Search results for: cancer stem cell (CSC)

Authors: Kapoor Anurag, Sharma Pradeep, Mittal K Kailash, Kumar Ajai, Jawad Kalbe, Amit Kumar Singh

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Background: Oral squamous cell carcinoma (OSCC) is the most prevalent malignant tumour on a global scale. Limited research has been conducted on tumour markers in oral cancer, and additional evaluation is required for several tumour producers that show clinical promise. The present study aimed to find out the co-relation of β-2 Microglobulin and Lipid Bound Sialic Acid in oral carcinoma patients. Methodology: The present case-control study was carried out on 35 patients with histopathologically confirmed OSCC and 35 age-matched controls. Serum concentrations of 2-Microglobulin and Total Sialic Acid (TSA) in the participants were determined via ELISA and spectrophotometric technique, respectively. Results: The OSCC group consisted of 20 males and 15 females, with an average age of 58 years, while the control group comprised 18 males and 17 females, with an average age of 55 years. Elevated levels of β2-microglobulin (3.87±0.12) and LSA (73.57±2.42) were observed in OSCC patients compared to controls (2.25±0.18; 65.21±2.06, respectively). Further examination based on smoking status revealed a significant increase in both β2-microglobulin and LSA levels among smokers compared to non-smokers (p < 0.05). Conclusion: The study suggests a notable association between higher levels of β2-microglobulin and LSA in oral squamous cell carcinoma (OSCC) patients who smoke compared to non-smokers. This observation leads to a hypothesis that this disparity could potentially serve as a significant contributing factor to the advancement of oral cancer.

Keywords: biochemistry human cancer, human, oral carcinoma, marker

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Authors: Peramachi Sathiyamoorthy, Jacop Gopas, Avi Golan Goldhirsh

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Corchorus olitorius is a leafy vegetable and an industrial crop. The herb has antioxidant, anti inflammatory, and anti-cancer properties. To assay the pharmaceutical properties, aqueous extracts of leaves and seeds from C. olitorius were tested against drug resistant melanoma cell line. The test showed LC50 of the extract was 0.08µg/ml. Aqueous seed extract exhibited higher melanoma inhibiting activity than leaf extract. Dialysis of seed extract showed that the active compound is less than 12 KDa. The compound with <3 KDa MW separated by microconcentration of seed extract showed 70.5 % inhibition of melanoma cell growth. Among the two fractions obtained by Gel filtration with G10 column, the first fraction at 1:2000 dilutions exhibited 100% inhibition of melanoma growth. The compound with Rf value 0.86 (MA4) isolated by TLC separation showed about 98% cytotoxicity against melanoma at 1: 1000 dilutions. Furthermore, HPLC separation of MA4 compound with Superdex 75 column resulted in 4 compounds. Out of 4, one compound showed melanoma inhibition. The active compound is identified by reagent methods as Strophanthidin. Further toxicological and clinical studies will lead to the development of a potential drug to treat drug resistant melanoma.

Keywords: corchorus olitorius, melanoma, drug development, strophanthidin

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Authors: A. Alao Olumuyiwa

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Health hazards reported to be associated with exposure to electromagnetic radiations which include brain tumors, genotoxic effects, neurological effects, immune system deregulation, allergic responses and some cardiovascular effects are discussed under a closed tabular model in this study. This review however showed that there is strong and robust evidence that chronic exposures to electromagnetic frequency across the spectrum, through strength, consistency, biological plausibility and many dose-response relationships, may result in brain cancer and other carcinogenic disease symptoms. There is therefore no safe threshold because of the genotoxic nature of the mechanism that may however be involved. The discussed study explains that the cell phone has induced effects upon the blood –brain barrier permeability and the cerebellum exposure to continuous long hours RF radiation may result in significant increase in albumin extravasations. A physical Biomodeling approach is however employed to review this health effects using Specific Absorption Rate (SAR) of different GSM machines to critically examine the symptoms such as a decreased loco motor activity, increased grooming and reduced memory functions in a variety of animal spices in classified grouped and sub grouped models.

Keywords: brain cancer, electromagnetic radiations, physical biomodeling, specific absorption rate (SAR)

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Authors: Debasmita Mukhopadhyay, Manika Pal Bhadra

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MiRNAs contribute to oncogenesis either as tumor suppressors or oncogenes. Hence, discovery of miRNA-based therapeutics are imperative to ameliorate cancer. Modulation of miRNA maturation is accomplished via several therapeutic agents, including small molecules and oligonucleotides. Due to the attractive pharmacokinetic properties of small molecules over oligonucleotides, we set to identify small molecule inhibitors of a metastasis-inducing microRNA. Cytotoxicity profile of aza-flavanone C1 was analyzed in a panel of breast cancer cells employing the NCI-60 screen protocols. Flow cytometry, immunofluorescence and western blotting of apoptotic or EMT markers were performed to analyze the effect of C1. A dual luciferase assay unequivocally suggested that C1 repressed endogenous miR-10b in MDA-MB-231 cells. A derivative of aza-flavanone C1 is shown as a strong inhibitor miR-10b. Blockade of miR-10b by C1 resulted in decreased expression of miR-10b targets in an aggressive breast cancer cell line model, MDA-MB-231. Abrogation of TWIST1, an EMT-inducing transcription factor also contributed to C1 mediated apoptosis. Moreover C1 exhibited a specific and selective down-regulation of miR-10b and did not function as a general inhibitor of miRNA biogenesis or other oncomiRs of breast carcinoma. Aza-flavanone congener C1 functions as a potent inhibitor of the metastasis-inducing microRNA, miR-10b. Our present study provides evidence for targeting metastasis-inducing microRNA, miR-10b with a derivative of Aza-flavanone. Better pharmacokinetic properties of small molecules place them as attractive agents compared to nucleic acids based therapies to target miRNA. Further work, in generating analogues based on aza-flavanone moieties will significantly improve the affinity of the small molecules to bind miR-10b. Finally, it is imperative to develop small molecules as novel miRNA-therapeutics in the fight against cancer.

Keywords: breast cancer, microRNA, metastasis, EMT

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Authors: Omar Youssef, Aija Knuuttila, Paivi Piirilä, Virinder Sarhadi, Sakari Knuutila

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Exhaled breath condensate (EBC) is a unique sample that allows studying different genetic changes in lung carcinoma through a non-invasive way. With the aid of next generation sequencing (NGS) technology, analysis of genetic mutations has been more efficient with increased sensitivity for detection of genetic variants. In order to investigate the possibility of applying this method for cancer diagnostics, mutations in EBC DNA from lung cancer patients and healthy individuals were studied by using NGS. The key aim is to assess the feasibility of using this approach to detect clinically important mutations in EBC. EBC was collected from 20 healthy individuals and 9 lung cancer patients (four lung adenocarcinomas, four 8 squamous cell carcinoma, and one case of mesothelioma). Mutations in hotpot regions of 22 genes were studied by using Ampliseq Colon and Lung cancer panel and sequenced on Ion PGM. Results demonstrated that all nine patients showed a total of 19 cosmic mutations in APC, BRAF, EGFR, ERBB4, FBXW7, FGFR1, KRAS, MAP2K1, NRAS, PIK3CA, PTEN, RET, SMAD4, and TP53. In controls, 15 individuals showed 35 cosmic mutations in BRAF, CTNNB1, DDR2, EGFR, ERBB2, FBXW7, FGFR3, KRAS, MET, NOTCH1, NRAS, PIK3CA, PTEN, SMAD4, and TP53. Additionally, 45 novel mutations not reported previously were also seen in patients’ samples, and 106 novel mutations were seen in controls’ specimens. KRAS exon 2 mutations G12D was identified in one control specimen with mutant allele fraction of 6.8%, while KRAS G13D mutation seen in one patient sample showed mutant allele fraction of 17%. These findings illustrate that hotspot mutations are present in DNA from EBC of both cancer patients and healthy controls. As some of the cosmic mutations were seen in controls too, no firm conclusion can be drawn on the clinical importance of cosmic mutations in patients. Mutations reported in controls could represent early neoplastic changes or normal homeostatic process of apoptosis occurring in lung tissue to get rid of mutant cells. At the same time, mutations detected in patients might represent a non-invasive easily accessible way for early cancer detection. Follow up of individuals with important cancer mutations is necessary to clarify the significance of these mutations in both healthy individuals and cancer patients.

Keywords: exhaled breath condensate, lung cancer, mutations, next generation sequencing

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Authors: Safa Safdar

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Breast cancer is a type of cancer which is developed by the formation of a tumor on the breast. This tumor invades and causes different electrolyte imbalance. The present study was designed to measure the serum calcium and inorganic phosphorous levels and to check the frequency of hypercalcemia and hypophosphatemia in breast cancer patients. Serum calcium and phosphorous levels of fifty breast cancer women of 18-70 years of age group and fifty healthy women of same age group were measured by using semi-automated chemistry analyzer ( Humalyzer 3000, Human, Germany ). Significant variation in these levels was observed. The mean calcium value in BC patients was higher 9.398 mg/dl as compared to controls which were 8.694 mg/dl. Whereas the mean value of inorganic phosphorus level was lower 4.060 mg/dl in BC patients as compared to controls having 4.456 mg/dl. In this study, the frequency of hypercalcemia in Breast cancer patients was 10% i.e. only 10 out of 50 Breast cancer patients were suffering from hypercalcemia. Whereas the frequency of hypophosphatemia in this study was only 2 % i.e. only 1 out of 50 patients was suffering from hypophosphatemia. Thus it is concluded that there is a significant change in serum calcium and inorganic phosphorous levels in Breast cancer patients as the disease progresses. So, this study will be helpful for the clinicians to maintain serum calcium and phosphorous levels in Breast cancer patients and also preventing them from further complications.

Keywords: serum analysis, calcium, inorganic phosphorus, hpercalcemia hypophosphatemia

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Authors: Razvan Mercut, Mihaela Ionescu, Vlad Parvanescu, Razvan Ghita, Tudor-Gabriel Caragea, Cristina Simionescu, Marius-Eugen Ciurea

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Introduction: Over the past years, the incidence of non-melanoma skin cancer (NMSC) has continuously increased, being one of the most commonly diagnosed carcinomasofthe cephalic extremity. NMSC regroups basal cell carcinoma (BCC), squamous cell carcinoma (SCC), Merkel cell carcinoma, cutaneous lymphoma, and sarcoma. The most common forms are BCC and SCC, both still implying a significant level of morbidity due to local invasion (especially BCC), even if the overall death rates are declining. The objective of our study was the evaluation of clinical and histological aspects of NMSC for a group of patients with BCC and SCC, from Craiova, a south-western major city in Romania. Materialand method: Our study lot comprised 65 patients, with an almost equal distribution of sexes, and ages between 23-91 years old (mean value±standard deviation62.61±16.67), all treated within the Clinic of Plastic Surgery and Reconstructive Microsurgery, Clinical Emergency County Hospital Craiova, Romania, between 2019-2020. In order to determine the main morphological characteristics of both studied cancers, we used paraffin embedding techniques, with various staining methods:hematoxylin-eosin, Masson's trichrome stain with aniline blue, and Periodic acid-schiffAlcian Blue. The statistical study was completed using Microsoft Excel (Microsoft Corp., Redmond, WA, USA), with XLSTAT (Addinsoft SARL, Paris, France). Results: The overall results of our study indicate that BCC accounts for 67.69% of all NMSC forms; SCC covers 27.69%, while 4.62% are representedby other forms. The most frequent site is the nose for BCC (27.69%, 18 patients), being followed by preauricular regions, forehead, and periorbital areas. For patients with SCC, tumors were mainly located at lips level (66.67%, 12 patients). The analysis of NMSC histological forms indicated that nodular BCC is predominant (45.45%, 20 patients), as well as ulcero-vegetant SCC (38.89%, 7 patients). We have not identified any topographic characteristics or NMSC forms significantly related to age or sex. Conclusions: The most frequent NMSC form identified for our study lot was BCC. The preferred location was the nose for BCC. For SCC, the oral cavity is the most frequent anatomical site, especially the lips level. Nodular BCC and ulcero-vegetant SCC were the most commonly identified histological types. Our findings emphasize the need for periodic screening, in order to improve prevention and early treatment for these malignancies.

Keywords: non-melanoma skin cancer, basal cell carcinoma, squamous cell carcinoma, histological

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Authors: Naser Shagerdi Esmaeli, Mohsen Hamidpour

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Purposes: The activation of coagulation in patients with cancer contributes significantly to morbidity and mortality rates and may play a fundamental role in the host response to growing tumor’s. Patients with cancer are clearly at high risk for the development of venous thromboembolism (VTE), particularly during chemotherapy and surgery. This situation is aggravated by the use of venous access catheters and possibly growth factors. Methods: Data derived from large, randomized, controlled trials have been used to determine the true incidence of this complication of cancer and its treatment. The incidence based on the analyses of these randomized controlled trials varies from 1% for limited stage patients with breast cancer treated with tamoxifen to 60% for patients with any type of cancer who are subjected to orthopedic surgery and do not receive prophylactic therapy. Results: In view of the morbidity and mortality attributable to VTE in cancer, widespread utilization of prophylactic anticoagulation therapy, which has proven safe and effective in a variety of situations, should be considered. While migratory thrombophlebitis is a clear indicator of an underlying neoplasm, the risk of cancer in patients with the more typical form of VTE has been the subject of intense debate over recent years. Conclusion: Some investigators have suggested that the relative risk of being diagnosed with occult cancer within six months of an episode of VTE (particularly recurrent VTE) could be up to 10-fold. However, the cost-effectiveness of aggressive screening for cancer in patients with VTE has not yet been defined adequately.

Keywords: venous thromboembolism, malignancy, cancer, tumor, heparin

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Authors: Kamini Kaushal

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Medicinal plants of Ayurveda are effective in the treatment of cervical cancer. The aim of this paper is to assess anti cancerous activities of these medicinal plants against cancer. Most of the medicinal plants in Ayurveda are using to treat cervical cancer as name of disease as treatment of YONI VYAPADA. The selected plants has been studied scientifically in India and evidence based written since Vedic era. The compilation results showed potential anti cervical cancer activity of the tested plants. There plants are remaining under the dark due to lack of awareness, lack of popularity and barrier of language. Now this is the time to eye opener regarding the classical text and clinical evidences, so that we can give the hope to world's affected women from this disease. World is waiting for such type of remedy which is having zero side effects, low cost and effective.

Keywords: anti cancerous, cervical cancer, ayurveda, medicinal plants, scientific study, classical text

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Authors: G. Tamilpavai, C. Vishnuppriya

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Studying DNA (deoxyribonucleic acid) sequence is useful in biological processes and it is applied in the fields such as diagnostic and forensic research. DNA is the hereditary information in human and almost all other organisms. It is passed to their generations. Earlier stage detection of defective DNA sequence may lead to many developments in the field of Bioinformatics. Nowadays various tedious techniques are used to identify defective DNA. The proposed work is to analyze and identify the cancer-causing DNA motif in a given sequence. Initially the human DNA sequence is separated as k-mers using k-mer separation rule. The separated k-mers are clustered using Self Organizing Map (SOM). Using Levenshtein distance measure, cancer associated DNA motif is identified from the k-mer clusters. Experimental results of this work indicate the presence or absence of cancer causing DNA motif. If the cancer associated DNA motif is found in DNA, it is declared as the cancer disease causing DNA sequence. Otherwise the input human DNA is declared as normal sequence. Finally, elapsed time is calculated for finding the presence of cancer causing DNA motif using clustering formation. It is compared with normal process of finding cancer causing DNA motif. Locating cancer associated motif is easier in cluster formation process than the other one. The proposed work will be an initiative aid for finding genetic disease related research.

Keywords: bioinformatics, cancer motif, DNA, k-mers, Levenshtein distance, SOM

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Authors: Olais A. Ingrid, Peraza G. Leydi, Estrella C. Damaris

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Breast cancer is the most common among women worldwide; the different treatments can bring sequels that directly affect the quality of life, such as lymphedema. The objective was to determine if there is presence of lymphedema secondary to breast cancer in Yucatecan women. It was an observational, analytical, cross-sectional study, 92 women were included who met the following criteria: women with surgical treatment for unilateral: breast cancer, aged between 25 and 65 years old, minimum 6 weeks after unilateral breast surgery and have completed any type of chemotherapy or adjuvant radiotherapy treatment for breast cancer. The evaluation was through indirect measurement volume by circometry to determine the presence of lymphedema. 23% of women had lymphedema grade I. It related to the presence of some of the symptoms like stiffness, swelling, decreased range of motion and feeling of heaviness in the arm of the operated side of the breast. It is important to determine the presence of lymphedema to perform physical therapy treatment.

Keywords: breast cancer, lymphedema, physical therapy, Yucatan

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Authors: D. ChobfroushKhoei, S. K. Heidari , Sh. Dariadel

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Carbon nanotubes were used in medical sciences especially in drug delivery system and cancer therapy. In this study, we functionalized carboxylated single-wall carbon nanotubes (SWNT-COOH) with 2-en 4-hydroxy cyclo 1-octanon. Synthesized sample was characterized by FT-IR, Raman spectroscopy, SEM, TGA and cellular investigations. The results showed well formation of SWNT-Ester. Cell viability assay results and microscopic observations demonstrated that cancerous cells were killed in the sample. The synthesized sample can be used as a toxic material for cancer therapy.

Keywords: MWNT-COOH, functionalization, phenylisocyanate, phenylisothiocyanate, 1, 4-phenylendiamine, toxicity investigation

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Authors: Segen Asayehegn

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Introduction: In Tigray, Ethiopia, next to cervical cancer, breast cancer is one of the most common cancer health problems for women. Objectives: This article is proposed to identify the prospective and potential risk factors affecting the time-to-first-recurrence of breast cancer patients in Tigray, Ethiopia. Methods: The data were taken from the patient’s medical record that registered from January 2010 to January 2020. The study considered a sample size of 1842 breast cancer patients. Powerful non-parametric and parametric shared frailty survival regression models (FSRM) were applied, and model comparisons were performed. Results: Out of 1842 breast cancer patients, about 1290 (70.02%) recovered/cured the disease. The median cure time from breast cancer is found at 12.8 months. The model comparison suggested that the lognormal parametric shared a frailty survival regression model predicted that treatment, stage of breast cancer, smoking habit, and marital status significantly affects the first recurrence of breast cancer. Conclusion: Factors like treatment, stages of cancer, and marital status were improved while smoking habits worsened the time to cure breast cancer. Recommendation: Thus, the authors recommend reducing breast cancer health problems, the regional health sector facilities need to be improved. More importantly, concerned bodies and medical doctors should emphasize the identified factors during treatment. Furthermore, general awareness programs should be given to the community on the identified factors.

Keywords: acceleration factor, breast cancer, Ethiopia, shared frailty survival models, Tigray

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Authors: Ling-Ling E., Hong-Chen Liu, Dong-Sheng Wang, Fang Su, Xia Wu, Zhan-Ping Shi, Yan Lv, Jia-Zhu Wang

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Objective: The objective of the present study is to evaluate the capacity of a tissue-engineered bone complex of recombinant human bone morphogenetic protein 2 (rhBMP-2) mediated dental pulp stem cells (DPSCs) and nano-hydroxyapatite/collagen/poly(L-lactide)(nHAC/PLA) to reconstruct critical-size alveolar bone defects in New Zealand rabbit. Methods: Autologous DPSCs were isolated from rabbit dental pulp tissue and expanded ex vivo to enrich DPSCs numbers, and then their attachment and differentiation capability were evaluated when cultured on the culture plate or nHAC/PLA. The alveolar bone defects were treated with nHAC/PLA, nHAC/PLA+rhBMP-2, nHAC/PLA+DPSCs, nHAC/PLA+DPSCs+rhBMP-2, and autogenous bone (AB) obtained from iliac bone or were left untreated as a control. X-ray and a polychrome sequential fluorescent labeling were performed post-operatively and the animals were sacrificed 12 weeks after operation for histological observation and histomorphometric analysis. Results: Our results showed that DPSCs expressed STRO-1 and vementin, and favoured osteogenesis and adipogenesis in conditioned media. DPSCs attached and spread well, and retained their osteogenic phenotypes on nHAC/PLA. The rhBMP-2 could significantly increase protein content, alkaline phosphatase (ALP) activity/protein, osteocalcin (OCN) content, and mineral formation of DPSCs cultured on nHAC/PLA. The X-ray graph, the fluorescent, histological observation and histomorphometric analysis showed that the nHAC/PLA+DPSCs+rhBMP-2 tissue-engineered bone complex had an earlier mineralization and more bone formation inside the scaffold than nHAC/PLA, nHAC/PLA+rhBMP-2 and nHAC/PLA+DPSCs, or even autologous bone. Implanted DPSCs contribution to new bone were detected through transfected eGFP genes. Conclutions: Our findings indicated that stem cells existed in adult rabbit dental pulp tissue. The rhBMP-2 promoted osteogenic capability of DPSCs as a potential cell source for periodontal bone regeneration. The nHAC/PLA could serve as a good scaffold for autologous DPSCs seeding, proliferation and differentiation. The tissue-engineered bone complex with nHAC/PLA, rhBMP-2, and autologous DPSCs might be a better alternative to autologous bone for the clinical reconstruction of periodontal bone defects.

Keywords: nano-hydroxyapatite/collagen/poly (L-lactide), dental pulp stem cell, recombinant human bone morphogenetic protein, bone tissue engineering, alveolar bone

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Authors: Zoe Goldberger, Priscilla S. Briquez, Jeffrey A. Hubbell

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Tumor cells have mutations resulting from genetic instability that the immune system can actively recognize. Immune checkpoint immunotherapy (ICI) is commonly used in the clinic to re-activate immune reactions against mutated proteins, called neoantigens, resulting in tumor remission in cancer patients. However, only around 20% of patients show durable response to ICI. While tumor mutational burden (TMB) has been approved by the Food and Drug Administration (FDA) as a criterion for ICI therapy, the relevance of the subcellular localizations of the mutated proteins within the tumor cell has not been investigated. Here, we hypothesized that localization of mutations impacts the effect of immune responsiveness to ICI. We analyzed publicly available tumor mutation sequencing data of ICI treated patients from 3 independent datasets. We extracted the subcellular localization from the UniProtKB/Swiss-Prot database and quantified the proportion of membrane, cytoplasmic, nuclear, or secreted mutations per patient. We analyzed this information in relation to response to ICI treatment and overall survival of patients showing with 1722 ICI-treated patients that high mutational burden localized at the membrane (mTMB), correlate with ICI responsiveness, and improved overall survival in multiple cancer types. We anticipate that our results will ameliorate predictability of cancer patient response to ICI with potential implications in clinical guidelines to tailor ICI treatment. This would not only increase patient survival for those receiving ICI, but also patients’ quality of life by reducing the number of patients enduring non-effective ICI treatments.

Keywords: cancer, immunotherapy, membrane neoantigens, efficacy prediction, biomarkers

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Authors: Tatsiana Ihnatovich, Darya Nizheharodava, Mikalai Halabarodzka, Tatsiana Savitskaya, Marina Zafranskaya

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Liver fibrosis is a complex of histological changes resulting from chronic liver disease accompanied by an excessive production and deposition of extracellular matrix components in the hepatic parenchyma. Liver fibrosis is a serious medical and social problem. Hepatic stellate cells (HSCs) make a significant contribution to the extracellular matrix deposition due to liver injury. Mesenchymal stem cells (MSCs) have a pronounced anti-inflammatory, regenerative and immunomodulatory effect; they are able to differentiate into hepatocytes and induce apoptosis of activated HSCs that opens the prospect of their use for preventing the excessive fibro-formation and the development of liver cirrhosis. The aim of the study is to evaluate the effect of MSCs therapy on the expression of fibrogenesis markers genes in liver tissue and HSCs cultures of rats with experimental liver cirrhosis (ELC). Materials and methods: ELC was induced by the common bile duct ligation (CBDL) in female Wistar rats (n = 19) with an average body weight of 250 (220 ÷ 270) g. Animals from the control group (n = 10) were sham-operated. On the 56th day after the CBDL, the rats of the experimental (n = 12) and the control (n = 5) groups received intraportal MSCs in concentration of 1×106 cells/animal (previously obtained from rat’s bone marrow) or saline, respectively. The animals were taken out of the experiment on the 21st day. HSCs were isolated by sequential liver perfusion in situ with following disaggregation, enzymatic treatment and centrifugation of cell suspension on a two-stage density gradient. The expression of collagen type I (Col1a1) and type III (Col3a1), matrix metalloproteinase type 2 (MMP2) and type 9 (MMP9), tissue inhibitor of matrix metalloproteinases type 1 (TIMP1), transforming growth factor β type 1 (TGFβ1) and type 3 (TGFβ3) was determined by real-time polymerase chain reaction. Statistical analysis was performed using Statistica 10.0. Results: In ELC rats compared to sham-operated animals, a significant increase of all studied markers expression was observed. The administration of MSCs led to a significant decrease of all detectable markers in the experimental group compared to rats without cell therapy. In ELC rats, an increased MMP9/TIMP1 ratio after cell therapy was also detected. The infusion of MSCs in the sham-operated animals did not lead to any changes. In the HSCs from ELC animals, the expression of Col1a1 and Col3a1 exceeded the similar parameters of the control group (p <0.05) and statistically decreased after the MSCs administration. The correlation between Col3a1 (Rs = 0.51, p <0.05), TGFβ1 (Rs = 0.6, p <0.01), and TGFβ3 (Rs = 0.75, p <0.001) expression in HSCs cultures and liver tissue has been found. Conclusion: Intraportal administration of MSCs to rats with ELC leads to a decreased Col1a1 and Col3a1, MMP2 and MMP9, TIMP1, TGFβ1 and TGFβ3 expression. The correlation between the expression of Col3a1, TGFβ1 and TGFβ3 in liver tissue and in HSCs cultures indicates the involvement of activated HSCs in the fibrogenesis that allows considering HSCs to be the main cell therapy target in ELC.

Keywords: cell therapy, experimental liver cirrhosis, hepatic stellate cells, mesenchymal stem cells

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Authors: Pakize Neslihan Taslı, Alev Cumbul, Gul Merve Yalcın, Fikrettin Sahin

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A key experimental trial in the regeneration of large oral and craniofacial defects is the neogenesis of osseous and ligamentous interfacial structures. Currently, oral regenerative medicine strategies are unpredictable for repair of tooth supporting tissues destroyed as a consequence of trauma, chronic infection or surgical resection. A different approach combining the gel-casting method with Hydroxy Apatite HA-based scaffold and different cell lineages as a hybrid system leads to successively mimic the early stage of tooth development, in vitro. HA is widely accepted as a bioactive material for guided bone and tooth regeneration. In this study, it was reported that, HA porous scaffold preparation, characterization and evaluation of structural and chemical properties. HA is the main factor that exists in tooth and it is in harmony with structural, biological, and mechanical characteristics. Here, this study shows mimicking immature tooth at the late bell stage design and construction of HA scaffolds for cell transplantation of human Adipose Stem Cells (hASCs), human Bone Marrow Stem Cells (hBMSCs) and Gingival Epitelial cells for the formation of human tooth dentin-pulp-enamel complexes in vitro. Scaffold characterization was demonstrated by SEM, FTIR and pore size and density measurements. The biological contraction of dental tissues against each other was demonstrated by mRNA gene expressions, histopatologic observations and protein release profile by ELISA tecnique. The tooth shaped constructs with a pore size ranging from 150 to 300 µm arranged by gathering right amounts of materials provide interconnected macro-porous structure. The newly formed tissue like structures that grow and integrate within the HA designed constructs forming tooth cementum like tissue, pulp and bone structures. These findings are important as they emphasize the potential biological effect of the hybrid scaffold system. In conclusion, this in vitro study clearly demonstrates that designed 3D scaffolds shaped as a immature tooth at the late bell stage were essential to form enamel-dentin-pulp interfaces with an appropriate cell and biodegradable material combination. The biomimetic architecture achieved here is providing a promising platform for dental tissue engineering.

Keywords: tooth regeneration, tissue engineering, adipose stem cells, hydroxyapatite tooth engineering, porous scaffold

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Authors: Ahmad Jawad Fardin

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Over 60% of patients with breast cancer in Afghanistan present late with advanced stage III and IV, a major cause for the poor survival rate. The objectives of this study were to identify the contributing factors for the diagnosis and treatment delay and its outcome. This cross-sectional study was conducted on 318 patients with histologically confirmed breast cancer in the oncology department of Jamhoriat hospital, which is the first and only national cancer center in Afghanistan; data were collected from medical records and interviews conducted with women diagnosed with breast cancer, linear regression and logistic regression were used for analysis. Patient delay was defined as the time from first recognition of symptoms until first medical consultation and doctor form first consultation with a health care provider until histological confirmation of breast cancer. The mean age of patients was 49.2+_ 11.5years. The average time for the final diagnosis of breast cancer was 8.5 months; most patients had ductal carcinoma 260.7 (82%). Factors associated with delay were low education level 76% poor socioeconomic and cultural conditions 81% lack of cancer center 73% lack of screening 19%. The stage distribution was as follows stage IV 4 22% stage III 44.4% stage II 29.3% stage I 4.3%. Complex associated factors were identified to delayed the diagnosis of breast cancer and increased adverse outcomes consequently. Raising awareness and education in women, the establishment of cancer centers and providing accessible diagnosis service and screening, training of general practitioners; required to promote early detection, diagnosis and treatment.

Keywords: delayed diagnosis and poor outcome, breast cancer in Afghanistan, poor outcome of delayed breast cancer treatment, breast cancer delayed diagnosis and treatment in Afghanistan

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Authors: Soodabeh Shahid Sales, Azam Rastgar Moghadam, Mehrane Mehramiz, Malihe Entezari, Kazem Anvari, Mohammad Sadegh Khorrami, Saeideh Ahmadi Simab, Ali Moradi, Seyed Mahdi Hassanian, Majid Ghayour-Mobarhan, Gordon A. Ferns, Amir Avan

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Background Esophageal cancer has been reported as the eighth most common cancer universal and the seventh cause of cancer-related death in men .recent studies have revealed that cytochrome P450, family 1, subfamily B, polypeptide 1, which plays a role in metabolizing xenobiotics, is associated with different cancers. Therefore in the present study, we investigated the impact of CYP1B1-rs1056836 on esophagus squamous cell carcinoma (ESCC) patients. Method: 317 subjects, with and without ESCC were recruited. DNA was extracted and genotyped via Real-time PCR-Based Taq Man. Kaplan Meier curves were utilized to assess overall and progression-free survival. To evaluate the relationship between patients clinicopathological data, genotypic frequencies, disease prognosis, and patients survival, Pearson chi-square and t-test were used. Logistic regression was utilized to assess the association between the risk of ESCC and genotypes. Results: the genotypic frequency for GG, GC, and CC are respectively 58.6% , 29.8%, 11.5% in the healthy group and 51.8%, 36.14% and 12% in ESCC group. With respect to the recessive genetic inheritance model, an association between the GG genotype and stage of ESCC were found. Also, statistically significant results were not found for this variation and risk of ESCC. Patients with GG genotype had a decreased risk of nodal metastasis in comparison with patients with CC/CG genotype, although this link was not statistically significant. Conclusion: Our findings illustrated the correlation of CYP1B1-rs1056836 as a potential biomarker for ESCC patients, supporting further studies in larger populations in different ethnic groups. Moreover, further investigations are warranted to evaluate the association of emerging marker with dietary intake and lifestyle.

Keywords: Cytochrome P450, esophagus squamous cell carcinoma, dietary intake, lifestyle

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Authors: Roman Matejka, Vaclav Prochazka, Tibor Izak, Jana Stepanovska, Martina Travnickova, Alexander Kromka

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Cell-based impedance spectroscopy is suitable method for electrical monitoring of cell activity especially on substrates that cannot be easily inspected by optical microscope (without fluorescent markers) like decellularized tissues, nano-fibrous scaffold etc. Special sensor for this measurement was developed. This sensor consists of corning glass substrate with gold interdigitated electrodes covered with diamond layer. This diamond layer provides biocompatible non-conductive surface for cells. Also, a special PPFC flow cultivation chamber was developed. This chamber is able to fix sensor in place. The spring contacts are connecting sensor pads with external measuring device. Construction allows real-time live cell imaging. Combining with perfusion system allows medium circulation and generating shear stress stimulation. Experimental evaluation consist of several setups, including pure sensor without any coating and also collagen and fibrin coating was done. The Adipose derived stem cells (ASC) and Human umbilical vein endothelial cells (HUVEC) were seeded onto sensor in cultivation chamber. Then the chamber was installed into microscope system for live-cell imaging. The impedance measurement was utilized by vector impedance analyzer. The measured range was from 10 Hz to 40 kHz. These impedance measurements were correlated with live-cell microscopic imaging and immunofluorescent staining. Data analysis of measured signals showed response to cell adhesion of substrates, their proliferation and also change after shear stress stimulation which are important parameters during cultivation. Further experiments plan to use decellularized tissue as scaffold fixed on sensor. This kind of impedance sensor can provide feedback about cell culture conditions on opaque surfaces and scaffolds that can be used in tissue engineering in development artificial prostheses. This work was supported by the Ministry of Health, grants No. 15-29153A and 15-33018A.

Keywords: bio-impedance measuring, bioreactor, cell cultivation, diamond layer, gold interdigitated electrodes, tissue engineering

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Authors: Odunayo Christy Atewolara-Odule, Olapeju O. Aiyelaagbe

Abstract:

The search for new natural anti-oxidants has grown tremendously over the years because reactive oxygen species (ROS) production and oxidative stress have been linked to a large number of human degenerative diseases, such as cancer, cardiovascular diseases, inflammation, and diabetes. Tapinanthus bangwensis, a parasitic plant commonly known as mistletoe belonging to the Loranthaceae family, is mostly employed traditionally to treat inflammation, cancer, diabetes, and hypertension to mention a few. In this study, air-dried pulverized leaves and stem of Tapinanthus bangwensis were successively extracted with n-hexane, ethyl acetate, and methanol to give the corresponding crude extracts. The extracts were purified by column chromatography and high-performance liquid chromatography to give the isolated compounds. Structural elucidation was done using mass spectrometry, Fourier transform infra-red, 1D and 2D NMR spectroscopy. The antioxidant activity of the compounds was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ascorbic acid as standard. Three compounds; Friedelin, Eudesmic acid (3,4,5-trimethoxybenzoic) and Methyl-3,4,5-trimethoxybenzoate were isolated from the extracts of Tapinanthus bangwensis. Friedelin was isolated from the ethyl acetate extract of the stem while the two other compounds were isolated from the methanol extract of the leaves. The percentages of free radical scavenging activities of the compounds are as follows: Friedelin, 73.69%, methyl-3,4,5-trimethoxybenzoate, 79.33% and eudesmic, 87.68% anti-oxidant activity which were quite comparable to 93.96% given by ascorbic acid. We are reporting, to our best knowledge, for the first time the occurrence of friedelin and eudesmic acid in Tapinanthus bangwensis. The high anti-oxidant activity of these compounds supports the use of this plant in the management of diabetes and hypertension as they will be useful in combating complications arising from the disease.

Keywords: column chromatography, eudesmic acid, friedelin, Tapinanthus bangwensis

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Authors: Pamita Awasthi, Kirna, Shilpa Dogra, Manu Vatsal, Ritu Barthwal

Abstract:

Doxorubicin, also known as adriamycin, is an anthracycline class of drug used in cancer chemotherapy. It is used in the treatment of non-Hodgkin’s lymphoma, multiple myeloma, acute leukemias, breast cancer, lung cancer, endometrium cancer and ovary cancers. It functions via intercalating DNA and ultimately killing cancer cells. The major side effects of doxorubicin are hair loss, myelosuppression, nausea & vomiting, oesophagitis, diarrhoea, heart damage and liver dysfunction. The minor modifications in the structure of compound exhibit large variation in the biological activity, has prompted us to carry out the synthesis of sulfonamide derivatives. Sulfonamide is an important feature with broad spectrum of biological activity such as antiviral, antifungal, diuretics, anti-inflammatory, antibacterial and anticancer activities. Structure of the synthesized compound N-(1-methyl-2-oxo-2-N-methyl anilino-ethyl)benzene sulfonamide confirmed by proton nuclear magnetic resonance (1H NMR),13C NMR, Mass and FTIR spectroscopic tools to assure the position of all protons and hence stereochemistry of the molecule. Further we have reported the binding potential of synthesized sulfonamide analogues in comparison to doxorubicin drug using Auto Dock 4.2 software. Computational binding energy (B.E.) and inhibitory constant (Ki) has been evaluated for the synthesized compound in comparison of doxorubicin against Poly (dA-dT).Poly (dA-dT) and Poly (dG-dC).Poly (dG-dC) sequences. The in vitro cytotoxic study against human breast cancer cell lines confirms the better anticancer activity of the synthesized compound over currently in use anticancer drug doxorubicin. The IC50 value of the synthesized compound is 7.12 µM where as for doxorubicin is 7.2 µ.

Keywords: Doxorubicin, auto dock, in silco, in vitro

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Authors: Jefunnie Matahum, Yu-Chi Kuo, Chao-Ming Su, Tzong-Rong Ger

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Magnetic cell labeling is of great importance in various applications in biomedical fields such as cell separation and cell sorting. Since analytical methods for quantification of cell uptake of magnetic nanoparticles (MNPs) are already well established, image analysis on single cell level still needs more characterization. This study reports an alternative non-destructive quantification methods of single-cell uptake of positively charged MNPs. Magnetophoresis experiments were performed to calculate the number of MNPs in a single cell. Mobility of magnetic cells and the area of intracellular MNP stained by Prussian blue were quantified by image processing software. ICP-MS experiments were also performed to confirm the internalization of MNPs to cells. Initial results showed that the magnetic cells incubated at 100 µg and 50 µg MNPs/mL concentration move at 18.3 and 16.7 µm/sec, respectively. There is also an increasing trend in the number and area of intracellular MNP with increasing concentration. These results could be useful in assessing the nanoparticle uptake in a single cell level.

Keywords: magnetic nanoparticles, single cell, magnetophoresis, image analysis

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Authors: Maomao Cao

Abstract:

Background and aims While the association between higher consumption of fish and lower liver cancer risk has been confirmed, however, the association between specific fish intake and liver cancer risk remains unknown. We aimed to identify the association between specific fish consumption and the risk of liver cancer. Methods: Based on a community-based seropositive hepatitis B cohort involving 18404 individuals, face to face interview was conducted by a standardized questionnaire to acquire baseline information. Three common fish types in this study were analyzed, including freshwater fish, sea fish, and small fish (shrimp, crab, conch, and shell). All participants received liver cancer screening, and possible cases were identified by CT or MRI. Multivariable logistic models were applied to estimate the odds ratio (OR) and 95% confidence intervals (CI). Multivariate multiple imputations were utilized to impute observations with missing values. Results: 179 liver cancer cases were identified. Consumption of freshwater fish and sea fish at least once a week had a strong inverse association with liver cancer risk compared with the lowest intake level, with an adjusted OR of 0.53 (95% CI, 0.38-0.75) and 0.38 (95% CI, 0.19-0.73), respectively. This inverse association was also observed after the imputation. There was no statistically significant association between intake of small fish and liver cancer risk (OR=0.58, 95%, CI 0.32-1.08). Conclusions: Our findings suggest that consumption of freshwater fish and sea fish at least once a week could reduce liver cancer risk.

Keywords: cross-sectional study, fish intake, liver cancer, risk factor

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Authors: H. M. Imam, H. M. Rezk, A. F. Tohamy

Abstract:

Background: Human umbilical cord blood (HUCB) is considered as a unique source for stem cells. HUCB contain different types of progenitor cells which could differentiate into hepatocytes. Aims: To investigate the potential of rat's liver damage repair using human umbilical cord mesenchymal stem cells (hUCMSCs). We investigated the feasibility for hUCMSCs in recovery from liver damage. Moreover, investigating fibrotic liver repair and using the CCl4-induced model for liver damage in the rat. Methods: Rats were injected with 0.5 ml/kg CCl4 to induce liver damage and progressive liver fibrosis. hUCMSCs were injected into the rats through the tail vein; Stem cells were transplanted at a dose of 1×106 cells/rat after 72 hours of CCl4 injection without receiving any immunosuppressant. After (6 and 8 weeks) of transplantation, blood samples were collected to assess liver functions (ALT, AST, GGT and ALB) and level of Procollagen III as a liver fibrosis marker. In addition, hepatic tissue regeneration was assessed histopathologically and immunohistochemically using antihuman monoclonal antibodies against CD34, CK19 and albumin. Results: Biochemical and histopathological analysis showed significantly increased recovery from liver damage in the transplanted group. In addition, HUCB stem cells transdifferentiated into functional hepatocytes in rats with hepatic injury which results in improving liver structure and function. Conclusion: Our findings suggest that transplantation of hUCMSCs may be a novel therapeutic approach for treating liver fibrosis. Therefore, hUCMSCs are a potential option for treatment of liver cirrhosis.

Keywords: carbon tetra chloride, liver fibrosis, mesenchymal stem cells, rat

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Authors: M. A. Islam, P. J. Hazell, J. P. Escobedo, M. Saadatfar

Abstract:

Quasistatic compression and micro structural characterization of closed cell aluminium foams of different pore size and cell distributions has been carried out. Metallic foams have good potential for lightweight structures for impact and blast mitigation and therefore it is important to find out the optimized foam structure (i.e. cell size, shape, relative density, and distribution) to maximize energy absorption. In this paper, we present results for two different aluminium metal foams of density 0.5 g/cc and 0.7 g/cc respectively that have been tested in quasi-static compression. The influence of cell geometry and cell topology on quasistatic compression behavior has been investigated using computed tomography (micro-CT) analysis. The compression behavior and micro structural characterization will be presented.

Keywords: metal foams, micro-CT, cell topology, quasistatic compression

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Authors: Jamboor K. Vishwanatha

Abstract:

Among the potent anti-cancer agents, curcumin has been found to be very efficacious against various cancer cells. Despite multiple medicinal benefits of curcumin, poor water solubility, poor physiochemical properties and low bioavailability continue to pose major challenges in developing a formulation for clinical efficacy. To improve its potential application in the clinical area, we formulated poly lactic-co-glycolic acid (PLGA) nanoparticles. The PLGA nanoparticles were formulated using solid-oil/water emulsion solvent evaporation method and then characterized for percent yield, encapsulation efficiency, surface morphology, particle size, drug distribution within nanoparticles and drug polymer interaction. Our studies showed the successful formation of smooth and spherical curcumin loaded PLGA nanoparticles with a high percent yield of about 92.01±0.13% and an encapsulation efficiency of 90.88±0.14%. The mean particle size of the nanoparticles was found to be 145nm. The in vitro drug release profile showed 55-60% drug release from the nanoparticles over a period of 24 hours with continued sustained release over a period of 8 days. Exposure to curcumin loaded nanoparticles resulted in reduced cell viability of cancer cells compared to normal cells. We used a novel non-covalent insertion of a homo-bifunctional spacer for targeted delivery of curcumin to various cancer cells. Functionalized nanoparticles for antibody/targeting agent conjugation was prepared using a cross-linking ligand, bis(sulfosuccinimidyl) suberate (BS3), which has reactive carboxyl group to conjugate efficiently to the primary amino groups of the targeting agents. In our studies, we demonstrated successful conjugation of antibodies, Annexin A2 or prostate specific membrane antigen (PSMA), to curcumin loaded PLGA nanoparticles for targeting to prostate and breast cancer cells. The percent antibody attachment to PLGA nanoparticles was found to be 92.8%. Efficient intra-cellular uptake of the targeted nanoparticles was observed in the cancer cells. These results have emphasized the potential of our multifunctional curcumin nanoparticles to improve the clinical efficacy of curcumin therapy in patients with cancer.

Keywords: polymeric nanoparticles, cancer therapy, sustained release, curcumin

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Authors: Mohammad Syahirin Aisha, Khairul Imran Sainan

Abstract:

The PEM fuel cell is a device that generate electric by electrochemical reaction between hydrogen fuel and oxygen in the fuel cell stack. PEM fuel cell consists of an anode (hydrogen supply), a cathode (oxygen supply) and an electrolyte that allow charges move between the two positions of the fuel cell. The only product being developed after the reaction is water (H2O) and heat as the waste which does not emit greenhouse gasses. The performance of fuel cell affected by numerous parameters. This study is restricted to cathode parameters that affect fuel cell performance. At the anode side, the reactant is not going through any changes. Experiments with variation in air velocity (3m/s, 6m/s and 9m/s), temperature (10oC, 20oC, 35oC) and relative humidity (50%, 60%, and 70%) have been carried out. The experiments results are presented in the form of fuel cell stack power output over time, which demonstrate the impacts of the various air condition on the execution of the PEM fuel cell. In this study, the experimental analysis shows that with variation of air conditions, it gives different fuel cell performance behavior. The maximum power output of the experiment was measured at an ambient temperature of 25oC with relative humidity and 9m/s velocity of air.

Keywords: air-breathing PEM fuel cell, cathode side, performance, variation in air condition

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Authors: Hatice Kahyaoglu Sut, Serap Unsar, Seda Kurt

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The aim of this study is to investigate sexual quality of life in women with gynecological cancer. This cross-sectional study was conducted on 37 women with gynecological cancer and 39 control women (in menopausal term) at the Gynecooncology and Menopause Clinics of Trakya University Medical Faculty between January and July 2015. Women who had sexual active and willing to participate in the study filled an information form inquiring socio-demographic characteristics and Sexual Quality of Life Questionnaire-Female (SQLQ-F). Data were analyzed by Mann-Whitney-U test and Kruskal-Wallis test. The average age of the women was 52.7 ± 7.6 (51.2 ± 8.7 in women with gynecological cancer, 54.3 ± 6.0 in controls). The SQOL-F scores in women with gynecologic cancer (60.8 ± 22.4) was lower than controls (63.5 ± 20.7), however, there was no statistically significant difference (p = 0.759). Women with gynecological cancer who had vaginal dryness and pain during sexual intercourse (45.7 ± 21.3) were lower SQOL-F total score than control group (66.0 ± 21.7) (p = 0.014). The SQOL-F scores in women who took chemotherapy treatment (55.7 ± 17.8) were lower than in women who had not chemotherapy treatment (86.8 ± 16.6) (p = 0.005). In conclusion, taking chemotherapy treatment and occurring vaginal dryness and pain complaints during sexual intercourse in women with gynecological cancer reduces sexual quality of life. Therefore, sexual quality of life in women with gynecological cancer should be evaluated, and they should be supported in order to improve their sexual quality of life.

Keywords: gynecological cancer, quality of life, sexuality, women

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Authors: Arefeh Jafarian, Mohammad Taghikani, Saied Abroun, Amir Allahverdi, Masoud Soleimani

Abstract:

Introduction: The miRNAs have key roles in control of pancreatic islet development and insulin secretion. In this regards, current study investigated the pancreatic differentiation of human bone marrow mesenchymal stem cells (hBM-MSCs) by up-regulation of miR-375 and down-regulation of miR-9 by lentiviruses containing miR-375 and anti-miR-9. Findings: After 21 days of induction, islet-like clusters containing insulin producing cells (IPCs) were confirmed by dithizone (DTZ) staining. The IPCs and β cell specific related genes and proteins were detected using qRT-PCR and immunofluorescence on days 7, 14 and 21 of differentiation. Glucose challenge test was performed at different concentrations of glucose as well as extracellular and intracellular insulin and C-peptide were assayed using ELISA kit. In derived IPCs by miR-375 alone are capable to express insulin and other endocrine specific transcription factors, the cells lack the machinery to respond to glucose. The differentiated hMSCs by miR-375 and anti-miR-9 lentiviruses could secrete insulin and c-peptide in a glucose-regulated manner. Conclusion: It was found that over-expression of miR-375 led to a reduction in levels of Mtpn protein in derived IPCs, while treatment with anti-miR-9 following miR-375 over-expression had synergistic effects on MSCs differentiation and insulin secretion in a glucose-regulated manner. The researchers reported that silencing of miR-9 increased OC-2 protein in IPCs that may contribute to the observed glucose-regulated insulin secretion. These findings highlight miRNAs functions in stem cells differentiation and suggest that they could be used as therapeutic tools for gene-based therapy in diabetes mellitus.

Keywords: diabetes, differentiation, MSCs, insulin producing cells, miR-375, miR-9

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