Search results for: breast cancer resistance protein

Authors: Hawon Lee, Young-Pil Kim

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Visualizing matrix metalloproteinases (MMPs) activity is necessary for understanding cancer metastasis because they are implicated in cell migration and invasion by degrading the extracellular matrix (ECM). While much effort has been made to sense the MMP activity, but extracellularly long-term monitoring of MMP activity still remains challenging. Here, we report a collagen-bound fluorescent bioprobe for the detection of MMP-2 activity in the extracellular environment. This bioprobe consists of ECM-immobilized part (including collagen-bound protein) and MMP-sensing part (including peptide substrate linked with fluorescence resonance energy transfer (FRET) coupler between donor green fluorescent protein (GFP) and acceptor TAMRA dye), which was constructed through intein-mediated self-splicing conjugation. Upon being immobilized on the collagen-coated surface, this bioprobe enabled efficient long-lasting observation of MMP-2 activity in the cultured cells without affecting cell growth and viability. As a result, the FRET ratio (acceptor/donor) decreased as the MMP2 activity increased in cultured cancer cells. Furthermore, unlike wild-type MMP-2, mutated MMP-2 expression (Y580A in the hemopexin region) gave rise to lowering the secretion of MMP-2 in HeLa. Conclusively, our method is anticipated to find applications for tracing and visualizing enzyme activity.

Keywords: collagen, ECM, FRET, MMP

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Authors: Asghar Arif

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Lung cancer has been recognized as one of the greatest common cancers, causing the annual mortality rate of about 1.2 million people in the world. Lung cancer is the most prevalent cancer in men and the third-most common cancer among women (after breast and digestive cancers).Recent evidences have shown the inflammatory process as one of the potential factors of cancer. Tuberculosis (TB), pneumonia, and chronic bronchitis are among the most important inflammation-inducing factors in the lungs, among which TB has a more profound role in the emergence of cancer.TB is one of the important mortality factors throughout the world, and 205,000 death cases are reported annually due to this disease. Chronic inflammation and fibrosis due to TB can induce genetic mutation and alternations. Parenchyma tissue of lung is involved in both diseases of TB and lung cancer, and continuous cough in lung cancer, morphological vascular variations, lymphocytosis processes, and generation of immune system mediators such as interleukins, are all among the factors leading to the hypothesis regarding the role of TB in lung cancer Some reports have shown that the induction of necrosis and apoptosis or TB reactivation, especially in patients with immune-deficiency, may result in increasing IL-17 and TNF_α, which will either decrease P53 activity or increase the expression of Bcl-2, decrease Bax-T, and cause the inhibition of caspase-3 expression due to decreasing the expression of mitochondria cytochrome oxidase. It has been also indicated that following the injection of BCG vaccine, the host immune system will be reinforced, and in particular, the rates of gamma interferon, nitric oxide, and interleukin-2 are increased. Therefore, CD4 + lymphocyte function will be improved, and the person will be immune against cancer.Numerous prospective studies have so far been conducted on the role of TB in lung cancer, and it seems that this disease is effective in that particular cancer.One of the main challenges of lung cancer is its correct and timely diagnosis. Unfortunately, clinical symptoms (such as continuous cough, hemoptysis, weight loss, fever, chest pain, dyspnea, and loss of appetite) and radiological images are similar in TB and lung cancer. Therefore, anti-TB drugs are routinely prescribed for the patients in the countries with high prevalence of TB, like Pakistan. Regarding the similarity in clinical symptoms and radiological findings of lung cancer, proper diagnosis is necessary for TB and respiratory infections due to nontuberculousmycobacteria (NTM). Some of the drug resistive TB cases are, in fact, lung cancer or NTM lung infections. Acid-fast staining and histological study of phlegm and bronchial washing, culturing and polymerase chain reaction TB are among the most important solutions for differential diagnosis of these diseases. Briefly, it is assumed that TB is one of the risk factors for cancer. Numerous studies have been conducted in this regard throughout the world, and it has been observed that there is a significant relationship between previous TB infection and lung cancer. However, to prove this hypothesis, further and more extensive studies are required. In addition, as the clinical symptoms and radiological findings of TB, lung cancer, and non-TB mycobacteria lung infections are similar, they can be misdiagnosed as TB.

Keywords: TB and lung cancer, TB people, TB servivers, TB and HIV aids

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Authors: Sweta Pandey, Samridhi Dhyani, Susmita Chaudhuri

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Klebsiella pneumoniae causes a wide range of infections, including urinary tract infections, sepsis, bacteremia, pneumonia, and liver abscesses. The emergence of multi-drug resistance in this bacterium led to a major setback for clinical management. WHO also endorsed a need for finding alternative therapy to antibiotics for the treatment of these infections. Development of vaccines and passive antibody therapy has been proven as a potent alternative to antibiotics in the case of MDR, XDR, and PDR Klebsiella infections. Siderophore receptors have been demonstrated to be overexpressed for the internalization of iron siderophore complexes during infections in most Gram-negative bacteria. For the present study, immune response to siderophore receptors to establish this protein as a potential immunogen for the development of therapeutic leads was explored. Clinical strains of Klebsiella pneumoniae were grown in iron-deficient conditions, and the iron-regulated outer membrane proteins were extracted and characterized through mass spectrometry for specific identification. The gene for identified protein was cloned in pET- 28a vector and expressed in E. coli. The native protein and the recombinant protein were isolated and purified and used as antigens for the generation of immune response in BALB/c mice. The native protein of Klebsiella pneumoniae grown in iron-deficient conditions was identified as FepA (Ferrienterobactin receptor) and other siderophore receptors. This 80 kDa protein generated an immune response in BALB/c mice. The antiserum from mice after subsequent booster doses was collected and showed binding with FepA protein in western blot and phagocytic uptake of the K. pneumoniae in the presence antiserum from immunized mice also observed from the animal studies after bacterial challenge post immunisation in mice have shown bacterial clearance. The antiserum from mice showed binding and clearance of the Klebsiella pneumoniae bacteria in vitro and in vivo. These antigens used for generating an active immune response in mice can further be used for therapeutic monoclonal antibody development against Klebsiella pneumoniae infections.

Keywords: antiserum, FepA, Klebsiella pneumoniae, multi drug resistance, siderophore receptor

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Authors: Mubita Namuyamba

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Despite an increase in the number of cancer programs and partnerships in cancer care provision, the burden of cancer in Zambia is increasingly having a significant impact on morbidity and mortality rates. The increase in cancer morbidity and mortality rates has given rise to psychological and psycho social implications (PPsI) in cancer care. Cancer patients, care givers and health care providers are faced with a multitude of PPsIs in cancer care that mainly impact negatively on the management of cancer patients. The study adopted a case study design and was purposively conducted at the Cancer Diseases Hospital in Lusaka (Zambia) after obtaining ethical clearance from the Ethics committee. The sample for this study included 70 cancer patients, 20 care givers and 5 hospital staff (4 nurses and 1 doctor). Data was collected using interviews guides, focus group discussion guides and questionnaires respectively. The qualitative data was analysed thematically. The various psychological and psychosocial challenges that conspire to deter the provision of effective cancer care nursing and improved methods of minimizing the psychological and psychosocial implications in cancer care are the products of this study.

Keywords: case study, enquiry, psychological and psycho social aspects, Zambia

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Authors: Guido Trautmann-Sáez, Mario Pérez-Won, Vilbett Briones, María José Bugueño, Gipsy Tabilo-Munizaga, Luis Gonzáles-Cavieres

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Shrimp by-products are a valuable source of protein. However, traditional protein extraction methods have limitations in terms of their efficiency. Protein extraction from shrimp (Pleuroncodes monodon) industrial by-products assisted with ohmic heating (OH), microwave (MW) and pulsed electric field (PEF). It was performed by chemical method (using NaOH and HCl 2M) assisted with OH, MW and PEF in a continuous flow system (5 ml/s). Protein determination, differential scanning calorimetry (DSC) and Fourier-transform infrared (FTIR). Results indicate a 19.25% (PEF) 3.65% (OH) and 28.19% (MW) improvement in protein extraction efficiency. The most efficient method was selected for the electrospinning process and obtaining fiber.

Keywords: electrospinning process, emerging technology, protein extraction, shrimp by-products

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Authors: Jyothi Nagraj, Sudeshna Mukherjee, Rajdeep Chowdhury

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Autophagy has recently been linked with cancer cell survival post drug insult contributing to acquisition of resistance. However, the molecular signaling governing autophagic survival response is poorly explored. In our study, in osteosarcoma (OS) cells cisplatin shock was found to activate both MAPK and autophagy signaling. An activation of JNK and autophagy acted as pro-survival strategy, while ERK1/2 triggered apoptotic signals upon cisplatin stress. An increased sensitivity of the cells to cisplatin was obtained with simultaneous inhibition of both autophagy and JNK pathway. Furthermore, we observed that the autophagic stimulation upon drug stress regulates other developmentally active signaling pathways like the Hippo pathway in OS cells. Cisplatin resistant cells were thereafter developed by repetitive drug exposure followed by clonal selection. Basal levels of autophagy were found to be high in resistant cells to. However, the signaling mechanism leading to autophagic up-regulation and its regulatory effect differed in OS cells upon attaining drug resistance. Our results provide valuable clues to regulatory dynamics of autophagy that can be considered for development of improved therapeutic strategy against resistant type cancers.

Keywords: JNK, autophagy, drug resistance, cancer

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Authors: Nandhakumar Elumalai, Purushothaman Ayyakannu, Sachidanandam T. Panchanatham

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Background: Understanding the basic mechanisms and factors underlying the tumor growth and invasion has gained attention in recent times. The processes of angiogenesis and apoptosis are known to play a vital role in various stages of cancer. The vascular endothelial growth factor (VEGF) is well established as one of the key regulators of tumor angiogenesis while MMPs are known for their exclusive ability to degrade ECM. Objective: The present study was designed to evaluate the pro apoptotic and anti angiogenic activity of the herbal formulation Shemamruthaa. The anticancer activity of Shemamruthaa was tested in breast cancer cell line (MCF-7). Results of MTT, trypan blue and flow cytometric analysis of apoptotis suggested that Shemamruthaa can induce cytotoxicity in cancer cells, in a concentration- and time dependent manner and induce apoptosis. With these results, we further evaluated the antiangiogenic and pro-apoptotic activities of Shemamruthaa in DMBA induced mammary carcinoma in Sprague Dawley rats. Flavono tumour was induced in 8-week-old Sprague-Dawley rats by gastric intubation of 25 mg DMBA in 1ml olive oil. After 90 days of induction period, the rats were orally administered with Shemamruthaa (400 mg/kg body wt) for 45 days. Treatment with the drug SM significantly modulated the expression of p53, MMP-2, MMP-3, MMP-9 and VEGF by means of its anti angiogenic and protease inhibiting activity. Conclusion: Based on these results, it might be concluded that the formulation, Shemamruthaa, constituted of dried flowers of Hibiscus rosa-sinensis, fruits of Emblica officinalis, and honey has been found to exhibit pronounced antiproliferative and apoptotic effects. This enhanced anticancer effect of Shemamruthaa might be attributed to the synergistic action of polyphenols such as flavonoids, tannins, alkaloids, glycosides, saponins, steroids, terpenoids, vitamin C, niacin, pyrogallol, hydroxymethylfurfural, trilinolein, and other compounds present in the formulation. Collectively, these results demonstrate that Shemamruthaa holds potential to be developed as a potent chemotherapeutic agent against mammary carcinoma.

Keywords: Shemamruthaa, flavonoids, MCF-7 cell line, mammary cancer

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Authors: Imran Ali

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General chemotherapy for cancer treatment has many side and toxic effects. A new approach of targeting nano anti-cancer drug is under development stage and only few drugs are available in the market today. The unique features of these drugs are targeted action on cancer cells only without any side effect. Sometimes, these are called magic drugs. The important molecules used for nano anti-cancer drugs are cisplatin, carboplatin, bleomycin, 5-fluorouracil, doxorubicin, dactinomycin, 6-mercaptopurine, paclitaxel, topotecan, vinblastin and etoposide etc. The most commonly used materials for preparing nano particles carriers are dendrimers, polymeric, liposomal, micelles inorganic, organic etc. The proposed lecture will comprise the-of-art of nano drugs in cancer chemo-therapy including preparation, types of drugs, mechanism, future perspectives etc.

Keywords: cancer, nano-anti-cancer drugs, chemo-therapy, mechanism of action, future perspectives

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Authors: Gulcin Yildiz, Hao Feng

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In recent years there is growing interested in using soy protein because of several advantages compared to other protein sources, such as high nutritional value, steady supply, and low cost. Soy protein isolate (SPI) is the most refined soy protein product. It contains 90% protein in a moisture-free form and has some desirable functionalities. Creating a protein-polysaccharide conjugate to be the emulsifying agent rather than the protein alone can markedly enhance its stability. This study was undertaken to examine the effects of ultrasound treatments on the physicochemical properties of SPI-starch conjugates. The soy protein isolate (SPI, Pro-Fam® 955) samples were obtained from the Archer Daniels Midland Company. Protein concentrations were analyzed by the Bardford method using BSA as the standard. The volume-weighted mean diameters D [4,3] of protein–polysaccharide conjugates were measured by dynamic light scattering (DLS). Surface hydrophobicity of the conjugates was measured by using 1-anilino-8-naphthalenesulfonate (ANS) (Sigma-Aldrich, St. Louis, MO, USA). Increasing the pH from 2 to 12 resulted in increased protein solubility. The highest solubility was 69.2% for the sample treated with ultrasonication at pH 12, while the lowest (9.13%) was observed in the Control. For the other pH conditions, the protein solubility values ranged from 40.53 to 49.65%. The ultrasound treatment significantly decreased the particle sizes of the SPI-modified starch conjugates. While the D [4,3] for the Control was 731.6 nm, it was 293.7 nm for the samples treated by sonication at pH 12. The surface hydrophobicity (H0) of SPI-starch at all pH conditions were significantly higher than those in the Control. Ultrasonication was proven to be effective in improving the solubility and emulsifying properties of soy protein isolate-starch conjugates.

Keywords: particle size, solubility, soy protein isolate, ultrasonication

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Authors: Muhammad S. Sajid, Asim Shamim, Muhammad Nisar Khan, Ashfaq A. Chatta, Muhammad Saqib

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Goats (Capra hircus) are a valued asset for resource poor farmers globally. But the parasitic infection especially Haemonchus contortus (Trichostrongylid), impact the health and production of goats globally. The present study intended to evaluate resilient and resistance to Haemonchus contortus in indigenous goat breeds (Teddy and Beetal) of Punjab, Pakistan. Out of 60, 30 goats of each breed were divided into 6 groups and each group contain five goats. Two group of each breed received challenged infection with 12000 and 18000 L3 (third stage) larvae of Haemonchus contortus under two infection protocol that is early and trickle and remaining two group of each breed was kept as control. Resilient and resistance of each breed was then measured on the basis of their phenotypic markers like: faecal egg counts, packed cell volume, FAMACHA score system, body weight, total protein, albumin and worm count on 2nd, 4th, 6th, and 8th week of post infection. Variation in response of each goat breeds to Haemonchus contortus was observed. Teddy breed showed significant (P < 0.05)resistance as compared to Beetal. It is probably first attempt to report an evaluation of goat breed response towards Haemonchus contortus in Pakistan. It was concluded that Teddy goats have a greater genetic tendency to resist against to the Haemonchus contortus infection and this breed could be kept and bred from the economic point of view. Evaluation of genetic markers are like: gene, protein expression, Immunoglobulin, Histamines and interleukins determination are recommended for future studies which can be helpful to be fined resistant breed of goats.

Keywords: goat, beetal, teddy, haemonchus contortus, resistance, resilience, phenotypic markers

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Authors: Yagahira E. Castro-Sesquen, Chloe Kim, Robert H. Gilman, David J. Sullivan, Peter C. Searson

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Diagnosis of severe malaria is particularly important in highly endemic regions since most patients are positive for parasitemia and treatment differs from non-severe malaria. Diagnosis can be challenging due to the prevalence of diseases with similar symptoms. Accurate diagnosis is increasingly important to avoid overprescribing antimalarial drugs, minimize drug resistance, and minimize costs. A nanoparticle-based assay for detection and quantification of Plasmodium falciparum histidine-rich protein 2 (HRP2) in urine and serum is reported. The assay uses magnetic beads conjugated with anti-HRP2 antibody for protein capture and concentration, and antibody-conjugated quantum dots for optical detection. Western Blot analysis demonstrated that magnetic beads allows the concentration of HRP2 protein in urine by 20-fold. The concentration effect was achieved because large volume of urine can be incubated with beads, and magnetic separation can be easily performed in minutes to isolate beads containing HRP2 protein. Magnetic beads and Quantum Dots 525 conjugated to anti-HRP2 antibodies allows the detection of low concentration of HRP2 protein (0.5 ng mL-1), and quantification in the range of 33 to 2,000 ng mL-1 corresponding to the range associated with non-severe to severe malaria. This assay can be easily adapted to a non-invasive point-of-care test for classification of severe malaria.

Keywords: HRP2 protein, malaria, magnetic beads, Quantum dots

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Authors: Dominika Pihikova, Stefan Belicky, Tomas Bertok, Roman Sokol, Petra Kubanikova, Jan Tkac

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Since aberrant glycosylation is frequently accompanied by both physiological and pathological processes in a human body (cancer, AIDS, inflammatory diseases, etc.), the analysis of tumor-associated glycan patterns have a great potential for the development of novel diagnostic approaches. Moreover, altered glycoforms may assist as a suitable tool for the specificity and sensitivity enhancement in early-stage prostate cancer diagnosis. In this paper we discuss the construction and optimization of ultrasensitive sandwich biosensor platform employing lectin as glycan-binding protein. We focus on the immunoassay development, reduction of non-specific interactions and final glycoprofiling of human serum samples including both prostate cancer (PCa) patients and healthy controls. The fabricated biosensor was measured by label-free electrochemical impedance spectroscopy (EIS) with further lectin microarray verification. Furthermore, we analyzed different biosensor interfaces with atomic force microscopy (AFM) in nanomechanical mapping mode showing a significant differences in the altitude. These preliminary results revealing an elevated content of α-2,3 linked sialic acid in PCa patients comparing with healthy controls. All these experiments are important step towards development of point-of-care devices and discovery of novel glyco-biomarkers applicable in cancer diagnosis.

Keywords: biosensor, glycan, lectin, prostate cancer

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Authors: Kristina Jansen, Maximilian Lennartz, Patrick Lebok, Guido Sauter, Ronald Simon, David Dum, Stefan Steurer

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DOG1 (Discovered on GIST1) is a voltage-gated calcium-activated chloride and bicarbonate channel that is highly expressed in interstitial cells of Cajal and in gastrointestinal stromal tumors (GIST) derived from Cajal cells. To systematically determine in what tumor entities and normal tissue types DOG1 may be further expressed, a tissue microarray (TMA) containing 15,965 samples from 121 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types were analyzed by immunohistochemistry. DOG1 immunostaining was found in 67 tumor types, including GIST (95.7%), esophageal squamous cell carcinoma (31.9%), pancreatic ductal adenocarcinoma (33.6%), adenocarcinoma of the Papilla Vateri (20%), squamous cell carcinoma of the vulva (15.8%) and the oral cavity (15.3%), mucinous ovarian cancer (15.3%), esophageal adenocarcinoma (12.5%), endometrioid endometrial cancer (12.1%), neuroendocrine carcinoma of the colon (11.1%) and diffuse gastric adenocarcinoma (11%). Low level-DOG1 immunostaining was seen in 17 additional tumor entities. DOG1 expression was unrelated to histopathological parameters of tumor aggressiveness and/or patient prognosis in cancers of the breast (n=1,002), urinary bladder (975), ovary (469), endometrium (173), stomach (233), and thyroid gland (512). High DOG1 expression was linked to estrogen receptor expression in breast cancer (p<0.0001) and the absence of HPV infection in squamous cell carcinomas (p=0.0008). In conclusion, our data identify several tumor entities that can show DOG1 expression levels at similar levels as in GIST. Although DOG1 is tightly linked to a diagnosis of GIST in spindle cell tumors, the differential diagnosis is much broader in DOG1 positive epithelioid neoplasms.

Keywords: biomarker, DOG1, immunohistochemistry, tissue microarray

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Authors: Shabnam Abdi, Behzad Toosi

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Background: Melanoma is the most lethal type of malignant skin cancer in humans and dogs since it spreads rapidly throughout the body. Despite significant advances in treatment, cancer at an advanced stage has a poor prognosis. Hence, more effective treatments are needed to enhance outcomes with fewer side effects. Erythropoietin-producing hepatocellular receptors are the largest family of receptor tyrosine kinases and are divided into two subfamilies, EphA and EphB, both of which play a significant role in disease, especially cancer. Due to their association with proliferation and invasion in many aggressive types of cancer, Eph receptor tyrosine kinases (Eph RTKs) are promising cancer therapy molecules. Because these receptors have not been studied in canine melanoma, we investigated how EphA2 influences survival and tumorigenicity of melanoma cells. Methods: Expression of EphA2 protein in canine melanoma cell lines and human melanoma cell line was evaluated by Western blot. Melanoma cells were transduced with lentiviral particles encoding Eph-targeting shRNAs or non-silencing shRNAs (control) for silencing the expression of EphA2 receptor, and silencing was confirmed by Western blotting and immunofluorescence. The effect of siRNA treatment on cellular proliferation, colony formation, tumorsphere assay, invasion was analyzed by Resazurin assay Matrigel invasion assay, respectively. Results: Expression of EphA2 was detected in canine and human melanoma cell lines. Moreover, stably silencing EphA2 by specific shRNAs significantly and consistently decreased the expression of EphA2 protein in both human and canine melanoma cells. Proliferation, colony formation, tumorsphere and invasion of melanoma cells were significantly decreased in EphA2 siRNA-treated cells compared to control. Conclusion: Our data provide the first functional evidence that the EphA2 receptor plays a critical role in the malignant cellular behavior of melanoma in both human and dogs.

Keywords: ephA2, targeting, melanoma, human, canine

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Authors: Shujun Xie, Shirong Zhang, Shenglin Ma

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Background: Chronic inflammation might lead to many malignancies, and inadequate resolution could play a crucial role in tumor invasion, progression, and metastases. A randomised, double-blind, placebo-controlled trial shows that IL-1β inhibition with canakinumab could reduce incident lung cancer and lung cancer mortality in patients with atherosclerosis. The process and secretion of proinflammatory cytokine IL-1β are controlled by the inflammasome. Here we showed the correlation of the innate immune system and afatinib, a tyrosine kinase inhibitor targeting epidermal growth factor receptor (EGFR) in non-small cell lung cancer. Methods: Murine Bone marrow derived macrophages (BMDMs), peritoneal macrophages (PMs) and THP-1 were used to check the effect of afatinib on the activation of NLRP3 inflammasome. The assembly of NLRP3 inflammasome was check by co-immunoprecipitation of NLRP3 and apoptosis-associated speck-like protein containing CARD (ASC), disuccinimidyl suberate (DSS)-cross link of ASC. Lipopolysaccharide (LPS)-induced sepsis and Alum-induced peritonitis were conducted to confirm that afatinib could inhibit the activation of NLRP3 in vivo. Peripheral blood mononuclear cells (PBMCs) from non-small cell lung cancer (NSCLC) patients before or after taking afatinib were used to check that afatinib inhibits inflammation in NSCLC therapy. Results: Our data showed that afatinib could inhibit the secretion of IL-1β in a dose-dependent manner in macrophage. Moreover, afatinib could inhibit the maturation of IL-1β and caspase-1 without affecting the precursors of IL-1β and caspase-1. Next, we found that afatinib could block the assembly of NLRP3 inflammasome and the ASC speck by blocking the interaction of the sensor protein NLRP3 and the adaptor protein ASC. We also found that afatinib was able to alleviate the LPS-induced sepsis in vivo. Conclusion: Our study found that afatinib could inhibit the activation of NLRP3 inflammasome in macrophage, providing new evidence that afatinib could target the innate immune system to control chronic inflammation. These investigations will provide significant experimental evidence in afatinib as therapeutic drug for non-small cell lung cancer or other tumors and NLRP3-related diseases and will explore new targets for afatinib.

Keywords: inflammasome, afatinib, inflammation, tyrosine kinase inhibitor

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Authors: Messis A., Adjebli A., Ayeche R., Talbi M., Tighilet K., Louardiane M.

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Cancers are the second cause of death worldwide. Prevalence and incidence of cancers is getting increased by aging and population growth. This study aims to predict and modeling the evolution of breast, Colorectal, Lung, Bladder and Prostate cancers over the period of 2014-2019. In this study, data were analyzed using time series analysis with double exponential smoothing method to forecast the future pattern. To describe and fit the appropriate models, Minitab statistical software version 17 was used. Between 2014 and 2019, the overall trend in the raw number of new cancer cases registered has been increasing over time; the change in observations over time has been increasing. Our forecast model is validated since we have good prediction for the period 2020 and data not available for 2021 and 2022. Time series analysis showed that the double exponential smoothing is an efficient tool to model the future data on the raw number of new cancer cases.

Keywords: cancer, time series, prediction, double exponential smoothing

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Authors: Ravid Inbar

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CaMKII (calcium-calmodulin dependent protein kinase II) makes up 2% of the protein in our brain and has a critical role in memory formation and long-term potentiation of neurons. Despite this, research has yet to uncover the role of one of the domains on the activation of this kinase. The following proposes to express the protein without the hub domain in E. coli, leaving only the kinase and regulatory segment of the protein. Next, a series of kinase assays will be conducted to elucidate the role the hub domain plays on CaMKII sensitivity to calcium/calmodulin activation. The hub domain may be important for activation; however, it may also be a variety of domains working together to influence protein activation and not the hub alone. Characterization of a protein is critical to the future understanding of the protein's function, as well as for producing pharmacological targets in cases of patients with diseases.

Keywords: CaMKII, hub domain, kinase assays, kinase + reg seg

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Authors: Junhong Li, Danni Cheng, Yaxin Luo, Xiaowei Yi, Ke Qiu, Wendu Pang, Minzi Mao, Yufang Rao, Yao Song, Jianjun Ren, Yu Zhao

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Background: The number of multiple cancer patients was increasing, and the impact of prior cancer history on salivary gland cancer patients remains unclear. Methods: Clinical, demographic and pathological information on salivary gland cancer patients were retrospectively collected from the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2017, and the characteristics and prognosis between patients with a prior cancer and those without prior caner were compared. Univariate and multivariate cox proportional regression models were used for the analysis of prognosis. A risk score model was established to exam the impact of treatment on patients with a prior cancer in different risk groups. Results: A total of 9098 salivary gland cancer patients were identified, and 1635 of them had a prior cancer history. Salivary gland cancer patients with prior cancer had worse survival compared with those without a prior cancer (p<0.001). Patients with a different type of first cancer had a distinct prognosis (p<0.001), and longer latent time was associated with better survival (p=0.006) in the univariate model, although both became nonsignificant in the multivariate model. Salivary gland cancer patients with a prior cancer were divided into low-risk (n= 321), intermediate-risk (n=223), and high-risk (n=62) groups and the results showed that patients at high risk could benefit from surgery, radiation therapy, and chemotherapy, and those at intermediate risk could benefit from surgery. Conclusion: Prior cancer history had an adverse impact on the survival of salivary gland cancer patients, and individualized treatment should be seriously considered for them.

Keywords: prior cancer history, prognosis, salivary gland cancer, SEER

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Authors: Salina Yahya Saddick

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Ovarian cancer remains the most lethal gynecological malignancy due to the lack of highly sensitive and specific screening tools for detection of early-stage disease. The OSE provides the progenitor cells for 90% of human ovarian cancers. Recent morphologic, immunohistochemical and molecular genetic studies have led to the development of a new paradigm for the pathogenesis and origin of epithelial ovarian cancer (EOC) based on a ualistic model of carcinogenesis that divides EOC into two broad categories designated Types I and II which are characterized by specific mutations, including KRAS, BRAF, ERBB2, CTNNB1, PTEN PIK3CA, ARID1A, and PPPR1A, which target specific cell signaling pathways. Type 1 tumors rarely harbor TP53. type I tumors are relatively genetically stable and typically display a variety of somatic sequence mutations that include KRAS, BRAF, PTEN, PIK3CA CTNNB1 (the gene encoding beta catenin), ARID1A and PPP2R1A but very rarely TP53 . The cancer stem cell (CSC) hypothesis postulates that the tumorigenic potential of CSCs is confined to a very small subset of tumor cells and is defined by their ability to self-renew and differentiate leading to the formation of a tumor mass. Potential protein biomarker miRNA, are promising biomarkers as they are remarkably stable to allow isolation and analysis from tissues and from blood in which they can be found as free circulating nucleic acids and in mononuclear cells. Recently, genomic anaylsis have identified biomarkers and potential therapeutic targets for ovarian cancer namely, FGF18 which plays an active role in controlling migration, invasion, and tumorigenicity of ovarian cancer cells through NF-κB activation, which increased the production of oncogenic cytokines and chemokines. This review summarizes update information on epithelial ovarian cancers and point out to the most recent ongoing research.

Keywords: epithelial ovarian cancers, somatic sequence mutations, cancer stem cell (CSC), potential protein, biomarker, genomic analysis, FGF18 biomarker

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Authors: Rekaya A. Shabbir, Marco Mingarelli, Glenn Flux, Ananya Choudhury, Tim A. D. Smith

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Introduction: Heterogeneity of dose distributions across a tumour is problematic for targeted radiotherapy. Gold nanoparticles (AuNPs) enhance dose-distributions of targeted radionuclides. The aim of this study is to demonstrate if tumour dose-distribution of targeted AuNPs radiolabelled with either of two radioisotopes (¹⁷⁷Lu and ⁹⁰Y) in breast cancer cells produced homogeneous dose distributions. Moreover, in vitro and in vivo studies were conducted to study the importance of receptor level on cytotoxicity of EGFR-targeted AuNPs in breast and colorectal cancer cells. Methods: AuNPs were functionalised with DOTA and OPPS-PEG-SVA to optimise labelling with radionuclide tracers and targeting with Erbitux. Radionuclides were chelated with DOTA, and the uptake of the radiolabelled AuNPs and targeted activity in vitro in both cell lines measured using liquid scintillation counting. Cells with medium (HCT8) and high (MDA-MB-468) EGFR expression were incubated with targeted ¹⁷⁷Lu-AuNPs for 4h, then washed and allowed to form colonies. Nude mice bearing tumours were used to study the biodistribution by injecting ¹⁷⁷Lu-AuNPs or ⁹⁰Y-AuNPs via the tail vein. Heterogeneity of dose-distribution in tumours was determined using autoradiography. Results: Colony formation (% control) was 81 ± 4.7% (HCT8) and 32 ± 9% (MDA-MB-468). High uptake was observed in the liver and spleen, indicating hepatobiliary excretion. Imaging showed heterogeneity in dose-distributions for both radionuclides across the tumours. Conclusion: The cytotoxic effect of EGFR-targeted AuNPs is greater in cells with higher EGFR expression. Dose-distributions for individual radiolabelled nanoparticles were heterogeneous across tumours. Further strategies are required to improve the uniformity of dose distribution prior to clinical trials.

Keywords: cancer cells, dose distributions, radionuclide therapy, targeted gold nanoparticles

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Authors: Olfat Shaker, Miriam Wadie, Reham Ali, Ayman Yosry

Abstract:

Colorectal cancer (CRC) is a major cause of mortality and morbidity and accounts for over 9% of cancer incidence worldwide. Silent information regulator 2 homolog 1 (SIRT1) gene is located in the nucleus and exert its effects via modulation of histone and non-histone targets. They function in the cell via histone deacetylase (HDAC) and/or adenosine diphosphate ribosyl transferase (ADPRT) enzymatic activity. The aim of this work was to study the relationship between SIRT1 polymorphism and its protein level in colorectal cancer patients in comparison to control cases. This study includes 2 groups: thirty healthy subjects (control group) & one hundred CRC patients. All subjects were subjected to: SIRT-1 serum level was measured by ELISA and gene polymorphisms of rs12778366, rs375891 and rs3740051 were detected by real time PCR. For CRC patients clinical data were collected (size, site of tumor as well as its grading, obesity) CRC patients showed high significant increase in the mean level of serum SIRT-1 compared to control group (P<0.001). Mean serum level of SIRT-1 showed high significant increase in patients with tumor size ≥5 compared to the size < 5 cm (P<0.05). In CRC patients, percentage of T allele of rs12778366 was significantly lower than controls, CC genotype and C allele C of rs 375891 were significantly higher than control group. In CRC patients, the CC genotype of rs12778366, was 75% in rectosigmoid and 25% in cecum & ascending colon. According to tumor size, the percentage of CC genotype was 87.5% in tumor size ≥5 cm. Conclusion: serum level of SIRT-1 and T allele, C allele of rs12778366 and rs 375891 respectively can be used as diagnostic markers for CRC patients.

Keywords: CRC, SIRT1, polymorphisms, ELISA

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Authors: Caroline Mendes, Mary McNamara, Orla Howe

Abstract:

Drug delivery systems are proposed for use in cancer treatment to specifically target cancer cells and deliver a therapeutic dose without affecting normal cells. For that purpose, the use of folate receptors (FR) can be considered a key strategy, since they are commonly over-expressed in cancer cells. In this study, cyclodextrins (CD) have being used as vehicles to target FR and deliver the chemotherapeutic drug, methotrexate (MTX). CDs have the ability to form inclusion complexes, in which molecules of suitable dimensions are included within their cavities. Here, β-CD has been modified using folic acid so as to specifically target the FR. Thus, this drug delivery system consists of β-CD, folic acid and MTX (CDEnFA:MTX). Cellular uptake of folic acid is mediated with high affinity by folate receptors while the cellular uptake of antifolates, such as MTX, is mediated with high affinity by the reduced folate carriers (RFCs). This study addresses the gene (mRNA) and protein expression levels of FRs and RFCs in the cancer cell lines CaCo-2, SKOV-3, HeLa, MCF-7, A549 and the normal cell line BEAS-2B, quantified by real-time polymerase chain reaction (real-time PCR) and flow cytometry, respectively. From that, four cell lines with different levels of FRs, were chosen for cytotoxicity assays of MTX and CDEnFA:MTX using the MTT assay. Real-time PCR and flow cytometry data demonstrated that all cell lines ubiquitously express moderate levels of RFC. These experiments have also shown that levels of FR protein in CaCo-2 cells are high, while levels in SKOV-3, HeLa and MCF-7 cells are moderate. A549 and BEAS-2B cells express low levels of FR protein. FRs are highly expressed in all the cancer cell lines analysed when compared to the normal cell line BEAS-2B. The cell lines CaCo-2, MCF-7, A549 and BEAS-2B were used in the cell viability assays. 48 hours treatment with the free drug and the complex resulted in IC50 values of 93.9 µM ± 15.2 and 56.0 µM ± 4.0 for CaCo-2 for free MTX and CDEnFA:MTX respectively, 118.2 µM ± 16.8 and 97.8 µM ± 12.3 for MCF-7, 36.4 µM ± 6.9 and 75.0 µM ± 10.5 for A549 and 132.6 µM ± 16.1 and 288.1 µM ± 26.3 for BEAS-2B. These results demonstrate that free MTX is more toxic towards cell lines expressing low levels of FR, such as the BEAS-2B. More importantly, these results demonstrate that the inclusion complex CDEnFA:MTX showed greater cytotoxicity than the free drug towards the high FR expressing CaCo-2 cells, indicating that it has potential to target this receptor, enhancing the specificity and the efficiency of the drug. The use of cell imaging by confocal microscopy has allowed visualisation of FR targeting in cancer cells, as well as the identification of the interlisation pathway of the drug. Hence, the cellular uptake and internalisation process of this drug delivery system is being addressed.

Keywords: cancer treatment, cyclodextrins, drug delivery, folate receptors, reduced folate carriers

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Authors: Fakhrosadat Sajjadian, Ramin Ghasemi Shayan

Abstract:

The tumor microenvironment plays an fundamental part in tumor start, movement, metastasis, and treatment resistance. It varies from ordinary tissue in terms of its extracellular network, vascular and lymphatic arrange, as well as physiological conditions. The clinical application of atomic cancer imaging is regularly prevented by the tall commercialization costs of focused on imaging operators as well as the constrained clinical applications and little showcase measure of a few operators. . Since numerous cancer types share comparable characteristics of the tumor microenvironment, the capacity to target these biomarkers has the potential to supply clinically translatable atomic imaging advances for numerous types encompassing cancer and broad clinical applications. Noteworthy advance has been made in focusing on the tumor microenvironment for atomic cancer imaging. In this survey, we summarize the standards and methodologies of later progresses in atomic imaging of the tumor microenvironment, utilizing distinctive imaging modalities for early discovery and conclusion of cancer. To conclude, The tumor microenvironment (TME) encompassing tumor cells could be a profoundly energetic and heterogeneous composition of safe cells, fibroblasts, forerunner cells, endothelial cells, flagging atoms and extracellular network (ECM) components.

Keywords: molecular, imaging, TME, medicine

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Authors: Paula Buldres, Jorge Toledo

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Objectives: This study aimed to characterize potential probiotic strains isolated from canine breast milk for use in dogs with enteropathies. Methodology: Six canine breast milk strains, one canine colostrum strain, and one control porcine breast milk strain were characterized. According to its functional properties of resistance to acids, different concentrations of bile salts, and pancreatin, its presumptive properties of safety and inhibitory effect on pathogens, non-cytotoxic characteristics, and adhesion to the intestine. The immunomodulatory effect of formulations with better probiotic characterization in vitro and in vivo was also analyzed. Results: Two strains characterized as potential probiotics were obtained, which corresponded to the canine strains (TUCO-16 and TUCO-17), presenting resistance to acidic pH, bile salts, and pancreatin, as well as an inhibitory effect on pathogenic Escherichia coli, Salmonella sp., and Clostridium perfringens. Strains TUCO-16 and TUCO-17 induced a significant increase in the expression of TNF-α and IL-8 in canine macrophages, respectively. Expression analyses of pattern recognition receptors in DH82 cells suggest that TUCO-16 and TUCO-17 might increase the TLR2 expression marker, and porcine strain (TUCO-4) increases the NOD2 expression marker. Based on the count obtained and the encapsulation yield, the best formulations correspond to FOS-Inulin for the TUCO-17 and TUCO-4 strains; Maltodextrin-Inulin for TUCO-16. All the strains are non-cytotoxic. The strain that showed the highest adhesion to intestinal epithelial cells was TUCO-17 with the FOS-Inulin formulation. On the other hand, the probiotics decreased the expression of pro-inflammatory markers in vivo, both in the intestine and in the spleen of mice. Conclusion: The combination of these three strains under study (TUCO-16, TUCO-17, and TUCO-4) would cover the probiotic properties in formulation and immunomodulation of all the markers under study.

Keywords: probiotics, gastrointestinal infec, dog, probiotic formulation, immunomodulatory probiotics

Procedia PDF Downloads 49

Authors: Ahmed Ali Torad

Abstract:

Background: Breast feeding maintains the maternal fetal immunological link, favours the transmission of immune-competence from the mother to her infant and is considered an important contributory factor to the neo natal immune defense system. Purpose: This study was conducted to investigate the effect of relaxation techniques on immunological properties of breast milk. Subjects and Methods: Thirty breast feeding mothers with a single, mature infant without any complications participated in the study. Subjects will be recruited from outpatient clinic of obstetric department of El Kasr El-Aini university hospital in Cairo. Mothers were randomly divided into two equal groups using coin toss method: Group (A) (relaxation training group) (experimental group): It will be composed of 15 women who received relaxation training program in addition to breast feeding and nutritional advices and Group (B) (control group): It will be composed of 15 women who received breast feeding and nutritional advices only. Results: The results showed that mean mother’s age was 28.4 ± 3.68 and 28.07 ± 4.09 for group A and B respectively, there were statistically significant differences between pre and post values regarding cortisol level, IgA level, leucocyte count and infant’s weight and height and there is only statistically significant differences between both groups regarding post values of all immunological variables (cortisol – IgA – leucocyte count). Conclusion: We could conclude that there is a statistically significant effect of relaxation techniques on immunological properties of breast milk.

Keywords: relaxation, breast, milk, immunology, lactation

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Authors: N. K. Caecar Pratiwi, Yunendah Nur Fuadah, Rita Magdalena, R. D. Atmaja, Sofia Saidah, Ocky Tiaramukti

Abstract:

Colon cancer or colorectal cancer is a type of cancer that attacks the last part of the human digestive system. Lymphoma and carcinoma are types of cancer that attack human’s colon. Colon cancer causes deaths about half a million people every year. In Indonesia, colon cancer is the third largest cancer case for women and second in men. Unhealthy lifestyles such as minimum consumption of fiber, rarely exercising and lack of awareness for early detection are factors that cause high cases of colon cancer. The aim of this project is to produce a system that can detect and classify images into type of colon cancer lymphoma, carcinoma, or normal. The designed system used 198 data colon cancer tissue pathology, consist of 66 images for Lymphoma cancer, 66 images for carcinoma cancer and 66 for normal / healthy colon condition. This system will classify colon cancer starting from image preprocessing, feature extraction using Principal Component Analysis (PCA) and classification using K-Nearest Neighbor (K-NN) method. Several stages in preprocessing are resize, convert RGB image to grayscale, edge detection and last, histogram equalization. Tests will be done by trying some K-NN input parameter setting. The result of this project is an image processing system that can detect and classify the type of colon cancer with high accuracy and low computation time.

Keywords: carcinoma, colorectal cancer, k-nearest neighbor, lymphoma, principle component analysis

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Authors: Cenza Rhoda, Falone Sunda, Elvis Kidzeru, Nonhlanhla P. Khumalo, Afolake Arowolo

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Introduction: The human FAM111B gene mutations are associated with POIKTMP, a rare multi-organ fibrosing disease. Recent studies also reported the overexpression of FAM111B in specific cancers. However, the role of FAM111B in these pathologies, particularly fibrosarcoma, remains unknown. Materials and Methods: FAM111B RNA expression in some cancer cell lines was assessed in silico and validated in vitro in these cell lines and skin fibroblasts derived from the South African family member affected by POIKTMP with the heterozygous FAM111B gene mutation: NM_198947.4: c.1861T>G (p. Tyr621Asp or Y621D) by qPCR and western blot. The cellular function of FAM111B was also studied in HT1080 using various cell-based functional assays and a simple and cost-effective PCR-RFLP method for genotyping/screening FAM111B gene mutations described. Results: Expression studies showed upregulated FAM111B mRNA and protein in the cancer cells. High FAM111B expression with robust nuclear localization occurred in HT1080. Additionally, expression data and cell-based assays indicated that FAM111B led to the upregulation of cell migration and decreased cell apoptosis and cell proliferation modulation. FAM111B Y621D mutation showed similar effects on cell migration but minimal impact on cell apoptosis. FAM111B mRNA and protein expression were markedly downregulated (p ≤ 0.05) in the patient's skin-derived fibroblasts. Lastly, the PCR-RFLP method successfully genotyped FAM111B Y621D gene mutation. Discussion: FAM111B is a cancer-associated nuclear protein: Its modulation by mutations may enhance cell migration and proliferation and decrease apoptosis, as seen in cancers and POIKTMP/fibrosis, thus representing a viable therapeutic target in these disorders. Furthermore, the PCR-RFLP method could prove a valuable tool for FAM111B mutation validation or screening in resource-constrained laboratories.

Keywords: FAM111B, POIKTMP, cancer, fibrosis, PCR-RFLP

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Authors: Yichao Liang, Biye Chen, Xiang Li, Steven R. Dimler

Abstract:

This study investigated the effects of adding calcium and magnesium chloride on heat and storage stability of milk protein concentrate-soy protein isolate (8:2 respectively) mixtures containing 10% w/w total protein subjected to the in-container sterilization (115 °C x 15 min). The particle size does not change when emulsions are heated at pH between 6.7 and 7.3 irrespective of the mixed protein ratio. Increasing concentration of divalent cation salts resulted in an increase in protein particle size, dry sediment formation and sediment height and a decrease in pH, heat stability and hydration in milk protein concentrate-soy protein isolate mixtures solutions on sterilization at 115°C. Fortification of divalent cation salts in milk protein concentrate-soy protein isolate mixture solutions resulted in an accelerated protein sedimentation and two unique sediment regions during accelerated storage stability testing. Moreover, the heat stability decreased upon sterilization at 115°C, with addition of MgCl₂ causing a greater increase in sedimentation velocity and compressibility than CaCl₂. Increasing pH value of protein milk concentrate-soy protein isolate mixtures solutions from 6.7 to 7.2 resulted in an increase in viscosity following the heat treatment. The study demonstrated that the type and concentration of divalent cation salts used strongly impact heat and storage stability of milk protein concentrate-soy protein isolate mixture nutritional beverages.

Keywords: divalent cation salts, heat stability, milk protein concentrate, soy protein isolate, storage stability

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Authors: Leila M. Carvalho, Maria Erica S. Oliveira, Arnoud C. Neto, Elza I. Ida, Massami Shimokomaki, Marta S. Madruga

Abstract:

The quality of broiler breast meat is changing as a result of the continuing emphasis on genetic selection for a more efficient meat production. Breast meat has been classified as PSE (pale, soft, exudative), DFD (dark, firm, dry) and normal color meat, and recently a third group has emerged: the so-called PFN (pale, firm, non-exudative) meat. This classification was based on pH, color and functional properties. The aim of this work was to confirm the existence of PFN and PSE meat by biochemical characterization and functional properties. Twenty four hours of refrigerated fillet, Pectoralis major, m. samples (n= 838) were taken from Cobb flocks 42-48 days old, obtained in Northeastern Brazil tropical region, the Northeastern, considered to have only dry and wet seasons. Color (L*), pH, water holding capacity (WHC), values were evaluated and compared with PSE group samples. These samples were classified as Normal (465.8), PSE meat (L*≥53; pH<5.8) and PFN (L*≥53; pH>5.8). The occurrence of control meat, PSE and PFN was 69.09%, 11.10% and 19.81%, respectively. Samples from PFN presented 4.0-5.0% higher WHC in relation to PSE meat and similar to control group. These results are explained by the fact that PSE meat syndrome occurs because of higher protein denaturation as the consequence of a simultaneous lower pH values under warm carcass sooner after slaughtering impairing the myofibril proteins functional properties. Conversely, PFN samples follow normal glycolysis rate maintaining the normal proteins activities. In conclusion, the results reported herein confirm the existence of this emerging broiler meat group with similar properties as control group and it should be considered as normal breast meat group.

Keywords: broiler breast meat, funcional properties, PFN, PSE

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Authors: Mehrnaz Aminifar

Abstract:

The relation between textural parameters and casein network on release of aromatic compounds was investigated over 90-days of ripening. Low DE maltodextrin and WPI were used to modify the textural properties of low fat brined cheese. Hardness, brittleness and compaction of casein network were affected by addition of maltodextrin and WPI. Textural properties and aroma release from cheese texture were affected by interaction of WPI protein-cheese protein and maltodexterin-cheese protein.

Keywords: aroma release, brined cheese, maltodexterin, WPI

Procedia PDF Downloads 334