Search results for: cancer patient

Authors: Faraz Zarghami, Elham Anari, Nosratollah Zarghami, Yones Pilehvar-Soltanahmadi, Abolfazl Akbarzadeh, Sepideh Jalilzadeh-Tabrizi

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The development of nanotherapy has presented a new method of drug delivery targeted directly to the neoplasmic tissues, to maximize the action with fewer dose requirements. In the past two decades, poly(lactic-co-glycolic acid) (PLGA) has frequently been investigated by many researchers and is a popular polymeric candidate, due to its biocompatibility and biodegradability, exhibition of a wide range of erosion times, tunable mechanical properties, and most notably, because it is a FDA-approved polymer. Chrysin is a natural flavonoid which has been reported to have some significant biological effects on the processes of chemical defense, nitrogen fixation, inflammation, and oxidation. However, the low solubility in water decreases its bioavailability and consequently disrupts the biomedical benefits. Being loaded with PLGA-PEG increases chrysin solubility and drug tolerance, and decreases the discordant effects of the drug. The well-structured chrysin efficiently accumulates in the breast cancer cell line (T47D). In the present study, the structure and chrysin loading were delineated using proton nuclear magnetic resonance (HNMR), Fourier-transform infrared spectroscopy (FT-IR), and scanning electron microscopy (SEM), and the in vitro cytotoxicity of pure and nanochrysin was studied by the MTT assay. Next, the RNA was exploited and the cytotoxic effects of chrysin were studied by real-time PCR. In conclusion, the nanochrysin therapy developed is a novel method that could increase cytotoxicity to cancer cells without damaging the normal cells, and would be promising in breast cancer therapy.

Keywords: MTT assay, chrysin, flavonoids, nanotherapy

Procedia PDF Downloads 248

Authors: Joshua Russell, Omar Zubair, Reuben Ndegwa

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Introduction: Mesenteric ischemia is an uncommon condition that can be challenging to diagnose in the acute setting, with the potential for significant morbidity and mortality. Very rarely has acute acalculous cholecystitis been described in the setting of mesenteric ischemia. Case: This was the case in a 78-year-old male, who initially presented with clinical and radiological evidence of small bowel obstruction, thought likely secondary to malignancy. The patient had a 6-week history of anorexia, worsening lower abdominal pain, and ~30kg of unintentional weight loss over a 12-month period and a CT- scan demonstrated a transition point in the distal ileum. The patient became increasingly hemodynamically unstable and peritonitic, and an emergency laparotomy was performed. Intra-operatively, however, no obvious transition point was identified, and instead, the gallbladder was markedly gangrenous and oedematous, consistent with acalculous cholecystitis. An open total cholecystectomy was subsequently performed. The patient was admitted to the Intensive Care Unit post-operatively and continued to deteriorate over the proceeding 48 hours, with two re-look laparotomies demonstrating progressively worsening bowel ischemia, initially in the distribution of the superior mesenteric artery and then the coeliac trunk. On review, the patient was found to have an aberrant right hepatic artery arising from the superior mesenteric artery. The extent of ischemia was considered non-survivable, and the patient was palliated. Discussion: Multiple theories currently exist for the underlying pathophysiology of acalculous cholecystitis, including biliary stasis, sepsis, and ischemia. This case lends further support to ischemia as the underlying etiology of acalculous cholecystitis. This is particularly the case when considered in the context of the patient’s aberrant right hepatic artery arising from the superior mesenteric artery, which occurs in 11-14% of patients. Conclusion: This case report adds further insight to the debate surrounding the pathophysiology of acalculous cholecystitis. It also presents acalculous cholecystitis as a complication of mesenteric ischemia that should always be considered, especially in the elderly patient and in the context of relatively common anatomical variations. Furthermore, the case brings to attention the importance of maintaining dynamic working diagnoses in the setting of evolving pathophysiology and clinical presentations.

Keywords: acalculous cholecystitis, anatomical variation, general surgery, mesenteric ischemia

Procedia PDF Downloads 185

Authors: Sarocha Vivatvakin, Thanaporn Ratchataswan, Thiratest Leesutipornchai, Komkrit Ruangritchankul, Somboon Keelawat, Virachai Kerekhanjanarong, Patnarin Mahattanasakul, Saknan Bongsebandhu-Phubhakdi

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In this globalization era, much attention has been drawn to various molecular biomarkers, which may have the potential to predict the progression of cancer. Epidermal growth factor receptor (EGFR) is the classic member of the ErbB family of membrane-associated intrinsic tyrosine kinase receptors. EGFR expression was found in several organs throughout the body as its roles involve in the regulation of cell proliferation, survival, and differentiation in normal physiologic conditions. However, anomalous expression, whether over- or under-expression is believed to be the underlying mechanism of pathologic conditions, including carcinogenesis. Even though numerous discussions regarding the EGFR as a prognostic tool in head and neck cancer have been established, the consensus has not yet been met. The aims of the present study are to assess the correlation between the level of EGFR expression and demographic data as well as clinicopathological features and to evaluate the ability of EGFR as a reliable prognostic marker. Furthermore, another aim of this study is to investigate the probable pathophysiology that explains the finding results. This retrospective study included 30 squamous cell laryngeal carcinoma patients treated at King Chulalongkorn Memorial Hospital from January 1, 2000, to December 31, 2004. EGFR expression level was observed to be significantly downregulated with the progression of the laryngeal cancer stage. (one way ANOVA, p = 0.001) A statistically significant lower EGFR expression in the late stage of the disease compared to the early stage was recorded. (unpaired t-test, p = 0.041) EGFR overexpression also showed the tendency to increase recurrence of cancer (unpaired t-test, p = 0.128). A significant downregulation of EGFR expression was documented in advanced stage laryngeal cancer. The results indicated that EGFR level correlates to prognosis in term of stage progression. Thus, EGFR expression might be used as a prevailing biomarker for laryngeal squamous cell carcinoma prognostic prediction.

Keywords: downregulation, epidermal growth factor receptor, immunohistochemistry, laryngeal squamous cell carcinoma

Procedia PDF Downloads 107

Authors: Cheng-Cao Sun, Shu-Jun Li, Cuili Yang, Yongyong Xi, Liang Wang, Feng Zhang, De-Jia Li

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Hsa-miRNA-326 (miR-326) has recently been discovered having anticancer efficacy in different organs. However, the role of miR-326 on non-small cell lung cancer (NSCLC) is still ambiguous. In this study, we investigated the role of miR-326 on the development of NSCLC. The results indicated that miR-326 was significantly down-regulated in primary tumor tissues and very low levels were found in NSCLC cell lines. Ectopic expression of miR-326 in NSCLC cell lines significantly suppressed cell growth as evidenced by cell viability assay, colony formation assay and BrdU staining, through inhibition of cyclin D1, cyclin D2, CDK4, and up-regulation of p57(Kip2) and p21(Waf1/Cip1). In addition, miR-326 induced apoptosis, as indicated by concomitantly with up-regulation of key apoptosis protein cleaved caspase-3, and down-regulation of anti-apoptosis protein Bcl2. Moreover, miR-326 inhibited cellular migration and invasiveness through inhibition of matrix metalloproteinases (MMP)-7 and MMP-9. Further, oncogene CCND1 was revealed to be a putative target of miR-326, which was inversely correlated with miR-326 expression in NSCLC. Taken together, our results demonstrated that miR-326 played a pivotal role on NSCLC through inhibiting cell proliferation, migration, invasion, and promoting apoptosis by targeting oncogenic CCND1.

Keywords: hsa-miRNA-326 (miR-326), cyclin D1, non-small cell lung cancer (NSCLC), proliferation, apoptosis

Procedia PDF Downloads 301

Authors: Ditsapelo M. McFarland

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Background: Despite the availability of the Pap smear services in urban areas in Botswana, most women in such areas do not seem to screen regular for prevention of the cervical cancer disease. Reasons for non-use of the available Pap smear services are not well understood. Beliefs about cancer may influence participation in cancer screening in these women. The purpose of this study was to develop an instrument to measure beliefs about cervical cancer and Pap smear screening among Black women in Botswana, and evaluate the psychometric properties of the instrument. Significance: Instruments that are designed to measure beliefs about cervical cancer and screening among black women in Botswana, as well as in the surrounding region, are presently not available. Valid and reliable instruments are needed for exploration of the women’s beliefs about cervical cancer. Conceptual Framework: The Health Belief Model (HBM) provided a conceptual framework for the study. Methodology: The study was done in four phases: Phase 1: item generation: 15 items were generated from literature review and qualitative data for each of four conceptually defined HBM constructs: Perceived susceptibility, severity, benefits, and barriers (Version 1). Phase 2: content validity: Four experts who were advanced practice nurses of African descent and were familiar with the content and the HBM evaluated the content. Experts rated the items on a 4-point Likert scale ranging from: 1=not relevant, 2=somewhat relevant, 3=relevant and 4=very relevant. Fifty-five items were retained for instrument development: perceived susceptibility - 11, severity - 14, benefits - 15 and barriers - 15, all measuring on a 4-point Likert scale ranging from strongly disagree (1) to strongly agree (4). (Version 2). Phase 3: pilot testing: The instrument was pilot tested on a convenient sample of 30 women in Botswana and revised as needed. Phase 4: reliability: the revised instrument (Version 3) was submitted to a larger sample of women in Botswana (n=300) for reliability testing. The sample included women who were Batswana by birth and decent, were aged 30 years and above and could complete an English questionnaire. Data were collected with the assistance of trained research assistants. Major findings: confirmatory factor analysis of the 55 items found that a number of items did not adequately load in a four-factor solution. Items that exhibited reasonable reliability and had low frequency of missing values (n=36) were retained: perceived barriers (14 items), perceived benefits (8 items), perceived severity (4 items), and perceived susceptibility (10 items). confirmatory factor analysis (principle components) for a four factor solution using varimax rotation demonstrated that these four factors explained 43% of the variation in these 36 items. Conclusion: reliability analysis using Cronbach’s Alpha gave generally satisfactory results with values from 0.53 to 0.89.

Keywords: cervical cancer, factor analysis, psychometric evaluation, varimax rotation

Procedia PDF Downloads 123

Authors: Saravanan Govindaraju, Kyusik Yun

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The purpose of this study is to develop the chitosan doped curcumin gold cluster nanofiber for wound healing and skin cancer drug delivery applications. Chitosan is a typical marine polysaccharide composed of glucosamine and n-acetyl glucosamine biodegradable and biocompatible polymer. Curcumin is a natural bioactive molecule obtained from Curcuma longo, it mostly occurs in some Asian countries like India and China. It has naturally antioxidant, antimicrobial, wound healing and anticancer property. Due to this advantage, we prepared a combination of natural polymer chitosan with Curcumin and gold nanocluster nanofiber (CH-CUR-AuNCs nanofibers). The prepared nanofiber was characterized by using Fourier transform infrared spectroscopy (FT-IR), and scanning electron microscopy (SEM). Antibacterial studies were performed with E.coli and S.aureus. Antioxidant assay, drug release test, and cytotoxicity will be evaluated. Prepared nanofiber emits low intensity of red fluorescent. The FTIR confirm the presence of chitosan and Curcumin in the nanofiber. In vitro study clearly shows the antibacterial activity against the gram negative and gram positive bacteria. Particularly, synthesised nanofibers provide better antibacterial activity against gram negative than gram positive. Cytotoxicity study also provides better killing rate in cancer cell, biocompatible with normal cell. Prepared CH-CUR-AuNCs nanofibers provide the better killing rate to bacterial strains and cancer cells. Finally, prepared nanofiber can be possible to use for wound healing dressing, patch for skin cancer and other biomedical applications.

Keywords: curcumin, chitosan, gold clusters, nanofibers

Procedia PDF Downloads 256

Authors: Yifat Koren Carmi, Abed Agbarya, Hazem Khamaisi, Raymond Farah, Yelena Shechtman, Roman Korobochka, Jacob Gopas, Jamal Mahajna

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Ovarian cancer (OC), the second most common form of gynecological malignancy, has a poor prognosis and is frequently identified in its late stages. The recommended treatment for OC typically includes a platinum-based chemotherapy, like carboplatin. Nonetheless, OC treatment has proven challenging due to toxicity and development of acquired resistance to therapy. Chemoresistance is a significant obstacle to a long-lasting response in OC patients, believed to arise from alterations within the cancer cells as well as within the tumor microenvironments (TME). Malignant ascites is a presenting feature in more than one-third of OC patients. It serves as a reservoir for a complex mixture of soluble factors, metabolites, and cellular components, providing a pro-inflammatory and tumor-promoting microenvironment for the OC cells. Malignant ascites is also associated with metastasis and chemoresistance. In an attempt to elucidate the role of TME in chemoresistance of OC, we monitored the ability of soluble factors derived from ascites fluids to affect platinum sensitivity of OC cells. This research, compared ascites fluids from non-malignant cirrhotic patients to those from OC patients in terms of their ability to alter the platinum sensitivity of OC cells. Our findings indicated that exposure to OC ascites induces platinum chemoresistance on OC cells in 11 out of 13 cases (85%). In contrast, 75% of cirrhosis ascites (3 out of 4) failed to confer platinum chemoresistance to OC cells. Cytokine array analysis revealed that IL-6, and to a lesser extent HGF were enriched in OC ascites, whereas IL-22 was enriched in cirrhosis ascites. Pharmaceutical inhibitors that target the IL-6/JAK signaling pathway were mildly effective in overcoming the platinum chemoresistance induced by malignant ascites. In contrast, Crizotinib an HGF/c-MET inhibitor, and 2-hydroxyestradiol (2HE2) were effective in restoring platinum chemoresistance to OC. Our findings demonstrate the importance of OC ascites in supporting platinum chemoresistance as well as the potential of a combination therapy with Crizotinib and the estradiol metabolite 2HE2 to regain OC cells chemosensitivity.

Keywords: ovarian cancer, platinum chemoresistance, malignant ascites, tumor microenvironment, IL-6, 2-hydroxyestradiol, HGF, crizotinib

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Authors: Pintusorn Hansakul, Ruchilak Rattarom, Arunporn Itharat

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Background: Benjakul, a Thai traditional herbal formulation, comprises of five plants: Piper chaba, Piper sarmentosum, Piper interruptum, Plumbago indica, and Zingiber officinale. It has been widely used to treat cancer patients in the context of folk medicine in Thailand. This study aimed to investigate the cytotoxic effect of the ethanol extract of Benjakul against three non-small cell lung cancer (NSCLC) cell lines (NCI-H226, A549, COR-L23), small cell lung cancer (SCLC) cell line NCI-H1688 and normal lung fibroblast cell line MRC-5. The study further examined the molecular mechanisms underlying its cytotoxicity via induction of apoptosis in NCI-H226 cells. Methods: The cytotoxic effect of Benjakul was determined by SRB assay. The effect of Benjakul on cell cycle distribution was assessed by flow cytometric analysis. The apoptotic effects of Benjakul were determined by sub-G1 quantitation and Annexin V-FITC/PI flow cytometric analyses as well as by changes in caspase-3 activity. Results: Benjakul exerted potent cytotoxicity on NCI-H226 and A549 cells but lower cytotoxicity on COR-L23 and NCI-H1688 cells without any cytotoxic effect on normal cells. Molecular studies showed that Benjakul extract induced G2/M phase arrest in human NCI-H226 cells in a dose-dependent manner. The highest concentration of Benjakul (150 μg/ml) led to the highest increase in the G2/M population at 12 h, followed by the highest increase in the sub-G1 population (apoptotic cells) at 60 h. Benjakul extract also induced early apoptosis (AnnexinV +/PI−) in NCI-H226 cells in a dose- and time- dependent manner. Moreover, treatment with 150 μg/ml Benjakul extract for 36 h markedly increased caspase-3 activity by 3.5-fold, and pretreatment with the general caspase inhibitor z-VAD-fmk completely abolished such activity. Conclusions: This study reveals for the first time the regulation of apoptosis in human lung cancer NCI-H226 cells through caspase-dependent mechanism by Benjakul extract.

Keywords: apoptosis, Benjakul, caspase activation, cytotoxicity

Procedia PDF Downloads 434

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

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

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

Procedia PDF Downloads 443

Authors: Claudia Norambuena, Myissa Weiss, Maria Ruiz Maya, Matthew Straley, Elijah Hammond, Benjamin Chesebrough, David Grow

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The purpose of this project is to develop a low-cost, portable sensor device that can be used at home for long-term analysis of gait and balance abnormalities. One area of particular concern involves the asymmetries in movement and balance that can accompany certain types of injuries and/or the associated devices used in the repair and rehabilitation process (e.g. the use of splints and casts) which can often increase chances of falls and additional injuries. This device has the capacity to monitor a patient during the rehabilitation process after injury or operation, increasing the patient’s access to healthcare while decreasing the number of visits to the patient’s clinician. The sensor device may thereby improve the quality of the patient’s care, particularly in rural areas where access to the clinician could be limited, while simultaneously decreasing the overall cost associated with the patient’s care. The device consists of nine interconnected accelerometer/ gyroscope/compass chips (9-DOF IMU, Adafruit, New York, NY). The sensors attach to and are used to determine the orientation and acceleration of the patient’s lower abdomen, C7 vertebra (lower neck), L1 vertebra (middle back), anterior side of each thigh and tibia, and dorsal side of each foot. In addition, pressure sensors are embedded in shoe inserts with one sensor (ESS301, Tekscan, Boston, MA) beneath the heel and three sensors (Interlink 402, Interlink Electronics, Westlake Village, CA) beneath the metatarsal bones of each foot. These sensors measure the distribution of the weight applied to each foot as well as stride duration. A small microntroller (Arduino Mega, Arduino, Ivrea, Italy) is used to collect data from these sensors in a CSV file. MATLAB is then used to analyze the data and output the hip, knee, ankle, and trunk angles projected on the sagittal plane. An open-source program Processing is then used to generate an animation of the patient’s gait. The accuracy of the sensors was validated through comparison to goniometric measurements (±2° error). The sensor device was also shown to have sufficient sensitivity to observe various gait abnormalities. Several patients used the sensor device, and the data collected from each represented the patient’s movements. Further, the sensors were found to have the ability to observe gait abnormalities caused by the addition of a small amount of weight (4.5 - 9.1 kg) to one side of the patient. The user-friendly interface and portability of the sensor device will help to construct a bridge between patients and their clinicians with fewer necessary inpatient visits.

Keywords: biomedical sensing, gait analysis, outpatient, rehabilitation

Procedia PDF Downloads 282

Authors: Ihtisham Bukhari

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In the current study, we enrolled a 46, XY phenotypically female patient bearing testes in her inguinal canal. DNA sequencing of the AR gene detected a missense mutation C.1715A > G (p. Y572C) in exon 2 which is already known to cause Complete androgen insensitivity syndrome (CAIS). We further studied the effects of this mutation on the testicular histopathology of the patient. No spermatocytes were seen in the surface spreading of testicular tissues while H&E staining showed that seminiferous tubules predominantly have only Sertoli cells. To confirm this meiotic failure is likely due to the current AR mutation we performed mRNA expression of genes associated with AR pathway, expression and location of the associated proteins in testicular tissues. Western blot and real-time PCR data showed that the patient had high levels of expression of AMH, SOX9, and INNB in testis. Tubules were stained with SOX9 and AMH which revealed Sertoli cell maturation arrest. Therefore, we suggest that AR mutation enhances AMH expression which ultimately leads to failure in the maturation of Sertoli cells and failure in spermatogenesis.

Keywords: androgen receptor, spermatogenesis, infertility, Sertoli cell only syndrome

Procedia PDF Downloads 139

Authors: Rachel Matar, Maxime Merheb

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Chemical drugs have been used for many centuries as the only way to cure diseases until the novel gene therapy has been created in 1960. Gene therapy is based on the insertion, correction, or inactivation of genes to treat people with genetic illness (1). Gene therapy has made wonders in Parkison’s, Alzheimer and multiple sclerosis. In addition to great promises in the healing of deadly diseases like many types of cancer and autoimmune diseases (2). This method implies the use of recombinant DNA technology with the help of different viral and non-viral vectors (3). It is nowadays used in somatic cells as well as embryos and gametes. Beside all the benefits of gene therapy, this technique is deemed by some opponents as an ethically unacceptable treatment as it implies playing with the genes of living organisms.

Keywords: gene therapy, genetic disease, cancer, multiple sclerosis

Procedia PDF Downloads 537

Authors: Ali Showail Ali Alasmari

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Introduction: Cataract is the loss of transparency of the lens inside the eye. It is the most common cause of visual loss and blindness worldwide. This study provides a systemic review of the recent findings on the association of vitamin D, and vitamin B12, and their possible role in preventing cataracts in senile (S) and diabetic mellitus (DM) patient groups. Objective: This study was intended to establish and investigate if there is any role between vitamin D and vitamin B12? Secondly, the connection between serum level of vitamin D and vitamin B12 in cataract incidence senile (s) vs. diabetic mellitus (DM) cataract patient groups. Furthermore, to evaluate and analyze cataract occurrence regarding vitamin D and vitamin B12 levels with other risk factors. Finally, to evaluate lens opacities pre and post treatment with vitamin D and vitaminB12 linked to age and visual acuity loss in both senile(S) and diabetic mellitus (DM) cataract patients’ groups. Methods: This study conducted at the ophthalmology clinic at Muhyail General Hospital. Select a prospective case-control to study the effect of vitamin D and Vit B12 on senile(S) cataracts that caused by age and diabetic mellitus (DM)cataract patients; then we compare these two groups. This study prospectively enrolled a total of 50 samples, 25 with senile cataract and 25 with diabetic cataract, from ophthalmology clinic at Muhyail General Hospital. Measuring 25-hydroxy vitamin D and vitamin B12 level concentrations in the assigned samples. Analyses were performed using SAS (statistical analysis software) program. Results: The most important finding in this study was that the senile(s) cataract patients’ group greatly benefited by the combination therapy of vitamin D, and Vitamin B12 reached (28.5±1.50 and 521.1±21.10) respectively; on the contrary, the diabetic cataract patient group hardly shows any significant improvement (21.5 ± 1.00 and 197.2 ± 7.20) respectively. This is because of the Metformin, the first line drug for treating diabetes, has been reported to potentially decrease vitamin B-12 status. This epigenetic modification was correlated with the diabetic mellitus (DM) cataract patients’ group not responding. Vitamin B12 deficiency also leads to an impairment of the conversion of methylmalonyl-CoA to succinyl-CoA, which has been associated with insulin resistance. There was no significant difference between the age, body mass index (BMI), the mean of Vit-D pre-treatments, and the mean values of Hemoglobin A1C of both senile (S) and diabetic mellitus (DM) cataract patient groups. On other hand, there was a highly significant difference between the mean values of glucose levels in both senile (S) and diabetic mellitus (DM) cataract patient groups. Conclusion: Here we conclude that diabetic mellitus (DM) cataract patient group hardly benefited from this combination therapy vitamin D and vitamin B12; on the other hand senile patient group (s) benefited a lot from the therapy.

Keywords: cataract patients, senile, diabetes mellitus, vitamin B12, vitamin D, Muhyail General Hospital, Saudi Arabia

Procedia PDF Downloads 102

Authors: K. Shaloom Mbambu, M. Pascal Tshimbalanga, K. Ruth Mutala, K. Roger Kabuya, N. Dieudonné Kabeya, Y. L. Kabeya Mukeba

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In this article, the authors examine the even more worrying situation of girls in sub-Saharan Africa. Two-girls on five are private of Global Education, which represents a real loss to the development of communities and countries. Cultural traditions, poverty, violence, early and forced marriages, early pregnancies, and many other gender inequalities were the causes of this cancer development. Namely, "it is no more efficient development tool that is educating girls." The non-schooling of girls and their lack of supervision by liberal professions have serious consequences for the life of each of them. To improve the conditions of their inferior status, girls to men introduce poverty and health risks. Raising awareness among parents and communities on the importance of girls' education, improving children's access to school, girl-boy equality with their rights, creating income, and generating activities for girls, girls, and girls learning of liberal trades to make them self-sufficient. Organizations such as the United Nations Organization can save the children. ASEAD and the AEDA group are predicting the impact of this cancer on the development of a nation's future generation must be preserved.

Keywords: young girl, Sub-Saharan Africa, higher and vocational education, development, society, environment

Procedia PDF Downloads 251

Authors: Sonia Mahajan Dinesh, Anant Dinesh, Madhavi Tripathi, Vinod Kumar Ramteke, Rajnish Sharma, Anupam Mondal

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Background: Neo-adjuvant chemotherapy plays an important role in treatment of breast cancer by decreasing the tumour load and it offers an opportunity to evaluate response of primary tumour to chemotherapy. Standard anatomical imaging modalities are unable to accurately reflect the response to chemotherapy until several cycles of drug treatment have been completed. Metabolic imaging using tracers like 18F-fluorodeoxyglucose (FDG) as a marker of glucose metabolism or amino acid tracers like L-methyl-11C methionine (MET) have potential role for the measurement of treatment response. In this study, our objective was to compare these two PET tracers for assessment of response to neoadjuvant chemotherapy, in locally advanced breast carcinoma. Methods: In our prospective study, 20 female patients with histology proven locally advanced breast carcinoma underwent PET-CT imaging using FDG and MET before and after three cycles of neoadjuvant chemotherapy (CAF regimen). Thereafter, all patients were taken for MRM and the resected specimen was sent for histo-pathological analysis. Tumour response to the neoadjuvant chemotherapy was evaluated by PET-CT imaging using PERCIST criteria and correlated with histological results. Responses calculated were compared for statistical significance using paired t- test. Results: Mean SUVmax for primary lesion in FDG PET and MET PET was 15.88±11.12 and 5.01±2.14 respectively (p<0.001) and for axillary lymph nodes was 7.61±7.31 and 2.75±2.27 respectively (p=0.001). Statistically significant response in primary tumour and axilla was noted on both FDG and MET PET after three cycles of NAC. Complete response in primary tumour was seen in only 1 patient in FDG and 7 patients in MET PET (p=0.001) whereas there was no histological complete resolution of tumor in any patient. Response to therapy in axillary nodes noted on both PET scans were similar (p=0.45) and correlated well with histological findings. Conclusions: For the primary breast tumour, FDG PET has a higher sensitivity and accuracy than MET PET and for axilla both have comparable sensitivity and specificity. FDG PET shows higher target to background ratios so response is better predicted for primary breast tumour and axilla. Also, FDG-PET is widely available and has the advantage of a whole body evaluation in one study.

Keywords: 11C-methionine, 18F-FDG, breast carcinoma, neoadjuvant chemotherapy

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Authors: Hyunsik Park

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As the rate of cerebrovascular disease increases in old populations, the prevalence rate of vascular dementia would be expected. Therefore, authors designed this study to find out the possibility of somatosensory evoked potentials(SSEP) as a parameter for early diagnosis and prognosis prediction of vascular dementia in cortical vascular dementia patients. 21 patients who met the criteria for vascular dementia according to DSM-IV,ICD-10and NINDS-AIREN with the history of recent cognitive impairment, fluctuation progression, and neurologic deficit. We subdivided these patients into two groups; a mild dementia and a severe dementia groups by MMSE and CDR score; and analysed comparison between normal control group and patient control group who have been cerebrovascular attack(CVA) history without dementia by using N20 latency and amplitude of median nerve. In this study, mild dementia group showed significant differences on latency and amplitude with normal control group(p-value<0.05) except patient control group(p-value>0.05). Severe dementia group showed significant differences both normal control group and patient control group.(p-value<0.05, <001). Since no significant difference has founded between mild dementia group and patient control group, SSEP has limitation to use for early diagnosis test. However, the comparison between severe dementia group and others showed significant results which indicate SSEP can predict the prognosis of vascular dementia in cortical vascular dementia patients.

Keywords: SSEP, cortical vascular dementia, N20 latency, N20 amplitude

Procedia PDF Downloads 300

Authors: Wendu Pang, Yaxin Luo, Junhong Li, Yu Zhao, Danni Cheng, Yufang Rao, Minzi Mao, Ke Qiu, Yijun Dong, Fei Chen, Jun Liu, Jian Zou, Haiyang Wang, Wei Xu, Jianjun Ren

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We aimed to compare the prognostic prediction value of positive lymph node number (PLNN) to the American Joint Committee on Cancer (AJCC) tumor, lymph node, and metastasis (TNM) staging system for patients with hypopharyngeal squamous cell carcinoma (HPSCC). A total of 826 patients with HPSCC from the Surveillance, Epidemiology, and End Results database (2004–2015) were identified and split into two independent cohorts: training (n=461) and validation (n=365). Univariate and multivariate Cox regression analyses were used to evaluate the prognostic effects of PLNN in patients with HPSCC. We further applied six Cox regression models to compare the survival predictive values of the PLNN and AJCC TNM staging system. PLNN showed a significant association with overall survival (OS) and cancer-specific survival (CSS) (P < 0.001) in both univariate and multivariable analyses, and was divided into three groups (PLNN 0, PLNN 1-5, and PLNN>5). In the training cohort, multivariate analysis revealed that the increased PLNN of HPSCC gave rise to significantly poor OS and CSS after adjusting for age, sex, tumor size, and cancer stage; this trend was also verified by the validation cohort. Additionally, the survival model incorporating a composite of PLNN and TNM classification (C-index, 0.705, 0.734) performed better than the PLNN and AJCC TNM models. PLNN can serve as a powerful survival predictor for patients with HPSCC and is a surrogate supplement for cancer staging systems.

Keywords: hypopharyngeal squamous cell carcinoma, positive lymph nodes number, prognosis, prediction models, survival predictive values

Procedia PDF Downloads 150

Authors: Charles Lee

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The Principal Orthogonal Decomposition (POD) technique has been used as a model reduction tool for many applications in engineering and science. In principle, one begins with an ensemble of data, called snapshots, collected from an experiment or laboratory results. The beauty of the POD technique is that when applied, the entire data set can be represented by the smallest number of orthogonal basis elements. It is the such capability that allows us to reduce the complexity and dimensions of many physical applications. Mathematical formulations and numerical schemes for the POD method will be discussed along with applications in NASA’s Deep Space Large Antenna Arrays, Satellite Image Reconstruction, Cancer Detection with DNA Microarray Data, Maximizing Stock Return, and Medical Imaging.

Keywords: reduced-order methods, principal component analysis, cancer detection, image reconstruction, stock portfolios

Procedia PDF Downloads 79

Authors: B. González-Yebra, B. Flores-Nieto, P. Aguilar-Salinas, M. Preciado Puga, A. L. González Yebra

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The monitoring of populations occupationally exposed to organic solvents has been an important issue for several shoe factories for years since the International Agency for Research on Cancer (IARC) has advised on the potential carcinogenic risk of chemicals related to occupations. In order to detect if exposition to organic solvents used in some Mexican shoe factories contributes to oral carcinogenesis, we performed monitoring in three factories. Occupational exposure was determined by using monitors 3M. Organic solvents were assessed by gas chromatography. Then, we recruited 30 shoe workers (30.2 ± 8.4 years) and 10 unexposed subjects (43.3 ± 11.2 years) for the micronuclei (MN) test and immunodetection of some cancer biomarkers (ki-67, p16, caspase-3) in scraped oral epithelial cells. Monitored solvents detected were acetone, benzene, hexane, methyl ethyl ketone, and toluene in acceptable levels according to Official Mexican Norm. We found by MN test higher incidence of nuclear abnormalities (karyorrhexis, pycnosis, karyolysis, condensed chromatin, and macronuclei) in the exposed group than the non-exposed group. On the other hand, we found, a negative expression for Ki-67 and p16 in exfoliated epithelial cells from exposed and non-exposed to organic solvents subjects. Only caspase-3 shown positive patter of expression in 9/30 (30%) exposed subjects, and we detected high karyolysis incidence in caspase-3 subjects (p = 0.021). The absence of expression of proliferation markers p16 and ki-67 and presence of apoptosis marker caspase-3 are indicating the absence of malignancy in oral epithelial cells and low risk for oral cancer. It is a fact that the MN test is a very effective method to detect nuclear abnormalities in exfoliated buccal cells from subjects that have been exposed to organic solvents in the shoe industry. However, in order to improve this tool and predict cancer risk is it is mandatory to implement complementary tests as other biomarkers that can help to detect malignancy in individuals occupationally exposed.

Keywords: biomarkers, oral cancer, organic solvents, shoe industries

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Authors: Maha Soltan, Amal Z. Hassan, Howaida I. Abd-Alla, Atef G. Hanna

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Two naturally known cardenolides; acovenoside A and acobioside A were isolated from the Egyptian cultivar; Acokanthera spectabilis leaves. It is an ornamental and poisonous plant that has been traditionally claimed for their medicinal properties against infectious microbes, killing worms and curing some inflammations at little amounts. We examined the growth inhibition effects of both cardenolides against four types of human cancer cell lines using Sulphorhodamine B assay. In addition, the clonogenic assay was also performed for testing the growth inhibiting power of the isolated compounds. An in vitro mechanistic investigation was further accomplished against hepatocellular carcinoma HepG2 cell line. Microscopic examination, colorimetric ELISA and flow cytometry techniques were our tools of proving at least part of the anticancer pathway of the tested compounds. Both compounds were able to inhibit the growth of 4 human cancer cell lines at less than 100 nM. In addition, they were able to activate the executioner Caspase-3 and apoptosis was then induced as a consequence of cell growth arrest at G2/M. An attention must be payed to those bioactive agents particularly when giving their activity against cancer cells at considerable small values while presenting safe therapeutic margins as indicated by literature.

Keywords: anticancer, cardenolides, Caspase-3, apoptosis

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Authors: V. K. Srivastava

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The chemistry of compounds containing transition metals bound to sulfur containing ligands has been actively studied. Interest in these compounds arises from the identification of the biological importance of iron-sulfur containing proteins as well as the unusual behaviour of several types of synthetic metal-sulfur complexes. Metal complexes (C₆H₅)₄P)₂ Pt(Mos₄)₂, (C₆H₅)₄P)₂ Pd(MoS₄)₂, (C₆H₅)₄P)₂ Ni(MoS₄)₂ of bioinorganic relevance were investigated. The complexes [M(M'S₄)₂]²⁻ were prepared with high yield and purity as salts of the variety of organic cations. The diamagnetism and spectroscopic properties of these complexes confirmed that their structures are essentially equivalent with two bidentate M'S₄²⁻ ligands coordinated to the central d⁸ metal in a square planer geometry. The interaction of the complexes with CT-DNA was studied. Results showed that metal complexes increased DNA's relative viscosity and quench the fluorescence intensity of EB bound to DNA. In antimicrobial activities, all complexes showed good antimicrobial activity higher than ligand against gram positive, gram negative bacteria and fungi. The antitumor properties have been tested in vitro against two tumor human cell lines, Hela (derived from cervical cancer) and MCF-7 (derived from breast cancer) using metabolic activity tests. Result showed that the complexes are promising chemotherapeutic alternatives in the search of anticancer agents.

Keywords: anti cancer, biocidal, DNA binding, spectra

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Authors: A. Monika, Manu Sharma, Hong Boo Lee, Richa Dhingra, Neelima Dhingra

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Nuclear factor-κappa B serve as a molecular lynchpin that links persistent infections and chronic inflammation to increased cancer risk. Inflammation has been recognized as a hallmark and cause of cancer. Natural products present a privileged source of inspiration for chemical probe and drug design. Herbal remedies were the first medicines used by humans due to the many pharmacologically active secondary metabolites produced by plants. Some of the metabolites like Lantadene (pentacyclic triterpenoids) from the weed Lantana camara has been known to inhibit cell division and showed anti-antitumor potential. The C-3 aromatic esters of lantadenes were synthesized, characterized and evaluated for cytotoxicity and inhibitory potential against Tumor necrosis factor alpha-induced activation of Nuclear factor-κappa B in lung cancer cell line A549. The 3-methoxybenzoyloxy substituted lead analogue inhibited kinase activity of the inhibitor of nuclear factor-kappa B kinase in a single-digit micromolar concentration. At the same time, the lead compound showed promising cytotoxicity against A549 lung cancer cells with IC50 ( half maximal inhibitory concentration) of 0.98l µM. Further, molecular docking of 3-methoxybenzoyloxy substituted analogue against Inhibitor of nuclear factor-kappa B kinase (Protein data bank ID: 3QA8) showed hydrogen bonding interaction involving oxygen atom of 3-methoxybenzoyloxy with the Arginine-31 and Glutamine-110. Encouraging results indicate the Lantadene’s potential to be developed as anticancer agents.

Keywords: anticancer, lantadenes, pentacyclic triterpenoids, weed

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Authors: Amir Seyfoori, Ehsan Samiei, Mohsen Akbari

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The use of microtechnology for detection and high yield isolation of circulating tumor cells (CTCs) has shown enormous promise as an indication of clinical metastasis prognosis and cancer treatment monitoring. The Immunomagnetic assay has been also coupled to microtechnology to improve the selectivity and efficiency of the current methods of cancer biomarker isolation. In this way, generation and configuration of the local high gradient magnetic field play essential roles in such assay. Additionally, considering the intrinsic heterogeneity of cancer cells, real-time analysis of isolated cells is necessary to characterize their responses to therapy. Totally, on-chip isolation and monitoring of the specific tumor cells is considered as a pressing need in the way of modified cancer therapy. To address these challenges, we have developed a bi-layer magnetic-based microfluidic chip for enhanced CTC detection and capturing. Micromagnet arrays at the bottom layer of the chip were fabricated using a new method of magnetic nanoparticle paste deposition so that they were arranged at the center of the chain microchannel with the lowest fluid velocity zone. Breast cancer cells labelled with EPCAM-conjugated smart microgels were immobilized on the tip of the micromagnets with greater localized magnetic field and stronger cell-micromagnet interaction. Considering different magnetic nano-powder usage (MnFe2O4 & gamma-Fe2O3) and micromagnet shapes (ellipsoidal & arrow), the capture efficiency of the systems was adjusted while the higher CTC capture efficiency was acquired for MnFe2O4 arrow micromagnet as around 95.5%. As a proof of concept of on-chip tumor cell monitoring, magnetic smart microgels made of thermo-responsive poly N-isopropylacrylamide-co-acrylic acid (PNIPAM-AA) composition were used for both purposes of targeted cell capturing as well as cell monitoring using antibody conjugation and fluorescent dye loading at the same time. In this regard, magnetic microgels were successfully used as cell tracker after isolation process so that by raising the temperature up to 37⁰ C, they released the contained dye and stained the targeted cell just after capturing. This microfluidic device was able to provide a platform for detection, isolation and efficient real-time analysis of specific CTCs in the liquid biopsy of breast cancer patients.

Keywords: circulating tumor cells, microfluidic, immunomagnetic, cell isolation

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Authors: John Hang Leung, Shyh-Yau Wang, Hei-Tung Yip, Fion, Ho Tsung-chin, Agnes LF Chan

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Objectives: Platinum-resistant ovarian cancer has a short overall survival of 9–12 months and limited treatment options. The combination of immunotherapy and targeted therapy appears to be a promising treatment option for patients with ovarian cancer, particularly to patients with platinum-resistant recurrent ovarian cancer (PRrOC). However, there are no direct head-to-head clinical trials comparing their efficacy and toxicity. We, therefore, used a network to directly and indirectly compare seven newer immunotherapies or targeted therapies combined with chemotherapy in platinum-resistant relapsed ovarian cancer, including antibody-drug conjugates, PD-1 (Programmed death-1) and PD-L1 (Programmed death-ligand 1), PARP (Poly ADP-ribose polymerase) inhibitors, TKIs (Tyrosine kinase inhibitors), and antiangiogenic agents. Methods: We searched PubMed (Public/Publisher MEDLINE), EMBASE (Excerpta Medica Database), and the Cochrane Library electronic databases for phase II and III trials involving PRrOC patients treated with immunotherapy or targeted therapy plus chemotherapy. The quality of included trials was assessed using the GRADE method. The primary outcomes compared were progression-free survival, the secondary outcomes were overall survival and safety. Results: Seven randomized controlled trials involving a total of 2058 PRrOC patients were included in this analysis. Bevacizumab plus chemotherapy showed statistically significant differences in PFS (Progression-free survival) but not OS (Overall survival) for all interested targets and immunotherapy regimens; however, according to the heatmap analysis, bevacizumab plus chemotherapy had a statistically significant risk of ≥grade 3 SAEs (Severe adverse effects), particularly hematological severe adverse events (neutropenia, anemia, leukopenia, and thrombocytopenia). Conclusions: Bevacizumab plus chemotherapy resulted in better PFS as compared with all interested regimens for the treatment of PRrOC. However, statistical differences in SAEs as bevacizumab plus chemotherapy is associated with a greater risk for hematological SAE.

Keywords: platinum-resistant recurrent ovarian cancer, network meta-analysis, immune checkpoint inhibitors, target therapy, antiangiogenic agents

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Authors: Esra Cansever Mutlu, Muge Sennaroglu Bostan, Fatemeh Bahadori, Ebru Toksoy Oner, Mehmet S. Eroglu

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Paclitaxel is used in treatment of different cancer types mainly breast, ovarian, lung and Kaposi’s sarcoma. It is poorly soluble in water; therefore, currently used formulations tremendously show side-effects and high toxicity. Encapsulation of the drug in a nano drug carrier which causes both reducing side effects and increasing drug activity is a desired new approach for the nano-medicine to target the site of cancer. In this study, synthesis of a novel nano paclitaxel formulation made of a new amphiphilic monomer was followed by the investigation of its pharmacological properties. UV radical polymerization was carried out by using the monomer Lecithin-2-Acrylamido-2-methylpropane (L-AMPS) and the drug-spacer, to obtain sterically high stabilized, biocompatible and biodegradable phospholipid nanoparticles, in which the drug paclitaxel (Pxl) was encapsulated (NanoPxl). Particles showed high drug loading capacity (68%) and also hydrodynamic size less than 200 nm with slight negative surface charge. The drug release profile was obtained and in vitro cytotoxicity test was performed on MCF-7 cell line. Consequently, these data indicated that paclitaxel loaded Lecithin-AMPS/PCL-MAC nanoparticles can be considered as a new, safe and effective nanocarrier for the treatment of breast cancer.

Keywords: paclitaxel, nanoparticle, drug delivery, L-AMPS

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

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

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

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Authors: Antonio Montes, Antonio Cozar, Clara Pereyra, Diego Valor, Enrique Martinez de la Ossa

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Tissues and organs can be damaged because of traumatism, congenital illnesses, or cancer and the traditional therapeutic alternatives, such as surgery, cannot usually completely repair the damaged tissues. Tissue engineering allows regeneration of the patient's tissues, reducing the problems caused by the traditional methods. Scaffolds, polymeric structures with interconnected porosity, can be promoted the proliferation and adhesion of the patient’s cells in the damaged area. Furthermore, by means of impregnation of the scaffold with beneficial active substances, tissue regeneration can be induced through a drug delivery process. The objective of the work is the fabrication of a PVA scaffold coated with Gallic Acid and polypyrrole through a one-step foaming and impregnation process using the SSI technique (Supercritical Solvent Impregnation). In this technique, supercritical CO₂ penetrates into the polymer chains producing the plasticization of the polymer. In the depressurization step a CO₂ cellular nucleation and growing to take place to an interconnected porous structure of the polymer. The foaming process using supercritical CO₂ as solvent and expansion agent presents advantages compared to the traditional scaffolds’ fabrication methods, such as the polymer’s high solubility in the solvent or the possibility of carrying out the process at a low temperature, avoiding the inactivation of the active substance. In this sense, the supercritical CO₂ avoids the use of organic solvents and reduces the solvent residues in the final product. Moreover, this process does not require long processing time that could cause the stratification of substance inside the scaffold reducing the therapeutic efficiency of the formulation. An experimental design has been carried out to optimize the SSI technique operating conditions, as well as a study of the morphological characteristics of the scaffold for its use in tissue engineerings, such as porosity, conductivity or the release profiles of the active substance. It has been proved that the obtained scaffolds are partially porous, conductors of electricity and are able to release Gallic Acid in the long term.

Keywords: scaffold, foaming, supercritical, PVA, polypyrrole, gallic acid

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Authors: Priya Patel, Paresh Patel, Mihir Raval

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Silibinin, a flavanone as an antimicrotubular agent used in the treatment of cancer, was encapsulated in nanoparticles (NPs) of poly (lactide-co-glycolide) (PLGA) polymer using the spray-drying technique. The effects of various experimental parameters were optimized by box-behnken experimental design. Production yield, encapsulation efficiency and dissolution study along with characterization by scanning electron microscopy, DSC, FTIR followed by bioavailability study. Particle size and zeta potential were evaluated by using zetatrac particle size analyzer. Experimental design it was evaluated that inlet temperature and polymer concentration influence on the drug release. Feed flow rate impact on particle size. Results showed that spray drying technique yield 149 nm indicate nanosize range. The small size of the nanoparticle resulted in an enhanced cellular entry and greater bioavailability. Entrapment efficiency was found between 89.35% and 98.36%. Zeta potential shows good stability index of nanoparticle formulation. The in vitro release studies indicated the silibinin loaded PLGA nanoparticles provide controlled drug release over a period of 32 h. Pharmacokinetic studies demonstrated that after oral administration of silibinin-loaded PLGA nanoparticles to rats at a dose of 10 mg/kg, relative bioavailability was enhanced about 8.85-fold, compared to silibinin suspension as control hence, this investigation demonstrated the potential of the experimental design in understanding the effect of the formulation variables on the quality of silibinin loaded PLGA nanoparticles. These results describe an effective strategy of silibinin loaded PLGA nanoparticles and might provide a promising approach against the cancer.

Keywords: silibinin, cancer, nanoparticles, PLGA, bioavailability

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Authors: Renee Fabian, Jordan Davidson

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Current research on non-suicidal self-injury (NSSI) provides ample insights on best practices for caregivers and clinicians to address and reduce NSSI behavior among adolescents. However, the efficacy of evidenced-based NSSI interventions and their delivery from the perspective of adolescent patients does not receive significant attention, creating a gap between the efficacy of research-based NSSI interventions and adolescent perceptions of NSSI treatment and adolescent willingness to engage in NSSI interventions. To address the gap between practice and patient perspectives and inform more effective treatment outcomes, the current survey aims to identify major patient-reported adverse reactions to NSSI disclosures from caregivers, treating mental health clinicians, and medical professionals using a mixed methods survey of 2,500 people with a history of NSSI completed by editors at a consumer-facing health publication. Based on the analyzed results of the survey, a majority of adolescents with a history of NSSI found parents and caregivers ineffective at empathetically addressing NSSI, and a significant number of participants reported at least one treating mental health professional inadequately responded to NSSI behaviors, in addition to other findings of adverse reactions to NSSI disclosures that serve as a barrier to treatment. NSSI is a significant risk factor for future suicide attempts. Addressing patient-reported adverse reactions to NSSI disclosures in the adolescent population can remove barriers to the effectiveness of caregiver and clinician NSSI interventions and reduce the risk of NSSI-related harm and lower the risk of future suicide attempts or completions.

Keywords: adolescent self-injury, non-suicidal self-injury, patient perspectives, self-harm interventions

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Authors: Azhar Jabareen, Mahmoud Huleihel

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BRCA-1 is a multifunctional tumor suppressor, whose expression is activated by the estrogen (E2)-liganded ERα receptor. The activated ERα is a transcriptional factor which activates various genes either by direct binding to the DNA at E2-responsive elements (EREs) and indirectly associated with a range of alternative non-ERE elements. Interference with BRCA-1 expression and/or functions leads to high risk of breast or/and ovarian cancer. Our lab investigated the involvement of Human T-cell leukemia Virus Type 1 (HTLV-1) in breast cancer, since HTLV-1 Tax was found to strongly inhibit BRCA-1 expression. In addition, long exposure of 12-O-tetradecanoylphorbol-13-acetate (TPA), which is one of the stress-inducing agents activated the HTLV-1 promoter. So here the involvement of TPA in breast cancer had been examined by testing the effect of TPA on BRCA-1 and ERE expression. The results showed that TPA activated both BRCA-1 and ERE expression. In the 12 hours TPA activated the tow promoters more than others time, and after 24 hours the level of the tow promoters was decreased. Tax inhibited BRCA-1 expression but did not succeed to inhibit the effect of TPA. Then the activation of the two promoters was not through ERα pathway because TPA had no effect on ERα binding to the two promoters of the BRCA-1 and ERE. Also, the activation was not via nuclear factor kappa B (NF-κB) pathway because when the inhibitory of NF-κB had been added to the TPA, it still activated the tow promoters. However, it seems that 53BP1 may be involved in TPA activation of these promoters because ectopic high expression of 53BP1 significantly reduced the TPA activity. In addition, in the presence of Bisindolylmaleimide-I (BI)- the inhibitor of Protein Kinase C (PKC)- there was no activation for the two promoters, so the PKC is agonized BRCA-1 and ERE activation.

Keywords: BRCA-1, ERE, HTLV-1, TPA

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