Search results for: anti cancer

Authors: Rama Devi Kyatham, D. Ashok, K. S. K. Rao Patnaik, Raju Bathula

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We have shown the importance of pyrazoles as anti-microbial chemical entities. These compounds have generally been considered significant due to their wide range of pharmacological acivities and their discovery motivates new avenues of research.The proposed pyrazoles were synthesized and evaluated for their anti-microbial activities. The Synthesized compounds were analyzed by different spectroscopic methods.

Keywords: pyrazoles, validation, resistant microbial strains, anti-microbial activities

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Authors: Maomao Cao

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Objective: To test the performance of ctDNA methylation for the detection of liver cancer. Methods: A total of 1233 individuals have been recruited in 2017. 15 male and 15 female samples (including 10 cases of liver cancer) were randomly selected in the present study. CfDNA was extracted by MagPure Circulating DNA Maxi Kit. The concentration of cfDNA was obtained by Qubit™ dsDNA HS Assay Kit. A pre-constructed predictive model was used to analyze methylation data and to give a predictive score for each cfDNA sample. Individuals with a predictive score greater than or equal to 80 were classified as having liver cancer. CT tests were considered the gold standard. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for the diagnosis of liver cancer were calculated. Results: 9 patients were diagnosed with liver cancer according to the prediction model (with high sensitivity and threshold of 80 points), with scores of 99.2, 91.9, 96.6, 92.4, 91.3, 92.5, 96.8, 91.1, and 92.2, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of ctDNA methylation for the diagnosis of liver cancer were 0.70, 0.90, 0.78, and 0.86, respectively. Conclusions: ctDNA methylation could be an acceptable diagnostic modality for the detection of liver cancer.

Keywords: liver cancer, ctDNA methylation, detection, diagnostic performance

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Authors: Godfrey Katende, Lillian Nakimera

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The process of caregiving may cause emotional distress in form of anxiety and depression among family carers of cancer patients. Little is known about the prevalence anxiety and depression among family carers of cancer patients in Uganda. This cross-sectional study aimed to determine the prevalence of anxiety and depression among family carers of cancer patients and related factors associated with abnormal levels of anxiety and depression. A total of 119 family carers from Uganda Cancer Institute (UCI) were assessed by the Hospital Anxiety and Depression Scale (HADS) standardized questionnaire. The prevalence of anxiety and depression among family carers was high (45% and 26 % respectively); (2) abnormal levels of anxiety (ALA) and depression (ALD) was significantly associated with being a relative carer. Incorporating evidence based psychological therapies targeting family carers into usual care of cancer patients is imperative.

Keywords: anxiety, cancer, carer, cross-sectional design, depression, Uganda

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Authors: Harukuni Tokuda, Xu FengHao, Nobutaka Suzuki

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As part of an ongoing our projects to investigate the anti-tumor promoring properties (chemopreventive potency) of Gromwell seed, dry powder materials and its active compounds were carried out through useful test systems. Gromwell seed (Coix lachryma-jobi seed) (GS) is a grass crop that has long been used and played a role in traditional medicine as a nourishing food, and for the treatment of various aliments, paticularly cancer. The application of a new screening procedure which utilizes the synergistic effect of short-chain fatty acids and phorbol esters in enable rapid and easy detection of naturally occurring substances(anti-tumor promoters chemo-preventive agents) with inhibition of Epstein-Barr virus(EBV) activation, using human lymphblastoid cells. In addition, we have now extended these investigations to a new tumorigenesis model in which we initiated the tumors with DMBA intiation and promoted with 1.7 nmol of TPA in two-stage mouse skin test and other models. these results provide a basis for further development of these botanical supplements for human cancer chemoprevention and observations seem that this materials more extensively as one of the trials for the purpose of complementary and alternative medicine.

Keywords: chemoprevention, medicinal plant, mouse, carcinogenesis systems

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Authors: Reynaldo Esquivel, Pedro Hernandez, Aaron Martinez-Higareda, Sergio Tena-Cano, Enrique Alvarez-Ramos, Armando Lucero-Acuna

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Stimuli-responsive nanomaterials play an essential role in loading, transporting and well-distribution of anti-cancer compounds in the cellular surroundings. The outstanding properties as the Lower Critical Solution Temperature (LCST), hydrolytic cleavage and protonation/deprotonation cycle, govern the release and delivery mechanisms of payloads. In this contribution, we experimentally determine the load efficiency and release of antineoplastic Vincristine Sulfate into PNIPAM-Interpenetrated-Chitosan (PIntC) nanoparticles. Structural analysis was performed by Fourier Transform Infrared Spectroscopy (FT-IR) and Proton Nuclear Magnetic Resonance (1HNMR). ζ-Potential (ζ) and Hydrodynamic diameter (DH) measurements were monitored by Electrophoretic Mobility (EM) and Dynamic Light scattering (DLS) respectively. Mathematical analysis of the release pharmacokinetics reveals a three-phase model above LCST, while a monophasic of Vincristine release model was observed at 32 °C. Cytotoxic essays reveal a noticeable enhancement of Vincristine effectiveness at low drug concentration on HeLa cervix cancer and MDA-MB-231 breast cancer.

Keywords: nanoparticles, vincristine, drug delivery, PNIPAM

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Authors: Ram Sharma, Esha Chatterjee, Santosh Kumar Guru, Kunal Nepali

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A tractable anti-lung cancer agent was identified via the installation of a Ring C expanded synthetic analogue of the alkaloid vasicinone [7,8,9,10-tetrahydroazepino[2,1-b] quinazolin-12(6H)-one (TAZQ)] as a surface recognition part in the HDAC inhibitory three-component model. Noteworthy to mention that the candidature of TAZQ was deemed suitable for accommodation in HDAC inhibitory pharmacophore as per the results of the fragment recruitment process conducted by our laboratory. TAZQ was pinpointed through the fragment screening program as a synthetically flexible fragment endowed with some moderate cell growth inhibitory activity against the lung cancer cell lines, and it was anticipated that the use of the aforementioned fragment to generate hydroxamic acid functionality (zinc-binding motif) bearing HDAC inhibitors would boost the antitumor efficacy of TAZQ. Consistent with our aim of applying epigenetic targets to the treatment of lung cancer, a strikingly potent anti-lung cancer scaffold (compound 6) was pinpointed through a series of in-vitro experiments. Notably, the compounds manifested a magnificent activity profile against KRAS and EGFR mutant lung cancer cell lines (IC50 = 0.80 - 0.96 µM), and the effects were found to be mediated through preferential HDAC6 inhibition (IC50 = 12.9 nM). In addition to HDAC6 inhibition, the compounds also elicited HDAC1 and HDAC3 inhibitory activity with an IC50 value of 49.9 nM and 68.5 nM, respectively. The HDAC inhibitory ability of compound 6 was also confirmed from the results of the western blot experiment that revealed its potential to decrease the expression levels of HDAC isoforms (HDAC1, HDAC3, and HDAC6). Noteworthy to mention that complete downregulation of the HDAC6 isoform was exerted by compound 6 at 0.5 and 1 µM. Moreover, in another western blot experiment, treatment with hydroxamic acid 6 led to upregulation of H3 acK9 and α-Tubulin acK40 levels, ascertaining its inhibitory activity toward both the class I HDACs and Class II B HDACs. The results of other assays were also encouraging as treatment with compound 6 led to the suppression of the colony formation ability of A549 cells, induction of apoptosis, and increase in autophagic flux. In silico studies led us to rationalize the results of the experimental assay, and some key interactions of compound 6 with the amino acid residues of HDAC isoforms were identified. In light of the impressive activity spectrum of compound 6, a pH-responsive nanocarrier (hyaluronic acid-compound 6 nanoparticles) was prepared. The dialysis bag approach was used for the assessment of the nanoparticles under both normal and acidic circumstances, and the pH-sensitive nature of hyaluronic acid-compound 6 nanoparticles was confirmed. Delightfully, the nanoformulation was devoid of cytotoxicity against the L929 mouse fibroblast cells (normal settings) and exhibited selective cytotoxicity towards the A549 lung cancer cell lines. In a nutshell, compound 6 appears to be a promising adduct, and a detailed investigation of this compound might yield a therapeutic for the treatment of lung cancer.

Keywords: HDAC inhibitors, lung cancer, scaffold, hyaluronic acid, nanoparticles

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Authors: Hector Jose Velazquez-Gonzalez, Norma Maldonado-Santiago, Laura Pietri-Gomez

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Cancer is one of the first cause of death in the world, most of them are women. In Puerto Rico, there is a permanent controversy on the conceptuation of what really involves a disability, also in when a chronic illness, like cancer, should be considered a disability. The aim of the research was to identify functional limitation in 50 women survivors of cancer. In turn, to know the meanings that 6 women attributed to cancer with a focus on functionality. We conducted a mix method research based on surveys and narratives. We administered the World Health Organization Disability Assessment, version 2.0, which obtained a Cronbach’s alpha of .949 on the general scale, and from .773 to .956 on the six domains. The domain that obtained the highest average was social participation (M= 33.89, SD= 20.434), but it was not significant in the disability percentage. Also, there was no significance in the disability percentage in the other five domains. In a matter of meanings, we conduct a semistructured interview to 6 participants. All of them do not refer to cancer as a disability, either they do not know that in Puerto Rico cancer is considered as a disability by the law. However, participants agree that cancer at the time of treatment and subsequent to it, has significant effects on functional limitations (fatigue, pain, cognitive limitations, and weakness, among others. Psychooncologic practice should encourage the constant assessment of the functionality to identify the needs that emerge from oncological diagnosis. So that psychosocial intervention could be considered as critical in cancer treatment to promote a better quality of life and well-being in a person with cancer.

Keywords: cancer, Puerto Rico, disability, psychosocial approach

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Authors: M. A. Ferhat, M. N. Boukhatem, F. Chemat

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Since the available anti-inflammatory drugs exert an extensive variety of side effects, the search for new anti-inflammatory agents has been a priority of pharmaceutical industries. The aim of the present study was to assess the anti-inflammatory activities of the essential oil of rose geranium (RGEO). The chemical composition of the RGEO was investigated by gas chromatography. The major components were citronellol (29.13%), geraniol (12.62%), and citronellyl formate (8.06%). In the carrageenan induced paw edema, five different groups were established and RGEO was administered orally in three different doses. RGEO (100 mg/kg) was able to significantly reduce the paw edema with a comparable effect to that observed with diclofenac, the positive control. In addition, RGEO showed a potent anti-inflammatory activity by topical treatment in the method of croton oil-induced ear edema. When the dose was 5 or 10 ml of RGEO per ear, the inflammation was reduced by 73 and 88%, respectively. This is the first report to demonstrate a significant anti-inflammatory activity of Algerian RGEO. In addition, histological analysis confirmed that RGEO inhibited the inflammatory responses in the skin. Our results indicate that RGEO may have significant potential for the development of novel anti-inflammatory drugs with improved safety profile.

Keywords: anti-inflammatory effect, carrageenan, citronellol, histopathology, Rose geranium

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Authors: Afaf Abdallah, Moawia Elsadig

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Background: Cervical cancer is the second most common women cancer among worldwide; representing 13% of female cancers. In Sudan, it ranks as the second most frequent cancer among women as other developing countries. Aim: Is to study awareness, attitude of nursing students towards cervical cancer prevention. The results: Most of the students were not aware of other screening methods than Pap smear test. However, half of the respondents showed positive attitudes towards HPV vaccination. More than two-thirds of respondents exhibited a positive attitude and were willing to undergo Pap smear in the future. Conclusion: The study shows that the majority of the participants have poor information, education would motivate nurses to participate actively in awareness raising, screening, and management.

Keywords: cervical cancer, knowledge, attitude, screening

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Authors: Bok Yae Chung, Eun Hee Oh

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Breast cancer patients require more nutritional interventions than others. However, a few studies have attempted to assess the overall nutritional status, to reduce body weight and BMI by improving diet, and to improve the prognosis of cancer for breast cancer patients. The purpose of this study was to evaluate the effect of diet intervention in the breast cancer patients through meta-analysis. For the study purpose, 16 studies were selected by using PubMed, ScienceDirect, ProQuest and CINAHL. Meta-analysis was performed using a random-effects model, and the effect size on outcome variables in breast cancer was calculated. The effect size for outcome variables of diet intervention was a large effect size. For heterogeneity, moderator analysis was performed using intervention type and intervention duration. All moderators did not significant difference. Diet intervention has significant positive effects on outcome variables in breast cancer. As a result, it is suggested that the timing of the intervention should be no more than six months, but a strategy for sustaining long-term intervention effects should be added if nutritional intervention is to be administered for breast cancer patients in the future.

Keywords: breast cancer, diet, mete-analysis, intervention

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Authors: Candice Lemaitre

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During the 1990s, an alliance of international intergovernmental and non-governmental organizations proposed a set of regulatory norms designed to reduce corruption. Many governments in developing countries, such as Vietnam, enacted these global anti-corruption norms into their domestic law. This article draws on empirical research to understand why these anti-corruption norms have failed to reduce corruption in Vietnam and many other developing countries. Rather than investigating state compliance with global anti-corruption provisions, a topic that has already attracted considerable attention, this article aims to explore the comparatively under-researched area of business compliance. Based on data collected from semi-structured interviews with business managers in Vietnam and archival research, this article examines how businesses in Vietnam interpret and comply with global anti-corruption norms. It investigates why different types of companies in Vietnam engage with and respond to these norms in different ways. This article suggests that global anti-corruption norms have not been effective in reducing corruption in Vietnam because there is fragmentation in the way companies in Vietnam interpret and respond to these norms. This fragmentation results from differences in the epistemic (or interpretive) communities that companies draw upon to interpret global anti-corruption norms. This article uses discourse analysis to understand how the communities interpret global anti-corruption norms. This investigation aims to generate some predictive insights into how companies are likely to respond to anti-corruption regimes based on global anti-corruption norms.

Keywords: anti-corruption, business law, legal transfer, Vietnam

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

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

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

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Authors: Razieh Zarei, Hassan zm, Abolghasem Ajami, Darush Moslemi, Narges Afsary, Amrollah Mostafa-zade

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Introduction: IL-23 is responsible for the differentiation and expansion of Th17/ThIL-17 cells from naive CD4+ T cells. Therefore, may be IL-23/IL17 axis involve in a variety of allergic and autoimmune diseases, such as RA, MS, inflammatory bowel disease (IBD), and asthma. TGF-β is also share for the differentiation Th17 producing IL-17 and CD4+CD25+Foxp3hiT regulatory cells from naïve CD4+ T cells which are involved in the regulation of immune response, maintaining immunological self-tolerance and immune homeostasis ,and the control of autoimmunity and cancer surveillance. Therefore, T regulatory cells play a key role in autoimmunity, allergy, cancer, infectious disease, and the induction of transplantation tolerance. Vitamin A and it's derivatives (retinoids) inhibit or reverse the carcinogenic process in some types of cancers in oral cavity,head and neck, breast, skin, liver, and blood cells. Shark is a murine organism and its cartilage has antitumor peptides to prevent angiogenesis, in vitro. Our purpose is whether simultaneous oral treatment vitamin A and shark cartilage can modulate IL-23/IL-17 and CD4CD25Foxp3 T regulatory cell/TGF-β pathways and Th1/Th2 immunity in patients with gastric cancer. Materials and Methods: First investigated an imbalanced supernatant of cytokines exist in patients with gastric cancer by ELISA. Associated with cytokines measuring such as IL-23,IL-17,TGF-β,IL-4 and γ-IFN, then flow cytometry was employed to determine whether the peripheral blood mononuclear cells such as CD4+CD25+Foxp3highT regulatory cells in patients with gastric cancer were changed correspondingly. Results: An imbalance between IL-17 secretion and TGF-β/Foxp3 t regulatory cell pathway and so, Th1 immunity (γ-IFN production) and TH2 immunity (IL-4 secretion) was not seen in patients with gastric cancer treated by vitamin A and shark cartilage. But, the simultaneously presented down-regulation of IL-23 indicated, at least cytokine level. Conclusion: Il-23, as a pro-angiogenesis cytokine, probably, help to tumor growth. Hence, suggested that down-regulation of IL-23, at least cytokine level, is useful for anti-tumor immune responses in patients with gastric cancer.

Keywords: IL-23/IL17 axis, TGF-β/CD4CD25Foxp3 T regulatory pathway, γ-IFN, IL-4, shark cartilage and gastric cancer

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Authors: Nilubon Kurubanjerdjit, Nattakarn Iam-On, Ka-Lok Ng

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MicroRNAs are small non-coding RNA found in many different species. They play crucial roles in cancer such as biological processes of apoptosis and proliferation. The identification of microRNA-target genes can be an essential first step towards to reveal the role of microRNA in various cancer types. In this paper, we predict miRNA-target genes for lung cancer by integrating prediction scores from miRanda and PITA algorithms used as a feature vector of miRNA-target interaction. Then, machine-learning algorithms were implemented for making a final prediction. The approach developed in this study should be of value for future studies into understanding the role of miRNAs in molecular mechanisms enabling lung cancer formation.

Keywords: microRNA, miRNAs, lung cancer, machine learning, Naïve Bayes, SVM

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Authors: Spira A., Marabelle A., Kientop D., Moser E., Mumm J.

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Background: Both interleukin-2 (IL-2) and interleukin-10 (IL-10) have been extensively studied for their stimulatory function on T cells and their potential to obtain sustainable tumor control in RCC, melanoma, lung, and pancreatic cancer as monotherapy, as well as combination with PD-1 blockers, radiation, and chemotherapy. While approved, IL-2 retains significant toxicity, preventing its widespread use. The significant efforts undertaken to uncouple IL-2 toxicity from its anti-tumor function have been unsuccessful, and early phase clinical safety observed with PEGylated IL-10 was not met in a blinded Phase 3 trial. Deka Biosciences has engineered a novel molecule coupling wild-type IL-2 to a high affinity variant of Epstein Barr Viral (EBV) IL-10 via a scaffold (scFv) that binds to epidermal growth factor receptors (EGFR). This patented molecule, termed DK210 (EGFR), is retained at high levels within the tumor microenvironment for days after dosing. In addition to overlapping and non-redundant anti-tumor function, IL-10 reduces IL-2 mediated cytokine release syndrome risks and inhibits IL-2 mediated T regulatory cell proliferation. Methods: DK210 (EGFR) is being evaluated in an open-label, dose-escalation (Phase 1) study with 5 (0.025-0.3 mg/kg) monotherapy dose levels and (expansion cohorts) in combination with PD-1 blockers, or radiation or chemotherapy in patients with advanced solid tumors overexpressing EGFR. Key eligibility criteria include 1) confirmed progressive disease on at least one line of systemic treatment, 2) EGFR overexpression or amplification documented in histology reports, 3) at least a 4 week or 5 half-lives window since last treatment, and 4) excluding subjects with long QT syndrome, multiple myeloma, multiple sclerosis, myasthenia gravis or uncontrolled infectious, psychiatric, neurologic, or cancer disease. Plasma and tissue samples will be investigated for pharmacodynamic and predictive biomarkers and genetic signatures associated with IFN-gamma secretion, aiming to select subjects for treatment in Phase 2. Conclusion: Through successful coupling of wild-type IL-2 with a high affinity IL-10 and targeting directly to the tumor microenvironment, DK210 (EGFR) has the potential to harness IL-2 and IL-10’s known anti-cancer promise while reducing immunogenicity and toxicity risks enabling safe concomitant cytokine treatment with other anti-cancer modalities.

Keywords: cytokine, EGFR over expression, interleukine-2, interleukine-10, clinical trial

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Authors: Yung-Feng Yen, Yun-Ju Lai

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Background: Metabolic syndrome (MetS) is reversible; however, the effect of changes in MetS status on the risk of incident cancer has not been extensively studied. We aimed to investigate the effects of changes in MetS status on incident cancer risk. Methods: This prospective, longitudinal study used data from Taiwan’s MJ cohort of 157,915 adults recruited from 2002–2016 who had repeated MetS measurements 5.2 (±3.5) years apart and were followed up for the new onset of cancer over 8.2 (±4.5) years. A new diagnosis of incident cancer in study individuals was confirmed by their pathohistological reports. The participants’ MetS status included MetS-free (n=119,331), MetS-developed (n=14,272), MetS-recovered (n=7,914), and MetS-persistent (n=16,398). We used the Fine-Gray sub-distribution method, with death as the competing risk, to determine the association between MetS changes and the risk of incident cancer. Results: During the follow-up period, 7,486 individuals had new development of cancer. Compared with the MetS-free group, MetS-persistent individuals had a significantly higher risk of incident cancer (adjusted hazard ratio [aHR], 1.10; 95% confidence interval [CI], 1.03-1.18). Considering the effect of dynamic changes in MetS status on the risk of specific cancer types, MetS persistence was significantly associated with a higher risk of incident colon and rectum, kidney, pancreas, uterus, and thyroid cancer. The risk of kidney, uterus, and thyroid cancer in MetS-recovered individuals was higher than in those who remained MetS but lower than MetS-persistent individuals. Conclusions: Persistent MetS is associated with a higher risk of incident cancer, and recovery from MetS may reduce the risk. The findings of our study suggest that it is imperative for individuals with pre-existing MetS to seek treatment for this condition to reduce the cancer risk.

Keywords: metabolic syndrome change, cancer, risk factor, cohort study

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Authors: Yung-Chih Kuo, I-Hsuan Lee

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Solid lipid nanoparticles (SLNs) conjugated with aprotinin (Apr) and melanotransferrin antibody (Anti-MTf) were used to carry doxorubicin (Dox) across the blood–brain barrier (BBB) for glioblastoma multiforme (GBM) chemotherapy. Dox-entrapped SLNs with grafted Apr and Anti-MTf (Apr-Anti-MTf-Dox-SLNs) were applied to a cultured monolayer comprising human brain-microvascular endothelial cells (HBMECs) with regulation of human astrocyte (HAs) and to a proliferated colony of U87MG cells. Based on the average particle diameter, zeta potential, entrapping efficiency of Dox, and grafting efficiency of Apr and Anti-MTf, we found that 40% (w/w) 1,2-dipalmitoyl-sn-glycero-3-phosphocholine in lipids were appropriate for fabricating Apr-Anti-MTf-Dox-SLNs. In addition, Apr-Anti-MTf-Dox-SLNs could prevent Dox from fast dissolution and did not induce a serious cytotoxicity to HBMECs and HAs when compared with free Dox. Moreover, the treatments with Apr-Anti-MTf-Dox-SLNs enhanced the ability of Dox to infuse the BBB and to inhibit the growth of GBM. The current Apr-Anti-MTf-Dox-SLNs can be a promising pharmacotherapeutic preparation to penetrate the BBB for malignant brain tumor treatment.

Keywords: solid lipid nanoparticle, glioblastoma multiforme, blood–brain barrier, doxorubicin

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

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

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

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Authors: Ahmed Khalaf Reyad Raslan

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Cancer stem cells (CSCs) describe a class of pluripotent cancer cells that behave analogously to normal stem cells in their ability to differentiate into the spectrum of cell types observed in tumors. The de-differentiation processes, such as an epithelial-mesenchymal transition (EMT), are known to enhance cellular plasticity. Here, we demonstrate a new hypothesis to use hybrid superparamagnetic magnetite nanoparticles (Fe₃O₄)- graphene oxide functionalized surface with Collagen to target the cancer stem cell as an early detection tool for cancer. We think that with the use of magnetic resonance imaging (MRI) and the new hybrid system would be possible to track the cancer stem cells.

Keywords: hydrogel, alginate, reduced graphene oxide, collagen

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Authors: Rubab Z. Kahlon, Ibtisam Butt, Isma Younis, Aamer G. Mufti

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Worldwide lung cancer 1.61 million cases were seen in both genders. Lung carcinoma is the major cause of both morbidity and mortality in the world. Purpose of the present study was to describe the spatio- temporal trends of lung cancer in both genders. A retrospective study was conducted. Total 1498 patients of lung carcinoma were examined. Only lung cancer patients from all over the Punjab were included in the present study. MS Excel 2010 was used for data tabulation and calculation while the Arc GIS version 9.3 was used for geographical representation of the data. 1498 cases of Lung cancer were found from 2008-2012. The number of male patients was 1236 and female was 262. Majority of the patients were from Lahore districts with 807 patients. Lung cancer was more prevalent in male as compared to female in our region. Increase in the prevalence of lung cancer was prominently seen in the most populated and industrial areas of the Punjab province. Time trend of five years showed fluctuation in the lung cancer incidence during the study period.

Keywords: districts, gender, lung cancer trends, Punjab province of Pakistan

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Authors: Wissem Abdaoui, Nizar M. Mhaidat, Ilhem Mokhtari, Adel Gouri

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Colorectal cancer (CRC) is one of the most common tumors all over the world. Obesity, considered a risk factor of CRC, is characterized by a high level of secreted cytokines from adipose tissue. Among these inflammatory molecules, leptin is considered the key mediator for CRC cancer development and progression by activation of mitogenic and anti apoptotic signaling pathways. Gene expression can be significantly modulated by alterations in DNA methylation patterns. The aim of this study is to investigate the impact of leptin gene methylation on CRC prognosis and sensitivity to chemotherapy. The study involved 70 CRC tissue samples collected from King Abdullah University Hospital (KAUH) from which only 53 was analyzed because of bisulfate fragmentation and low yield of DNA extracted from FFPE tissues. A total of 22 blood samples were collected from healthy volunteers and enrolled as a control group. Leptin promoter methylation was analyzed by methylation specific PCR after bisulfate conversion. Results revealed that the incidence of leptin gene methylation was significantly higher in CRC patients in comparison to that of controls (P < 0.05). The correlation between patient’s demographics and leptin gene methylation was not significant (P < 0.05). However, a significant correlation between leptin gene methylation status and early cancer stages (I, II and III) was found in male but not in female (p < 0.05). Moreover, a significant correlation was found between leptin promoter methylation and early tumor localization T1-2 (p < 0.05). The correlation between epigenetic regulation of leptin and chemosensitivity was not significant. Taken together, these results suggest the possibility to use leptin gene methylation as a biomarker for the evaluation of CRC prognosis and metastasis.

Keywords: colorectal cancer, obesity, leptin, DNA methylation, disease prognosis, bisulfate conversion, chemoresistance

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Authors: Mary Kiviiri Nakawuka, Mary Namugalu, Andrew Otiti

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BACKGROUND Cervical cancer is the fourth most common cancer in women and seventh overall among all cancers worldwide. It accounts for about 7.5% of all female-cancer deaths with 85% occurring in low and middle-income countries and the first most common female cancer in women aged 15 to 44 years in Uganda with an annual number of new cases at 3,915 and 2,275 annual number of cervical cancer deaths in 2012 (ICO INFORMATION CENTRE ON HPV AND CANCER, 2017).Despite the available free cervical cancer screening services whose uptake has been documented to improve the chances of successful treatment of pre-cancers and cancers among women of reproductive age, there is a low uptake of these services thus we sought to examine the uptake of cervical cancer services and associated factors among women of reproductive age (25-49) attending the ART clinic of KISWA HCII in Kampala, Uganda METHODS The research was carried out in the ART clinic of KISWA HCII among 385 participants. An analytical, cross-sectional study with quantitative methods of data collection was used. The study adopted a non-probability convenience sampling method to select participants. Quantitative data was collected through structured questionnaires. RESULTS 72.2% of the participants were found to have been screened for cervical cancer. 36 % of the screened women had a positive HPV or VIA result ,59.2% of the screened women had a negative HPV or VIA result and 4.8% had an invalid HPV test result. Only 39.5% of the participants had adequate overall knowledge about cervical cancer, more than a third of the participants (50%) had moderate or low knowledge and minority of them (10.5%) had no knowledge. There was no significant association between the uptake of cervical cancer screening services among participants and their socio-demographic characteristics. CONCLUSIONS Although majority of the women surveyed had been screened for cervical cancer, a comparatively large number of participants had inadequate knowledge about cervical cancer and therefore there is still need to continue teaching about cervical cancer and this may include education campaigns, improvements to the accessibility and convenience of the screening services.

Keywords: cervical cancer uptake, cervical cancer screening, women of reproductive age., cervical cancer knowledge

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Authors: S. Tebibel, C. Mechati, S. Messaoudi

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Algeria is currently experiencing the same rate of cancer progression as that registered these last years in the western countries. Colorectal cancer, constituting increasingly a major public health problem, is the most common form of cancer after breast and Neck-womb cancer at the woman and prostate cancer at the man. Our work is based on a retrospective study to determine the cases of colorectal cancer through eastern Algeria. Our goal is to carry out an epidemiological, histological and immune- histochemical study to investigate different techniques for the diagnosis of colorectal cancer and their interests and specific in detecting the disease. The study includes 110 patients (aged between 20 to 87 years) with colorectal cancer where the inclusions and exclusions criteria were established. In our study, colorectal cancer, expresses a male predominance, with a sex ratio of 1, 99 and the most affected age group is between 50 and 59 years. We noted that the colon cancer rate is higher than rectal cancer rate, whose frequencies are respectively 60,91 % and 39,09 %. In the series of colon cancer, the ADK lieberkunien is histological the most represented type, or 85,07 % of all cases. In contrast, the proportion of ADK mucinous (colloid mucous) is only 1,49% only. Well-differentiated ADKS, are very significant in our series, they represent 83,58 % of cases. Adenocarcinoma moderately and poorly differentiated, whose proportions are respectively 2,99 % and 0.05 %. For histological varieties of rectal ADK, we see in our workforce that ADK lieberkunien represent the most common histological form, or 76,74%, while the mucosal colloid is 13,95 %. Research of the mutation on the gene encoding K-ras, a major step in the targeted therapy of colorectal cancers, is underway in our study. Colorectal cancer is the subject of much promising research concern: the evaluation of new therapies (antiangiogenic monoclonal antibodies), the search for predictors of sensitivity to chemotherapy and new prognostic markers using techniques of molecular biology and proteomics.

Keywords: adenocarcinoma, age, colorectal cancer, epidemiology, histological section, sex

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Authors: Ji Hye Im, Nguyen T. T. Phuong, Keon Wook Kang

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Estrogens are important for the development and growth of estrogen receptor (ER)-positive breast cancer, for which anti-estrogen therapy is one of the most effective treatments. However, its efficacy can be limited by either de novo or acquired resistance. Aromatase is a key enzyme for the biosynthesis of estrogens, and inhibition of this enzyme leads to profound hypoestrogenism. Here, we found that the basal expression and activity of aromatase were significantly increased in tamoxifen (TAM)-resistant human breast cancer (TAMR-MCF-7) cells compared to control MCF-7 cells. We further revealed that aromatase immunoreactivity in tumor tissues was increased in recurrence group after TAM therapy compared to non-recurrence group after TAM therapy. Phosphorylation of Akt, extracellular signal-regulated kinase (ERK), and p38 kinase were all increased in TAMR-MCF-7 cells. Inhibition of phosphoinositide 3-kinase (PI3K) suppressed the transactivation of the aromatase gene and its enzyme activity. Furthermore, we have also shown that PI3K/Akt-dependent cAMP-response element binding protein (CREB) activation was required for the enhanced expression of aromatase in TAMR-MCF-7 cells. Our findings suggest that aromatase expression is up-regulated in TAM-resistant breast cancer via PI3K/Akt-dependent CREB activation.

Keywords: TAMR-MCF-7, CREB, estrogen receptor, aromatase

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Authors: Arslan Masood Pirzada, Muhammad Naeem, Hafiz Haider Ali, Muhammad Latif, Aown Sammar Raza, Asad Hussain Bukhari, Muhammad Saqib, Muhammad Ijaz

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Cyperus rotundus (Cyperaceae), a medicinal herb, is being traditionally used as a home remedy for the treatment of various clinical conditions like diarrhea, diabetic, pyretic, inflammation, malaria, and for treating stomach and bowel disorders. Its current status is one of the most widespread, troublesome, and economically damaging agronomic weeds, growing wildly in various tropical and sub-tropical regions of the world. Tuber and rhizomes of Cyperus rotundus possess a higher concentration of active ingredients in the form of essential oils, phenolic acids, ascorbic acids and flavonoids, responsible for its remedial properties. Exploitation of any medicinal plant application depends on the crucial and comprehensive information about the therapeutic potential of a plant. Researchers have evaluated and characterized the significance of Cyperus rotundus as an anti-androgenic, anti-bacterial, anti-cancerous, anti-convulsant, anti-diabetic, anti-diarrheal, anti-genotoxic, anti-inflammatory, anti-lipidemic, anti-malarial, anti-mutagenic, anti-obesity, anti-oxidant, anti-uropathogenic, hepato-, cardio-, neuroprotective, and nootropic agent. This paper comprises a broad review to summarize the current state of knowledge about chemical constituents, potential economic uses and therapeutic aspects of Cyperus rotundus that will aid in the development of bioethanol and modern herbal medicine through latest technologies that will promote the ability of this plant in the cure of many clinical disorders.

Keywords: purple nutsedge, chemical composition, economic uses, therapeutic values, future directions

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

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

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

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Authors: Aiza G. Clanor, Lotlot B. Hernandez, Jonna Marie T. Ibuna

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This study aimed to know the coping mechanisms of Batangueño families facing cancer, specifically, those from Cancer Warriors Foundation, Inc. Batangas chapter. The researchers used purposive sampling. This study was limited to the responses provided by the Batangueño families of the cancer patients. A family member of the immediate family with a child facing cancer represents the family as a whole. A total number of forty six (46) respondents were given the questionnaires. Upon analysis, most of the respondents came from rural areas and nuclear family and have Php 5000 and below family monthly income. Most of them have their own houses, and 3 to 5 members, one of whom is a cancer patient diagnosed for more than 2 years. The two most frequently utilized coping strategies were mobilizing the family to acquire and accept help, and reframing. Passive appraisal is the least utilized one. There was a significant difference on the coping mechanisms of the family relative to passive appraisal based on the length of time since the illness was first diagnosed. Based from the study, the researchers developed modules with discussions and activities on cancer awareness, ideas on coping and how to deal with the cancer patients that may help the respondents and other Batangueño families overcome the difficulties in facing cancer. The researchers recommend the modules for they are found to be effective ways to help the families relieve stress, reduce anxiety and improve quality of life.

Keywords: coping with chronic illness, family, psychology, cancer

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Authors: Siti Aisya Gany, Swee Ching Tan, Sook Yee Gan

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Diminished antioxidant defense or increased production of reactive oxygen species in the biological system can result in oxidative stress which may lead to various neurodegenerative diseases including Alzheimer’s disease (AD). Microglial activation also contributes to the progression of AD by producing several pro-inflammatory cytokines, nitric oxide (NO), and prostaglandin E2 (PGE2). Oxidative stress and inflammation have been reported to be possible pathophysiological mechanisms underlying AD. In addition, the cholinergic hypothesis postulates that memory impairment in patient with AD is also associated with the deficit of cholinergic function in the brain. Although a number of drugs have been approved for the treatment of AD, most of these synthetic drugs have diverse side effects and yield relatively modest benefits. Marine algae have great potential in pharmaceutical and biomedical applications as they are valuable sources of bioactive properties such as anti-coagulation, anti-microbial, anti-oxidative, anti-cancer and anti-inflammatory. Hence, this study aimed to provide an overview of the properties of Malaysian seaweeds (Padina australis, Sargassum polycystum and Caulerpa racemosa) in inhibiting oxidative stress, neuroinflammation and cholinesterase enzymes. All tested samples significantly exhibit potent DPPH and moderate Superoxide anion radical scavenging ability (P<0.05). Hexane and methanol extracts of S. polycystum exhibited the most potent radical scavenging ability with IC50 values of 0.1572 ± 0.004 mg/ml and 0.8493 ± 0.02 for DPPH and ABTS assays, respectively. Hexane extract of C. racemosa gave the strongest superoxide radical inhibitory effect (IC50 of 0.3862± 0.01 mg/ml). Most seaweed extracts significantly inhibited the production of cytokine (IL-6, IL-1 β, TNFα) and NO in a concentration-dependent manner without causing significant cytotoxicity to the lipopolysaccharide (LPS)-stimulated microglia cells (P<0.05). All extracts suppressed cytokine and NO level by more than 80% at the concentration of 0.4mg/ml. In addition, C. racemosa and S. polycystum also showed anti-acetylcholinesterase activities with the IC50 values ranging from 0.086-0.115 mg/ml. Moreover, C. racemosa and P. australis were also found to be active against butyrylcholinesterase with IC50 values ranging from 0.118-0.287 mg/ml.

Keywords: anti-cholinesterase, anti-oxidative, neuroinflammation, seaweeds

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Authors: Adebisi Adunola Demehin, Wanlaya Thamnarak, Jaruwan Chatwichien, Chatchakorn Eurtivong, Kiattawee Choowongkomon, Somsak Ruchirawat, Nopporn Thasana

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The epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein involved in cellular signalling processes and, its aberrant activity is crucial in the development of many cancers such as lung cancer. Selaginellaceae are fern allies that have long been used in Chinese traditional medicine to treat various cancer types, especially lung cancer. Biflavonoids, the major secondary metabolites in Selaginellaceae, have numerous pharmacological activities, including anti-cancer and anti-inflammatory. For instance, amentoflavone induces a cytotoxic effect in the human NSCLC cell line via the inhibition of PARP-1. However, to the best of our knowledge, there are no studies on biflavonoids as EGFR inhibitors. Thus, this study aims to investigate the EGFR inhibitory activities of biflavonoids isolated from Selaginella siamensis and Selaginella bryopteris. Amentoflavone, tetrahydroamentoflavone, sciadopitysin, robustaflavone, robustaflavone-4-methylether, delicaflavone, and chrysocauloflavone were isolated from the ethyl-acetate extract of the whole plants. The structures were determined using NMR spectroscopy and mass spectrometry. In vitro study was conducted to evaluate their cytotoxicity against A549, HEPG2, and T47D human cancer cell lines using the MTT assay. In addition, a target-based assay was performed to investigate their EGFR inhibitory activity using the kinase inhibition assay. Finally, a molecular docking study was conducted to predict the binding modes of the compounds. Robustaflavone-4-methylether and delicaflavone showed the best cytotoxic activity on all the cell lines with IC50 (µM) values of 18.9 ± 2.1 and 22.7 ± 3.3 on A549, respectively. Of these biflavonoids, delicaflavone showed the most potent EGFR inhibitory activity with an 84% relative inhibition at 0.02 nM using erlotinib as a positive control. Robustaflavone-4-methylether showed a 78% inhibition at 0.15 nM. The docking scores obtained from the molecular docking study correlated with the kinase inhibition assay. Robustaflavone-4-methylether and delicaflavone had a docking score of 72.0 and 86.5, respectively. The inhibitory activity of delicaflavone seemed to be linked with the C2”=C3” and 3-O-4”’ linkage pattern. Thus, this study suggests that the structural features of these compounds could serve as a basis for developing new EGFR-TK inhibitors.

Keywords: anticancer, biflavonoids, EGFR, molecular docking, Selaginellaceae

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Authors: Jamboor K. Vishwanatha

Abstract:

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

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

Procedia PDF Downloads 321