Search results for: hereditary breast-ovarian cancer syndrome

Authors: Carlos Huertas, Reyes Juarez-Ramirez

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Public health is one of the most critical issues today; therefore, there is great interest to improve technologies in the area of diseases detection. With machine learning and feature selection, it has been possible to aid the diagnosis of several diseases such as cancer. In this work, we present an extension to the Heat Map Based Feature Selection algorithm, this modification allows automatic threshold parameter selection that helps to improve the generalization performance of high dimensional data such as mass spectrometry. We have performed a comparison analysis using multiple cancer datasets and compare against the well known Recursive Feature Elimination algorithm and our original proposal, the results show improved classification performance that is very competitive against current techniques.

Keywords: biomarker discovery, cancer, feature selection, mass spectrometry

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Authors: Zayd Parekh, Amish Prasad, Baraa Souman

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Postural orthostatic tachycardia syndrome (POTS) is characterized by orthostatic intolerance due to an exaggerated tachycardia in response to standing upright. This exaggerated orthostatic tachycardia is defined as the heart rate (HR) rising 30 beats above a baseline value while supine or seated within ten minutes. The tachycardia can lead to symptoms of orthostatic intolerance such as palpitations, lightheadedness, exercise intolerance, fatigue, and anxiety. POTS can go undiagnosed for many years due to its similarities with other cardiac and psychiatric conditions and nonspecific presentation, making it crucial to raise awareness for it in the medical field. The following case study discusses a 30-year-old female who was evaluated in the emergency room several times before being referred to the clinic for POTS. An overview of what tests are performed with this patient is also provided, highlighting the diagnostic work-up for POTS and the process of ruling out other differentials being considered. Finally, the epidemiology, the various theories regarding its pathophysiology, the diagnostic process, and pharmacological and non-pharmacological management for POTS are reviewed.

Keywords: orthostatic intolerance, postural orthostatic tachycardia syndrome, syncope, tachycardia

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Authors: Abigail Tan, Heng Liang Tan, Vanessa Ding, James Hui, Eng Hin Lee, Andre Choo

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Introduction: Comparative oncology investigates the similarities in spontaneous carcinogenesis between humans and animals, in order to identify treatments that can benefit these patients. Companion animals (CA), like canines and felines, are of special interest when it comes to studying human cancers due to their exposure to the same environmental factors and develop tumours with similar features. The purpose of this study is to explore the cross-reactivity of monoclonal antibodies (mAbs) across cancers in humans and CA. Material and Methods: A panel of CA mAbs generated in the lab was screened on multiple human cancer cell lines through flow cytometry to identify for positive binders. Shortlisted candidates were then characterised by biochemical and functional assays e.g., antibody-drug conjugate (ADC) and western blot assays, including glycan studies. Results: Candidate mAb KP52 was generated from whole-cell immunisation using feline mammary carcinoma. KP52 showed strong positive binding to human cancer cells, such as breast cancer and ovarian cancer. Furthermore, KP52 demonstrated strong killing ( > 50%) as an ADC with Saporin as the payload. Western blot results revealed the molecular weight of the antigen targets to be approximately 45kD and 50kD under reduced conditions. Glycan studies suggest that the epitope is glycan in nature, specifically an O-linked glycan. Conclusion: Candidate mAb KP52 has a therapeutic potential as an ADC against feline mammary cancer, human ovarian cancer, human mammary cancer, human pancreatic cancer, and human gastric cancer.

Keywords: ADC, comparative oncology, mAb, therapeutic

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Authors: Dina Fatmawati, Sofia Mubarika, Mae Sri Wahyuningsih

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Chemotherapy for breast cancer is largely ineffective, but innovative combinations of chemotherapeutic agents and natural compounds represent a promising strategy. In our previous study, the combination of Doxorubicin (Dox) and ethanolic extract of Dioscorea esculenta tuber ((EED) was found to have a synergistic effect on T47D human breast cancer cell line. In this study, we investigated the apoptotic effect of the combination on T47D human breast cancer cells and normal fibroblasts cell line and its effects on the expression of Caspase-3 and cleaved poly (ADP-Ribose) Polymerase-1 (cPARP-1) protein. T47D cell lines and fibroblasts cells were treated with the combination of Dox and EED. Apoptotic effect of the combination was determined using flow cytrometry assay. Protein expressions were determined by immunocytochemistry staining. The percentage of apoptotic cells were significantly higher in T47D cell lines (75%) than that of in fibroblast cells (23%). The expression of Caspase 3 (84.53%) and cPARP-1 (83.36%) were significantly higher in the cancer cell lines than those of normal cells. These results indicate that the combination of doxorubicin and Dioscorea esculenta is a promising candidate for the treatment of breast cancer cells.

Keywords: Dioscorea esculenta, Doxorubicin, apoptosis, immunocytochemistry, cancer cells

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Authors: Selim A., Albasher N., Bakrmom G., Alanzi S.

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Irritable bowel syndrome (IBS) is a chronic functional bowel disorder characterized by abdominal discomfort or pain and associated with alteration in frequency and/or form of bowel habit among other symptoms. This diagnosis is associated with increased levels of psychological distress, maladaptive coping, genetic risk factors, abnormal small and colonic intestine transit, change in stool frequency or form and abdominal discomfort or pain. Aim: The aim of the study was to assess psychological alarm among individuals suffering from Irritable Bowel Syndrome (IBS). Methods: A cross-sectional correlational research design was used to conduct the current study. A convenience sample of 504 participants was included in the present study. Data were collected using a self-report questionnaire. The questionnaire included socio-demographic data, ROME III to identify Irritable Bowel Syndrome (IBS) and Psychological Alarm Questionnaire. Results: Out of 504 participants who reported abdominal discomfort, 297 (58.9 %) participants met the diagnostic criteria of IBS. The mean age of the IBS participants was 30.16 years, females composed 75.1% of the IBS participants, and 55.2% did not seek medical help. Psychological alarms such as feeling anxious, feeling depressed, having suicidal ideations, bodily pain, having impaired functioning due to pain and feeling unable to cope with pain were significantly high among IBS individuals when compared to individuals not suffering from IBS. Psychological alarms such as feeling anxious, feeling depressed, having suicidal ideations, bodily pain, having impaired functioning due to pain and feeling unable to cope with pain were significantly high among IBS individuals compared to individuals not suffering from IBS. Conclusion: IBS is highly associated with significant psychological alarms including depression, anxiety and suicidal ideas.

Keywords: abdominal pain , irritable bowel syndrome, distress, psychological alarms

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Authors: Azar Heidarizadi, Mahdieh Salimi, Hossein Mozdarani

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Introduction: As a complex disease, breast cancer results from several genetic and epigenetic changes. Lactoferrin, a member of the transferrin family, is reported to have a number of biological functions, including DNA synthesis, immune responses, iron transport, etc., any of which could play a role in tumor progression. This study aimed to investigate the bioinformatics data and experimental assay to find the pattern of promoter methylation and gene expression of LTF in breast cancer to study its potential role in cancer management. Material and Methods: To evaluate the LTF promoter's methylation status, we studied the MS-PCR and Real-Time PCR on samples from patients with breast cancer and normal cases. This study includes 67 patient samples, including tumoral, plasma, and normal tissue adjacent samples, as well as 30 plasma samples from standard cases and 10 tissue samples of breast reduction cases. Subsequently, bioinformatics analyses such as cBioPortal databases, string, and geomatics were conducted to disclose the prognostic value of LTF in breast cancer progression. Results: The analysis of LTF expression showed an inverse relationship between the expression level of LTF and the stages of tissues of breast cancer patients (p<0.01). In fact, stages 1 and 2 had a high expression in LTF, while, in stages 3 and 4, a significant reduction was observable (p < 0.0001). LTF expression frequently alters with a decrease in the expression in ER+, PR+, and HER2+ patients (P < 0.01) and an increase in the expression in the TNBC, LN¯, ER¯, and PR- patients (P < 0.001). Also, LTF expression is significantly associated with metastasis and lymph node involvement factors (P < 0.0001). The sensitivity and specificity of LTF were detected, respectively. A negative correlation was detected between the results of level expression and methylation of the LTF promoter. Conclusions: The altered expression of LTF observed in breast cancer patients could be considered as a promotion in cell proliferation and metastasis even in the early stages of cancer.

Keywords: LTF, expression, methylation, breast cancer

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Authors: Srisopa Ruangnoo, Arunporn Itharat

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The ethanolic and aqueous extracts of Parkia javanica Merr. germinating seeds and Parkia speciosa Hassk. seeds were evaluated for cytotoxic activity against three different types of human cancer cell lines including colon cancer (LS174T), breast cancer (MCF-7) and prostate cancer (PC3) using sulforhodamine B (SRB) assay. The fresh plant parts were divided into 2 parts. The first part was extracted by maceration with 95% ethanol for 3 days and then filtered, and the filtrates were evaporated by rotary evaporator. The other part was squeezed and filtered. Then the filtrates were dried by freeze dryer. The screening found that the aqueous extract of P. javanica Merr. germinating seeds exhibited more than 70% inhibition (at concentration 50 µg/ml) against all types of human cancer cells. The aqueous extract of P. javanica Merr. germinating seeds showed the highest cytotoxic activity against MCF-7 with the IC50 value as 5.63 µg/ml. The aqueous extract of P. javanica Merr. germinating seeds also showed high cytotoxic activity against PC3 and LS174T with the IC50 values as 10.79 and 11.40 µg/ml, respectively. In conclusion, P. javanica Merr. germinating seed is a natural source of anticancer activity and further research to isolate active compounds from this plant should be undertaken.

Keywords: cytotoxic activity, Parkia javanica Merr., Parkia speciosa Hassk., human cancer cell lines

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Authors: Hui-Hsin Huang, Sheng-Tung Huang, Chi-Ming Lee, Chiao-Han Yen, Chun-Mao Lin

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At initiation stage, there are no symptoms at initiation stage; however, at late stage, patients suffer symptoms as soon as ovarian cancer metastasis. Moreover, ovarian cancer cells are resistant to some anti-ovarian cancer drugs in clinical. Thus, it is very important to find an effective treatment for resistant ovarian cancer. Anthraquinone derivatives are able to induce DNA damage and lead to cell apoptosis, so several derivatives have been used for clinical application. Therefore, to explore more effective anti-ovarian cancer drugs, this study investigates the mechanism of three new anthraquinone compounds bearing different functional groups to camptothecin-resistance ovarian cell line A2780R2000. Cell viability was determined by MTT assay after treating A2780R2000 with the three new anthraquinone compounds. The results indicated that IC50 values are 33.44μM (Compound I), 25.77μM (Compound II) and 24.59μM (Compound III). Next, through cell cycle analysis, the results demonstrated that three new anthraquinone compounds not only induced A2780R2000 cell cycle arrest at early stage but also apoptosis at late stage. Besides, through apoptosis assay, the results indicated new anthraquinone compound induced apoptosis at late stage. Furthermore, the results of western blot show that the three new anthraquinone compounds lead to A2780R2000 apoptosis through intrinsic pathway. Theses results suggested that three new anthraquinone compounds may be potential new drugs for clinical cancer treatment in the future.

Keywords: anthraquinone, camptothecin, resistance, ovarian cancer

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Authors: Aadil Khan, Yasser Chomayil, P. P. Venugopalan

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Background: Budd-Chiari syndrome is caused by thrombosis of the hepatic veins and/or the thrombosis of the intrahepatic or suprahepatic IVC. The etiology remains idiopathic in 16% -35% of cases. Malignancy, rheumatological disorder, myeloproliferative disease, inheritable coagulopathy, infection or hyperestrogen state can be identified in many cases. Methodology: Review of case records of the patient presented to Aster Medcity, Emergency Department, Cochin. Introduction:17 years old female was presented to ED with fever, jaundice and abdominal distention since 1 week. O/E: Pallor+, icterus+. Abdomen- gross distension+, shifting dullness+, generalized anasarca+. USG abdomen showed hepatomegaly with mild coarse echotexture and moderate to gross ascites. CT abdomen and chest showed hepatomegaly with thrombosis of all three hepatic vein and moderate ascites suggestive of Budd-Chiari syndrome. Patient was taken for catheter vein thrombolysis. Venogram done the next day revealed almost > 50% opening of the right hepatic vein. Concurrent doppler showed colour and doppler signals in middle hepatic veins. She gradually improved and was discharged home on anticoagulant and adviced regular follow up. Conclusion: Being a rare disease in this young population, high suspicion is required when evaluating young patients with abdominal pain and jaundice.

Keywords: Budd-Chiari syndrome, rare disease, abdominal pain, India

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Authors: Lubomir Vecera, Tomas Gabrhelik, Benjamin Tolmaci, Josef Srovnal, Emil Berta, Petr Prasil, Petr Stourac

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Cancer is the second leading cause of death worldwide and colon cancer is the second most common type of cancer. Currently, there are only a few studies evaluating the effect of postoperative analgesia on the prognosis of patients undergoing radical colon cancer surgery. Postoperative analgesia in patients undergoing colon cancer surgery is usually managed in two ways, either with strong opioids (morphine, piritramide) or epidural analgesia. In our prospective study, we evaluated the effect of postoperative analgesia on the presence of circulating tumor cells or minimal residual disease after colon cancer surgery. A total of 60 patients who underwent radical colon cancer surgery were enrolled in this prospective, randomized, two-center study. Patients were randomized into three groups, namely piritramide, morphine and postoperative epidural analgesia. We evaluated the presence of carcinoembryonic antigen (CEA) and cytokeratin 20 (CK-20) mRNA positive circulating tumor cells in peripheral blood before surgery, immediately after surgery, on postoperative day two and one month after surgery. The presence of circulating tumor cells was assessed by quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR). In the priritramide postoperative analgesia group, the presence of CEA mRNA positive cells was significantly lower on a postoperative day two compared to the other groups (p=0.04). The value of CK-20 mRNA positive cells was the same in all groups on all days. In all groups, both types of circulating tumor cells returned to normal levels one month after surgery. Demographic and baseline clinical characteristics were similar in all groups. Compared with morphine and epidural analgesia, piritramide significantly reduces the amount of CEA mRNA positive circulating tumor cells after radical colon cancer surgery.

Keywords: cancer progression, colon cancer, minimal residual disease, perioperative analgesia.

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Authors: Wenxing Chen, Guangying Chen, Yin Lu, Shile Huang

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Cryptotanshinone (CPT), a fat-soluble tanshinone from Salvia miltiorrhiza Bunge, has been demonstrated to inhibit mTOR pathway, resulting in inhibition of cancer cell proliferation. However, the molecular mechanism how CPT acts on mTOR is unknown. Here, cancer cells expressing rapamycin-resistant mutant mTOR are also sensitive to CPT, while phosphorylation of AMPK and TSC2 was activated, suggesting that CPT inhibition of mTOR maybe due to activating upstream of mTOR, AMPK, but not directly binding to and inhibiting mTOR. Further results indicated that Compound C, inhibitor of AMPK, could partially reversed CPT inhibition effect on cancer cells, and dominant-negative AMPK in cancer cells conferred resistance to CPT inhibition of 4EBP1 and phosphorylation of S6K1, as well as sh-AMPK. Furthermore, compared with MEF cells with AMPK positive, MEF cells with AMPK knock out are less sensitive to CPT by the findings that 4E-BP1 and phosphorylation of S6K1 express comparatively much. Furthermore, downexpression of TSC2 slightly recovered expression of 4EBP1 and phosphorylation of S6K1, while co-immunoprecipitation of TSC2 did not affect expression of TSC1 by CPT. Collectively, the above-mentioned results suggest that CPT inhibited mTOR pathway mostly was due to activation of AMPK-TSC2 pathway rather than specific inhibition of mTOR and then induction of subsequent lethal cellular effect.

Keywords: cryptotanshinone, AMPK, TSC2, mTOR, cancer cells

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Authors: Emad A. Shalaby

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Cancer is a disease that causes abnormal cell proliferation and invades nearby tissues. Lung cancer is the second most frequent cancer worldwide. Natural anti-cancer drugs have been developed with low side effects and toxicity. Citrus peels and extracts have been demonstrated to have significant pharmacological and physiological effects as a result of the high concentration of phenolic compounds found in citrus fruits, particularly peels. Tangerine peels can serve as an effective source of bioactive substances such as phenolics, flavonoids, and catechins, which have antioxidant, antibacterial, anticancer, and anti-inflammatory properties. Consequently, this work aims to determine the anticancer activity of ethanol extract of Tangerine peels against the A549 cell line and identify the phenolic compound profile (19 compounds) by using HPLC. Anticancer and antioxidant potentials of the extract were evaluated by MTT assay and TLC- TLC-bioautography sprayed with DPPH reagent, respectively. The obtained results revealed that tangerine peel extract showed significant activity against the A549 cell line with IC50 of 97.66 μg/mL. HPLC analysis proved that the highest concentration is naringenin 464.05 mg/g. More studies indicate that naringenin has significant anticancer potential on A549 cancer cells. The results showed that naringenin binds t0 EGFR protein in A549 with high binding affinity and thus may reduce lung cancer cell migration and enhance the apoptosis of cancer cells. From the obtained results it could be concluded that tangerine peel extract is an effective anti-cancer agent that may potentially serve as a natural therapeutic option for lung cancer treatment.

Keywords: tangerine peel, A549 cell line, anticancer, naringenin, HPLC analysis, naringenin, TLC bioautography

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Authors: Cecília M. Antão, Paulo Jorge Nogueira

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Breast cancer (BC) is the first cause of cancer mortality among Portuguese women. This retrospective observational study aimed at identifying comorbidities associated with BC female patients admitted to Portuguese public hospitals (2010-2018), investigating the effect of comorbidities on BC mortality rate, and building a predictive model using logistic regression. Results showed that the BC mortality in Portugal decreased in this period and reached 4.37% in 2018. Adjusted odds ratio indicated that secondary malignant neoplasms of liver, of bone and bone marrow, congestive heart failure, and diabetes were associated with an increased chance of dying from breast cancer. Although the Lisbon district (the most populated area) accounted for the largest percentage of BC patients, the logistic regression model showed that, besides patient’s age, being resident in Bragança, Castelo Branco, or Porto districts was directly associated with an increase of the mortality rate.

Keywords: breast cancer, comorbidities, logistic regression, adjusted odds ratio

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Authors: Amer A. Hasan, Mehri Igci, Ersin Borazan, Rozhgar A. Khailany, Emine Bayraktar, Ahmet Arslan

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Gastric cancer (GC) has high morbidity and fatality rate in various countries and is still one of the most frequent and deadly diseases. Novel mitogenic and motogenic Gastrokine1 (GKN1) and Gastrokine 2 (GKN2) genes that are highly expressed in the normal stomach epithelium and plays an important role in maintaining the integrity and homeostasis of stomach mucosal epithelial cells. Significant loss of copy number and mRNA transcript of GKN1 and GKN2 gene expression were frequently observed in all types of gastric cancer. In this study, 47 paired samples that were grouped according to the types of gastric cancer and the clinical characteristics of the patients, including gender and average of age were investigated with gene expression analysis and mutation screening by monetering RT-PCR, SSCP and nucleotide sequencing techniques. Both GKN1 and GKN2 genes were observed significantly reduced found by (Wilcoxon signed rank test; p<0.05). As a result of gene screening, no mutation (no different genotype) was detected. It is considered that gene mutations are not the cause of inactivation of gastrokines. In conclusion, the mRNA expression level of GKN1 and GKN2 genes statistically was decreased regardless the gender, age or cancer type of patients. Reduced of gastrokine genes seems to occur at the initial steps of cancer development. In order to understand the investigation between gastric cancer and diagnostic biomarker; further analysis is necessary.

Keywords: gastric cancer, diagnostic biomarker, nucleotide sequencing, semi-quantitative RT-PCR

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Authors: Mohammed Moustafa, Khaled Ayad, Waleed Reda

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Shoulder impingement syndrome is the most common disorder of the shoulder, resulting in functional loss and disability. Objective: This study was designed to compare between the effects of scapular muscle training versus rhythmic stabilization exercises in treatment of shoulder impingement syndrome. Methods: Thirty patients participated in this study; they were assigned randomly into two experimental groups. The first experimental group (A) consisted of 15 patients with a mean age (21.87±2.72) years; they received graduated rhythmic stabilization exercises and stretching of the posterior capsule. The second experimental group (B) consisted of 15 patients with a mean age (22.27±2.94) years; they received scapular muscle training exercises in addition to stretching of the posterior capsule. Treatment was given three times per week, every other day, for four consecutive weeks. Patients have been evaluated pretreatment and post treatment for shoulder pain severity and functional disability. Results: Both groups showed highly statistical significant reduction in pain severity and functional disability measured post-treatment when compared with their corresponding values in pretreatment assessment. Conclusion: Both of rhythmic stabilization exercises and scapular muscle training are effective interventions to reduce shoulder pain severity and functional disability.

Keywords: impingement syndrome, scapular exercises, rhythmic stabilization exercises, posterior capsule stretch

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Authors: Gökçe Erdemir, İlhan Yaylım, Serap Erdem-Kuruca, Musa Mutlu Can

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It has been determined that the main reason for the death of cancer disease is caused by metastases rather than the primary tumor. The cells that leave the primary tumor and enter the circulation and cause metastasis in the secondary organs are called "circulating tumor cells" (CTCs). The presence and number of circulating tumor cells has been associated with poor prognosis in many major types of cancer, including breast, prostate, and colorectal cancer. It is thought that knowledge of circulating tumor cells, which are seen as the main cause of cancer-related deaths due to metastasis, plays a key role in the diagnosis and treatment of cancer. The fact that tissue biopsies used in cancer diagnosis and follow-up are an invasive method and are insufficient in understanding the risk of metastasis and the progression of the disease have led to new searches. Liquid biopsy tests performed with a small amount of blood sample taken from the patient for the detection of CTCs are easy and reliable, as well as allowing more than one sample to be taken over time to follow the prognosis. However, since these cells are found in very small amounts in the blood, it is very difficult to capture them and specially designed analytical techniques and devices are required. Methods based on the biological and physical properties of the cells are used to capture these cells in the blood. Early diagnosis is very important in following the prognosis of tumors of epithelial origin such as breast, lung, colon and prostate. Molecules such as EpCAM, vimentin, and cytokeratins are expressed on the surface of cells that pass into the circulation from very few primary tumors and reach secondary organs from the circulation, and are used in the diagnosis of cancer in the early stage. For example, increased EpCAM expression in breast and prostate cancer has been associated with prognosis. These molecules can be determined in some blood or body fluids to be taken from patients. However, more sensitive methods are required to be able to determine when they are at a low level according to the course of the disease. The aim is to detect these molecules found in very few cancer cells with the help of sensitive, fast-sensing biosensors, first in breast cancer cells reproduced in vitro and then in blood samples taken from breast cancer patients. In this way, cancer cells can be diagnosed early and easily and effectively treated.

Keywords: electrochemical biosensors, breast cancer, circulating tumor cells, EpCAM, Vimentin, Cytokeratins

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Authors: Nino Gogatishvili, Davit Kvernadze, Giorgi Japharidze

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Background and aims: Landau Kleffner syndrome (LKS) is a rare disorder with epileptic seizures and acquired aphasia. It usually starts in initially healthy children. The first symptoms are language regression and behavioral disturbances, and the sleep EEG reveals abnormal epileptiform activity. The aim was to discuss the efficacy of Clobazam for Landau Kleffner syndrome. Case report: We report a case of an 11-year-old boy with an uneventful pregnancy and delivery. He began to walk at 11 months and speak with simple phrases at the age of 2,5 years. At the age of 18 months, he had febrile convulsions; at the age of 5 years, the parents noticed language regression, stuttering, and serious behavioral dysfunction, including hyperactivity, temper outbursts. The epileptic seizure was not noticed. MRI was without any abnormality. Neuropsychological testing revealed verbal auditory agnosia. Sleep EEG showed abundant left fronto-temporal spikes, reaching over 85% during non-rapid eye movement sleep (non-REM sleep). Treatment was started with Clobazam. After ten weeks, EEG was improved. Stuttering and behavior also improved. Results: Since the start of Clobazam treatment, stuttering and behavior improved. Now, he is 11 years old, without antiseizure medication. Sleep EEG shows fronto-temporal spikes on the left side, over 10-49 % of non-REM sleep, bioccipital spikes, and slow-wave discharges and spike-waves. Conclusions: This case provides further support for the efficacy of Clobazam in patients with LKS.

Keywords: Landau-Kleffner syndrome, antiseizure medication, stuttering, aphasia

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Authors: Dipali Dhawan

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Cancerous epithelial cells are confined to a primary site by the continued expression of adhesion molecules and the intact basal lamina. However, as the cancer progresses some cells are believed to undergo an epithelial-mesenchymal transition (EMT) event, leading to increased motility, invasion and, ultimately, metastasis of the cells from the primary tumour to secondary sites within the body. These disseminated cancer cells need the ability to self-renew, as stem cells do, in order to establish and maintain a heterogeneous metastatic tumour mass. Identification of the specific subpopulation of cancer stem cells amenable to the process of metastasis is highly desirable. In this study, we have isolated and characterized cancer stem cells from luminal and basal breast cancer cell lines (MDA-MB-231, MDA-MB-453, MDA-MB-468, MCF7 and T47D) on the basis of cell surface markers CD44 and CD24; as well as Side Populations (SP) using Hoechst 33342 dye efflux. The isolated populations were analysed for epithelial and mesenchymal markers like E-cadherin, N-cadherin, Sfrp1 and Vimentin by Western blotting and Immunocytochemistry. MDA-MB-231 cell lines contain a major population of CD44+CD24- cells whereas MCF7, T47D and MDA-MB-231 cell lines show a side population. We observed higher expression of N-cadherin in MCF-7 SP cells as compared to MCF-7NSP (Non-side population) cells suggesting that the SP cells are mesenchymal like cells and hence express increased N-cadherin with stem cell-like properties. There was an expression of Sfrp1 in the MCF7- NSP cells as compared to no expression in MCF7-SP cells, which suggests that the Wnt pathway is expressed in the MCF7-SP cells. The mesenchymal marker Vimentin was expressed only in MDA-MB-231 cells. Hence, understanding the breast cancer heterogeneity would enable a better understanding of the disease progression and therapeutic targeting.

Keywords: cancer stem cells, epithelial to mesenchymal transition, biomarkers, breast cancer

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Authors: Atif Zafar Khan, Swarnendra Singh, Imrana Naseem

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Breast cancer is one of the most frequent malignancies in women worldwide and a leading cause of cancer-related deaths among women. Therefore, there is a need to identify new chemotherapeutic strategies for cancer treatment. Unlike normal cells, cancer cells contain elevated copper levels which play an integral role in angiogenesis. Copper is an important metal ion associated with the chromatin DNA, particularly with guanine. Thus, targeting copper via copper-specific chelators in cancer cells can serve as effective anticancer strategy. Keeping in view these facts, we evaluated the anticancer activity and copper-dependent cytotoxic effect of coumestrol (phytoestrogen in soybean products) in breast cancer MCF-7 cells. Coumestrol inhibited proliferation and induced apoptosis in MCF-7 cells, which was prevented by copper chelator neocuproine and ROS scavengers. Coumestrol treatment induced ROS generation coupled to DNA fragmentation, up-regulation of p53/p21, cell cycle arrest at G1/S phase, mitochondrial membrane depolarization and caspases 9/3 activation. All these effects were suppressed by ROS scavengers and neocuproine. These results suggest that coumestrol targets elevated copper for redox cycling to generate ROS leading to DNA fragmentation. DNA damage leads to p53 up-regulation which directs the cell cycle arrest at G1/S phase and promotes caspase-dependent apoptosis of MCF-7 cells. In conclusion, coumestrol induces pro-oxidant cell death by chelating cellular copper to produce copper-coumestrol complexes that engages in redox cycling in breast cancer cells. Thus, targeting elevated copper levels might be a potential therapeutic strategy for selective cytotoxic action against malignant cells.

Keywords: apoptosis, breast cancer, copper chelation, coumestrol, reactive oxygens species, redox cycling

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Authors: Siddhant Rao

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Studies estimate that there will be 266,120 new cases of invasive breast cancer and 40,920 breast cancer induced deaths in the year of 2018 alone. Despite the pervasiveness of this affliction, the current process to obtain an accurate breast cancer prognosis is tedious and time consuming. It usually requires a trained pathologist to manually examine histopathological images and identify the features that characterize various cancer severity levels. We propose MITOS-RCNN: a region based convolutional neural network (RCNN) geared for small object detection to accurately grade one of the three factors that characterize tumor belligerence described by the Nottingham Grading System: mitotic count. Other computational approaches to mitotic figure counting and detection do not demonstrate ample recall or precision to be clinically viable. Our models outperformed all previous participants in the ICPR 2012 challenge, the AMIDA 2013 challenge and the MITOS-ATYPIA-14 challenge along with recently published works. Our model achieved an F- measure score of 0.955, a 6.11% improvement in accuracy from the most accurate of the previously proposed models.

Keywords: breast cancer, mitotic count, machine learning, convolutional neural networks

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Authors: Rahul Shrivastava, Manish Tripathi, Mohmmad Yasir, Shailesh Singh

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Life style changes and depletion in atmospheric ozone layer in recent decades lead to increase in skin cancer including both melanoma and nonmelanomas. Natural products which were obtained from different plant species have the potential of anti skin cancer activity. In regard of this, present study focuses the potential effect of Glycosmis pentaphylla against anti skin cancer activity. Different Phytochemical constituents which were present in the roots of Glycosmis pentaphylla were identified and were used as ligands after sketching of their structures with the help of ACD/Chemsketch. These ligands are screened for their anticancer potential with proteins which are involved in skin cancer effects with the help of pyrx software. After performing docking studies, results reveal that Noracronycine secondary metabolite of Glycosmis pentaphylla shows strong affinity of their binding energy with Ribosomal S6 Kinase 2 (2QR8) protein. Ribosomal S6 Kinase 2 (2QR8) has an important role in the cell proliferation and transformation mediated through by N-terminal kinase domain and was induced by the tumour promoters such as epidermal growth factor. It also plays a key role in the neoplastic transformation of human skin cells and in skin cancer growth. Noracronycine interact with THR-493 and MET-496 residue of Ribosomal S6 Kinase 2 protein with binding energy ΔG = -8.68 kcal/mole. Thus on the basis of this study we can say that Noracronycine which present in roots of Glycosmis pentaphylla can be used as lead compound against skin cancer.

Keywords: glycosmis pentaphylla, pyrx, ribosomal s6 kinase, skin cancer

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Authors: Augustine Ndudi Egere, Shehu Adamu, Esther Ishaya Solomon

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As internet accessibility and smartphones continue to increase in Nigeria, Africa’s most populous country, social media platforms have become ubiquitous, causing students of 18-25 age brackets to spend more time on social media. The research investigated the impact of prolonged social media use on the physical health of students, with a specific focus on computer vision syndrome, hand pain, headaches and mental status. The study adopted a mixed-methods approach combining quantitative surveys to gather statistical data on usage patterns and symptoms, along with qualitative interviews into the experiences and perceptions of medical practitioners concerning cases under study within the geopolitical region. The result was analyzed using Regression analysis. It was observed that there is a significant correlation between social media usage by the students in the study age bracket concerning computer vision syndrome, hand pain, headache and general mental status. The research concluded by providing valuable insights into potential interventions and strategies to mitigate the adverse effects of excessive social media use on student well-being and recommends, among others, that educational institutions, parents, and students themselves collaborate to implement strategies aimed at promoting responsible and balanced use of social media.

Keywords: social media, student health, computer vision syndrome, hand pain, headaches, mental staus

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Authors: Srie Rezeki Nur Endah, Richa Mardianingrum

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Cancer is one of the most feared diseases and is considered the leading cause of death worldwide. Generally, cancer drugs are synthetic drugs with relatively more expensive prices and have harmful side effects, so many people turn to traditional medicine, for example by utilizing herbal medicine. Erythrina poeppigiana is one of the plants that can be used as a medicinal plant containing 10,11-dihidroerisodin compounds that are useful anticancer etnofarmakologi. The purpose of this study was to identify the target of 10,11 dihydroerisodin receptor compound as in silico anticancer candidate. The pure isolate was tested physicochemically by MS (Mass Spectrometry), UV-Vis (Ultraviolet – Visible), IR (Infra Red), 13C-NMR (Carbon-13 Nuclear Magnetic Resonance), 1H-NMR (Hydrogen-1 Nuclear Magnetic Resonance), to obtain the structure of 10,11-dihydroerisodin alkaloid compound then identified to target receptors in silico. From the results of the study, it was found that 10,11-dihydroerisodin compound can work on the Serine / threonine-protein kinase Chk1 receptor that serves as an anti-cancer candidate.

Keywords: anti-cancer, Erythrina poeppigiana, target receptor, 10, 11- dihidroerisodin

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Authors: Rawan Al-Nemari, Abdulrahman Al-Senaidy, Abdelhabib Semlali

Abstract:

Background and objectives: The most common cause of death in women worldwide is breast cancer. Regarding all chemotherapy disadvantages and side effects, it’s becoming necessary to identify natural products that target cancer cells with lesser harmful side effects on non-targeted cells and biological environment. Different parts of A. squamosa L., commonly known as custard apple, show varied therapeutic effects. The objective of this study is to investigate in vitro and in vivo, the anti-cancer activity of A. squamosa leaves extract. Methods: The physiological responses using MTT, nucleus staining, and LDH assays were used to evaluate cell survival and proliferation in both ER+ and ER- cells when they were exposed to extract. Monolayer wound repair assay was used to investigate the effect of extracts on cell migration. Apoptotic gene’s expression was investigated by real-time polymerase chain reaction. To study the effect of the extract on the size of tumor, breast cancer induced rats were used. Results: A. squamosa leaves extract showed high anti-proliferative and cytotoxicity effects against different breast cancer cell lines with high concentration, 100 ug/ml. The extracts have reduced the cells wound closure. Polymerase chain reaction revealed downregulation of Bcl-2 and upregulation of Bax. In breast cancer model animal developed in our laboratory, after 4 weeks treatment, treated groups have shown smaller tumor size in comparison with control group (n=4). Conclusion: These results suggest that A. squamosa leaves extract has anti-cancer activity against breast cancer in both in vitro and in vivo, and it may be developed as a potential novel agent to treat breast cancer.

Keywords: apoptosis, breast cancer, migration, proliferation

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Authors: Rozhgar A. Khailany, Mehri Igci, Emine Bayraktar, Sakip Erturhan, Metin Karakok, Ahmet Arslan

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Kidney cancer is the most lethal urological cancer accounting for 3% of adult malignancies. VHL, a tumor-suppressor gene, is best known to be associated with renal cell carcinoma (RCC). The VHL functions as negative regulator of hypoxia inducible factors. Recent sequencing efforts have identified several novel frequent mutations of histone modifying and chromatin remodeling genes in ccRCC (clear cell RCC) including PBRM1 and SETD2. The PBRM1 gene encodes the BAF180 protein, which involved in transcriptional activation and repression of selected genes. SETD2 encodes a histone methyltransferase, which may play a role in suppressing tumor development. In this study, RNAs of 30 paired tumor and normal samples that were grouped according to the types of kidney cancer and clinical characteristics of patients, including gender and average age were examined by RT-PCR, SSCP and sequencing techniques. VHL, PBRM1 and SETD2 expressions were relatively down-regulated. However, statistically no significance was found (Wilcoxon signed rank test, p > 0.05). Interestingly, no mutation was observed on the contrary of previous studies. Understanding the molecular mechanisms involved in the pathogenesis of RCC has aided the development of molecular-targeted drugs for kidney cancer. Further analysis is required to identify the responsible genes rather than VHL, PBRM1 and SETD2 in kidney cancer.

Keywords: kidney cancer, molecular biomarker, expression analysis, mutation screening

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Authors: Mir Hussain Nawaz, Lyudmila Nedyalkova, Haizhong Zhu, Wael M. Rabeh

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In this study, we aim to biochemically and structurally characterize the interactions of human HK2 with the mitochondria in addition to the role of its N-terminal domain in catalysis and stability of the full-length enzyme. Here, we solved the crystal structure of human HK2 in complex with glucose and glucose-6-phosphate (PDB code: 2NZT), where it is a homodimer with catalytically active N- and C-terminal domains linked by a seven-turn α-helix. Different from the inactive N-terminal domains of isozymes 1 and 3, the N- domain of HK2 not only capable to catalyze a reaction but it is responsible for the thermodynamic stabilizes of the full-length enzyme. Deletion of first α-helix of the N-domain that binds to the mitochondria altered the stability and catalytic activity of the full-length HK2. In addition, we found the linker helix between the N- and C-terminal domains to play an important role in controlling the catalytic activity of the N-terminal domain. HK2 is a major step in the regulation of glucose metabolism in cancer making it an ideal target for the development of new anticancer therapeutics. Characterizing the structural and molecular mechanisms of human HK2 and its role in cancer metabolism will accelerate the design and development of new cancer therapeutics that are safe and cancer specific.

Keywords: cancer metabolism, enzymology, drug discovery, protein stability

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Authors: E. Wairimu Mwangi, Daniel Sarpong

Abstract:

Background: Access to effective antiretroviral therapy in the United States has resulted in the rise in longevity in people living with HIV (PLHIV). Despite the progress, women living with HIV (WLWH) experience increasing rates of cardiometabolic disorders compared with their HIV-negative counterparts. Studies focusing on the predictors of metabolic disorders in this population have largely focused on the composite measure of metabolic syndrome (METs). This study seeks to identify the predictors of composite and individual METs factors in a nationally representative sample of WLWH. In particular, the study also examines the role of food security in predicting METs. Methods: The study comprised 1800 women, a subset of participants from the Women’s Interagency HIV Study (WIHS). The primary exposure variable, food security, was measured using the U.S. 10-item Household Food Security Survey Module. The outcome measures are the five metabolic syndrome indicators (elevated blood pressure [systolic BP > 130 mmHg and diastolic BP ≥ 85 mmHg], elevated fasting glucose [≥ 110 mg/dL], elevated fasting triglyceride [≥ 150 mg/dL], reduced HDL cholesterol [< 50 mg/dL], and waist circumference > 88 cm) and the composite measure - Metabolic Syndrome (METs) Status. Each metabolic syndrome indicator was coded one if yes and 0 otherwise. The values of the five indicators were summed, and participants with a total score of 3 or greater were classified as having metabolic syndrome. Participants classified as having metabolic syndrome were assigned a code of 1 and 0 otherwise for analysis. The covariates accounted for in this study fell into sociodemographic factors and behavioral and health characteristics. Results: The participants' mean (SD) age was 47.1 (9.1) years, with 71.4% Blacks and 10.9% Whites. About a third (33.1%) had less than a high school (HS) diploma, 60.4% were married, 32.8% were employed, and 53.7% were low-income. The prevalence of worst dietary diversity, low, moderate, and high food security were 24.1%, 26.6%, 17.0%, and 56.4%, respectively. The correlate profile of the five individual METs factors plus the composite measure of METs differ significantly, with METs based on HDL having the most correlates (Age, Education, Drinking Status, Low Income, Body Mass Index, and Health Perception). Additionally, metabolic syndrome based on waist circumference was the only metabolic factor where food security was significantly correlated (Food Security, Age, and Body Mass Index). Age was a significant predictor of all five individual METs factors plus the composite METs measure. Except for METs based on Fasting Triglycerides, body mass index (BMI) was a significant correlate of the various measures of metabolic syndrome. Conclusion: High-density Lipoprotein (HDL) cholesterol significantly correlated with most predictors. BMI was a significant predictor of all METs factors except Fasting Triglycerides. Food insecurity, the primary predictor, was only significantly associated with waist circumference.

Keywords: blood pressure, food insecurity, fasting glucose, fasting triglyceride, high-density lipoprotein, metabolic syndrome, waist circumference, women living with HIV

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Authors: Barbara Zapala, Marek Dziechciowski, Olaf Chmura, Monika Piwowar, Katarzyna Gawlik, Dorota Pawlicka-Gosiewska, Krzysztof Skotniczny, Bogdan Solnica, Kazimierz Pitynski

Abstract:

BACKGROUND: Endometrial cancer is one of the most common gynecologic malignancy in developed countries.We hypothesized that amount of circulating micro-particles in blood may be connected with the development of endometrial hyperplasia and endometrial cancer. The aim of this study was to measure the micro-particles amount in uterine venous blood and in peripheral venous blood in women with atypical endometrial hyperplasia and endometrioid endometrial cancer. MATERIALS AND METHODS: By using flow cytometry (BD Canto II cytometer) we measured micro-particles amount in citrate plasma samples from peripheral and uterine venous blood of women with atypical hyperplasia of endometrium or endometrial cancer. We determined the amount of total (TF+), endothelial (CD144+) and monocytic (CD14+) micro- particles. RESULTS: Here we show statistically significant higher micro-particle levels in women with atypical hyperplasia of endometrium or endometrial cancer in comparison to healthy women. Performing measurements of the amounts of total, endothelial and monocytic microparticles allow for reliable differentiation between healthy, atypical hyperplasia and endometrial cancer groups. In blood samples from uterine veins the circulating micro-particle levels were significantly different from peripheral blood samples. The micro-particle levels in uterine blood samples were 7-fold higher than in those from peripheral blood of women with both atypical hyperplasia of endometrium and endometrial cancer when compared to the control group of healthy women. CONCLUSION: These results strongly suggested that the level of circulating micro-particles may be a sign of endometrial cancer development, however the detailed study is needed focusing on molecular processes passed through this small circulating molecules.

Keywords: endometrial cancer, endometrial hyperplasia, microvesicles, uterine blood

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Authors: T. Nalowa, L. Foncha, S. Eposi

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Prostate enlargement, prostate cancer are major global health problems affecting many men as they advance in age. It is highly recommended to encourage older men to get Prostate Specific Antigen test screening frequently. Conventional treatments like radiation, chemotherapy are associated with many side effects. And this situation is a call for concern. Traditional medicine is affordable, easily prepared with little or no side effects and it contains many phytochemicals. The study aims to find the cure for prostate cancer and prostate enlargement by extracting products from plant tissues of specific herbs to determine anti-inflammatory, anti-cancer, and anti-hematuria properties. Descriptive statistical analysis was applied to describe the data process. The commonly used method of preparation was extraction. Overall, 40 patients were classified based on their medical conditions on their underlying user report. Rural communities in Fako are rich sources of plants with medicinal properties. The used plants consequently provide basic information and aid to investigate the cure of prostate cancer and prostate enlargement, with great significance.

Keywords: cancer, enlargement, metastases, prostate

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Authors: Mohsin Ali Baloch, Saira Baloch

Abstract:

Objective: To analyze hematological changes in patients of oral cancer with history of smokable and chewable tobacco use, and to compare them with healthy controls. Study Design: Descriptive type of study survey. Setting: This study was conducted at the Department of Oral and Maxillofacial Surgery, LUMHS, Jamshoro. Study Period: One year July, 2013 to July, 2014. Subject and Methods: Histopathologically confirmed hundred cases of oral cancer with the history of smokable and non-smokable tobacco were selected to analyze the hematological variation. Inclusion Criteria: Histopathologically diagnosed patients of oral squamous cell carcinoma, with history of smokable and non-smokable tobacco. Exclusion Criteria: Patient with any systemic medically compromising problem, terminally ill patients, radio or chemotherapeutically treated patients, patients with metastasis to lungs or any distant metastasis, patients with the history of more than one well-defined etiological factor involved. Results: There were 73% patients of oral cancer reported with anemic. Significantly lower values of Hb, platelet, and higher mean values of ESR, TLC, and were observed in both groups of oral cancer patients; tobacco smokers and tobacco chewers as compared to non-smokers healthy controls. There was more decline in the level of haemoglobin and incline in the level of ESR observed in tobacco chewer oral cancer patients as compared to tobacco smokers patients, while TLC was more observed in smokers. Conclusion: Oral cancer patients with a history of chewable/smokable tobacco have likely worse hematological profile, which increases the anesthetic and surgical challenges for maxillofacial surgeons, which have a significant impact on treatment planning as well.

Keywords: oral cancer, hematological variations, tobacco, smokers

Procedia PDF Downloads 404