCs to an epithelial phenotype in 3D cultures, confirmed by cytokeratin expression and loss of stemness markers Nanog and Sox2. The differentiated cells show positive expression of TNF and TNFR2. These findings provide evidence that selective engagement of TNFR2 drive CSCs to cell proliferation/differentiation, and targeting of cycling cells with TNFR2 agonist in combination with anti-cancer agents may be a potential therapy for RCC.

Keywords: cancer stem cells, ccRCC, cell cycle, cell death, TNF, TNFR1, TNFR2, CD133

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Authors: Mrinal Kanti Bhowmik, Kakali Das Jr., Barin Kumar De, Debotosh Bhattacharjee

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Breast cancer is the most common cancer and a leading cause of death for women in the 35 to 55 age group. Early detection of breast cancer can decrease the mortality rate of breast cancer. Mammography is considered as a ‘Gold Standard’ for breast cancer detection and a very popular modality, presently used for breast cancer screening and detection. The screening of digital mammograms often leads to over diagnosis and a consequence to unnecessary traumatic & painful biopsies. For that reason recent studies involving the use of thermal imaging as a screening technique have generated a growing interest especially in cases where the mammography is limited, as in young patients who have dense breast tissue. Tumor is a significant sign of breast cancer in both mammography and thermography. The tumors are complex in structure and they also exhibit a different statistical and textural features compared to the breast background tissue. Fractal geometry is a geometry which is used to describe this type of complex structure as per their main characteristic, where traditional Euclidean geometry fails. Over the last few years, fractal geometrics have been applied mostly in many medical image (1D, 2D, or 3D) analysis applications. In breast cancer detection using digital mammogram images, also it plays a significant role. Fractal is also used in thermography for early detection of the masses using the thermal texture. This paper presents an overview of the recent aspects and initiatives of fractals in breast cancer detection in both mammography and thermography. The scope of fractal geometry in automatic breast cancer detection using digital mammogram and thermogram images are analysed, which forms a foundation for further study on application of fractal geometry in medical imaging for improving the efficiency of automatic detection.

Keywords: fractal, tumor, thermography, mammography

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Authors: Yasmin M. Attia, Hanan S. El-Abhar, Mahmoud M. Al Marzabani, Samia A. Shouman

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Background: Tamoxifen (TAM) is the most commonly used hormone therapy for the treatment of early and metastatic breast cancer. Although it significantly decreases the tumor recurrence rate and provides an overall benefit, as much as 20–30% of women still relapse during or after long-term therapy. 3-Bromopyruvate (3-BP) is a promising agent with impressive antitumor effects in several models of animal tumors and cell lines. Aim: This study was designed to investigate the combined effect of (TAM) and (3-BP) in breast cancer cells and to explore their molecular interaction via assessment of apoptotic, angiogenic, and metastatic markers. Methods: In vitro cytotoxicity study was carried out for both compounds to determine the combination regimen producing a synergistic effect and mechanistic pathways were studied using RT-PCR and western techniques. Moreover, the anti-oncolytic and anti-angiogenic potentials were assessed in mice bearing solid Ehrlich carcinoma (SEC). Results: The combined treatment significantly increased the expressions and protein levels of caspase 7, 9, and 3 and decreased of angiogenic markers VEGF, HIF-1α, and HK2 compared to cells treated with either drug individually. However, there were no significant changes in MMP-2 and MMP-9 protein levels. Interestingly, the in vivo results supported the in vitro findings; there was a decrease in the tumor volume and VEFG using immunohistochemistry in the combination-treated groups compared to either TAM or 3-BP treated one. Conclusion: 3-BP synergizes the cytotoxic effect of TAM by increasing apoptosis and decreasing angiogenesis which makes this combination a promising regimen to be applied clinically.

Keywords: tamoxifen, 3-bromopyruvate, breast cancer, cytotoxicity, angiogenesis

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Authors: Javier Enciso-Benavides, Fredy Fabian, Carlos Castaneda, Luis Alfaro, Alex Choque, Aparicio Aguilar, Javier Enciso

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Background: The use of biomarkers in breast cancer diagnosis, therapy, and prognosis has gained increasing interest. Cancer stem cells (CSCs) are a subpopulation of tumor cells that can drive tumor initiation and may cause relapse. Therefore, due to the importance of diagnosis, therapy, and prognosis, several biomarkers that characterize CSCs have been identified; however, in treatment-naïve triple-negative breast tumors, there is an urgent need to identify new biomarkers and therapeutic targets. According to this, the aim of this study was to identify serum proteins associated with cancer stem cells and pluripotency in women with triple-negative breast tumors in order to subsequently identify a biomarker for this type of breast tumor. Material and Methods: Whole blood samples from 12 women with histopathologically diagnosed triple-negative breast tumors were used after obtaining informed consent from the patient. Blood serum was obtained by conventional procedure and frozen at -80ºC. Identification of cancer stem cell-associated proteins was performed by matrix-assisted laser desorption/ionisation-assisted laser desorption/ionisation mass spectrometry (MALDI-TOF MS), protein analysis was obtained using the AB Sciex TOF/TOF™ 5800 system (AB Sciex, USA). Sequences not aligned by ProteinPilot™ software were analyzed by Protein BLAST. Results: The following proteins related to pluripotency and cancer stem cells were identified by MALDI TOF/TOF mass spectrometry: A-chain, Serpin A12 [Homo sapiens], AIEBP [Homo sapiens], Alpha-one antitrypsin, AT {internal fragment} [human, partial peptide, 20 aa] [Homo sapiens], collagen alpha 1 chain precursor variant [Homo sapiens], retinoblastoma-associated protein variant [Homo sapiens], insulin receptor, CRA_c isoform [Homo sapiens], Hydroxyisourate hydrolase [Streptomyces scopuliridis], MUCIN-6 [Macaca mulatta], Alpha-actinin-3 [Chrysochloris asiatica], Polyprotein M, CRA_d isoform, partial [Homo sapiens], Transcription factor SOX-12 [Homo sapiens]. Recommendations: The serum proteins identified in this study should be investigated in the exosome of triple-negative breast cancer stem cells and in the blood serum of women without breast cancer. Subsequently, proteins found only in the blood serum of women with triple-negative breast cancer should be identified in situ in triple-negative breast cancer tissue in order to identify a biomarker to study the evolution of this type of cancer, or that could be a therapeutic target. Conclusions: Eleven cancer stem cell-related serum proteins were identified in 12 women with triple-negative breast cancer, of which MUCIN-6, retinoblastoma-associated protein variant, transcription factor SOX-12, and collagen alpha 1 chain are the most representative and have not been studied so far in this type of breast tumor. Acknowledgement: This work was supported by Proyecto CONCYTEC–Banco Mundial “Mejoramiento y Ampliacion de los Servicios del Sistema Nacional de Ciencia Tecnología e Innovacion Tecnologica” 8682-PE (104-2018-FONDECYT-BM-IADT-AV).

Keywords: triple-negative breast cancer, MALDI TOF/TOF MS, serum proteins, cancer stem cells

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