Search results for: lung cancer cells

Authors: Ibrahim M. Labouta, Marwa H. El-Wakil, Hayam M. Ashour, Ahmed M. Hassan, Manal N. Saudi

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The receptor tyrosine kinase c-Met is an attractive target for therapeutic treatment of cancers nowadays. Among the wide variety of heterocycles that have been explored for developing c-Met kinase inhibitors, the 1,2,4-triazines have been rarely investigated, although they are well known in the literature to possess antitumor activities. Herein we describe the design and synthesis of a novel series of 1,2,4-triazine derivatives possessing N-acylarylhydrazone moiety and another series combining the 1,2,4-triazine scaffold to the well-known anticancer drug 6-MP in order to explore their “double-drug” effect. The synthesized compounds were evaluated for their in vitro antitumor activity against three c-Met addicted cancer cell lines (A549, HT-29 and MKN-45). Most compounds showed moderate to excellent antiproliferative activity and four compounds showed potent inhibitory activity more than the reference drug Foretinib against one or more cancer cell lines. The obtained results revealed that the potent compounds are highly selective to A549 (lung adenocarcinoma) cancer cell line. The c-Met kinase inhibitory activity of the potent derivatives is still under investigation. The present study clearly demonstrates that the 1,2,4-triazine core ring exhibits promising antitumor activity with potential c-Met kinase inhibitory activity.

Keywords: 1, 2, 4-triazine, antitumor, c-Met inhibitor, double-drug

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Authors: Retno Supriyanti, Teguh Budiono, Yogi Ramadhani, Haris B. Widodo, Arwita Mulyawati

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Cervical cancer is the leading cause of mortality in cancer-related diseases. In this diagnosis doctors usually perform several tests to determine the presence of cervical cancer in a patient. However, these checks require support equipment to get the results in more detail. One is by using ultrasonography. However, for the developing countries most of the existing ultrasonography has a low resolution. The goal of this research is to obtain abnormalities on low-resolution ultrasound images especially for cervical cancer case. In this paper, we emphasize our work to use Image Enhancement for pre-processing image quality improvement. The result shows that pre-processing stage is promising to support further analysis.

Keywords: cervical cancer, mortality, low-resolution, image enhancement.

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Authors: Jose R. Garcia, Lexi Frankel, Amalia Ardeljan, Sergio Medina, Ali Yasback, Omar Rashid

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Background: Helicobacter pylori (H. pylori) is a gram-negative, spiral-shaped bacterium that affects nearly half of the population worldwide and humans serve as the principal reservoir. Infection rates usually follow an inverse relationship with hygiene practices and are higher in developing countries than developed countries. Incidence varies significantly by geographic area, race, ethnicity, age, and socioeconomic status. H. pylori is primarily associated with conditions of the gastrointestinal tract such as atrophic gastritis and duodenal peptic ulcers. Infection is also associated with an increased risk of carcinogenesis as there is evidence to show that H. pylori infection may lead to gastric adenocarcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma. It is suggested that H. pylori infection may be considered as a systemic condition, leading to various novel associations with several different neoplasms such as colorectal cancer, pancreatic cancer, and lung cancer, although further research is needed. Emerging evidence suggests that H. pylori infection may offer protective effects against Mycobacterium tuberculosis as a result of non-specific induction of interferon- γ (IFN- γ). Similar methods of enhanced immunity may affect the development of bronchogenic carcinoma due to the antiproliferative, pro-apoptotic and cytostatic functions of IFN- γ. The purpose of this study was to evaluate the correlation between Helicobacter pylori infection and the incidence of bronchogenic carcinoma. Methods: The data was provided by a Health Insurance Portability and Accountability Act (HIPAA) compliant national database to evaluate the patients infected versus patients not infected with H. pylori using ICD-10 and ICD-9 codes. Access to the database was granted by the Holy Cross Health, Fort Lauderdale for the purpose of academic research. Standard statistical methods were used. Results:-Between January 2010 and December 2019, the query was analyzed and resulted in 163,224 in both the infected and control group, respectively. The two groups were matched by age range and CCI score. The incidence of bronchogenic carcinoma was 1.853% with 3,024 patients in the H. pylori group compared to 4.785% with 7,810 patients in the control group. The difference was statistically significant (p < 2.22x10-16) with an odds ratio of 0.367 (0.353 - 0.383) with a confidence interval of 95%. The two groups were matched by treatment and incidence of cancer, which resulted in a total of 101,739 patients analyzed after this match. The incidence of bronchogenic carcinoma was 1.929% with 1,962 patients in the H. pylori and treatment group compared to 4.618% with 4,698 patients in the control group with treatment. The difference was statistically significant (p < 2.22x10-16) with an odds ratio of 0.403 (0.383 - 0.425) with a confidence interval of 95%.

Keywords: bronchogenic carcinoma, helicobacter pylori, lung cancer, pathogen-associated molecular patterns

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Authors: Mohamed Bakry Mohamed Ali, Mohamed Ehab El-Din Mustafa, Joseph Naiem Sabet Aziz, Sarah Mahmoud Ali Kaooh

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Background: Acute lung injury (ALI) is one of the major challenges in intensive care medicine. The most common extrapulmonary cause of ALI is sepsis, accounting more than 30% of the cases in humans. Lipopolysaccharide (LPS) has gained wide acceptance as a clinically relevant model of ALI. Lipopolysaccharide is a glycoprotein forming the major constituent of bacterial endotoxin. Losartan is angiotensin II type 1 (AT1) receptor antagonists. It is widely used for management of hypertension. It was recently suggested that losartan protects against septic ALI. It would thereby prevent LPS-induced ALI. Aim of the work and design of the experiment: This work investigated the injurious effect of lipopolysaccharide (LPS) and ALI on adult male albino rat at 24 hours and 14 days of LPS administration and the possible protective role of losartan pretreatment. LPS has deteriorated animal survival and behavior. It increased lung weight and induced lung histological damage. These changes could be much reduced by the losartan pretreatment. Conclusion: Administration of losartan before LPS could largely reduce these LPS/ ALI induced short and long term alterations. It could be recommended that patients susceptible to developing ALI, as in ICU, should receive a protective dose of angitensin II type 1 (AT1) receptor blocker as losartan.

Keywords: acute lung injury (ALI), lipopolysaccharide (LPS), losartan

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Authors: Elif Erdem, Nalan Kaya, Gonca Ozan, Durrin Ozlem Dabak, Enver Ozan

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This study was carried out to determine the histological and biochemical changes in the lungs of the rat pups exposed to tobacco smoke during pregnancy period and to investigate the protective effects of alpha lipoic acid, which is administered during pregnancy, on these changes. In our study, 24 six-week old Spraque-Dawley female rats weighing 160 ± 10 g were used (n:7). Rats were randomly divided into four equal groups: group I (control), group II (tobacco smoke), group III (tobacco smoke + alpha lipoic acid) and group IV (alpha lipoic acid). Rats in the group II, group III were exposed to tobacco smoke twice a day for one hour starting from eight weeks before mating and during pregnancy. In addition to tobacco smoke, 20 mg/kg of alpha lipoic acid was administered via oral gavage to the rats in the group III. Only alpha lipoic acid was administered to the rats in the group IV. Once after the delivery, all administrations were stopped. On the 7 and 21th days, the seven pups of all groups were decapitated. A portion of the lung was taken and stained with HE, PAS and Masson. In addition to immunohistochemical staining of surfactant protein A, vascular endothelial growth factor, caspase-3, TUNEL method was also used to determine apoptosis. Biochemical analyzes were performed with some part of the lung tissue specimens. In the histological evaluations performed under light microscopy, inflammatory cell increase, hemorrhagic areas, edema, interalveolar septal thickening, alveolar numbers decrease, degeneration of some bronchi and bronchial epithelium, epithelial cells that were fallen into the lumen and hyaline membrane formation were observed in tobacco smoke group. These findings were ameliorated in tobacco smoke + ALA group. Hyaline membrane formation was not detected in this group. The TUNEL positive cell numbers a significant increase was detected in the tobacco smoke group, whereas a significant decrease was detected in the tobacco smoke + ALA group. In terms of the immunoreactivity of both SP-A and VEGF, a significant decrease was observed in the tobacco smoke group, and a significant increase was observed in the tobacco smoke + ALA group. Regarding the immunoreactivity of caspase-3, there was a significant increase in the group of tobacco smoke and a significant decrease in the group of tobacco smoke + ALA. The malondialdehyde levels were determined to be significantly increased in the tobacco smoke group, and a significant decreased in the tobacco smoke + ALA. Glutathione and superoxide dismutase enzyme activities showed a significant decrease in the group of tobacco smoke and a significant increase in the tobacco smoke + ALA group. In conclusion, we suggest that the exposure to tobacco smoke during pregnancy leads to morphological, histopathological and functional changes on lung development by causing oxidative damage in lung tissues of neonatal rats and the maternal use of alpha lipoic acid can provide a protective effect on the neonatal lung development against this oxidative stress originating from tobacco smoke.

Keywords: alpha lipoic acid, lung, neonate, tobacco smoke, pregnancy

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Authors: Salina Yahya Saddik

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The present study is designed to demonstrate the Ovarian Surface Epithelial cells (OSE) Estrogen Receptor α (ERα) and Progesterone Receptor (PR) during pregnancy and estrous cycle in rat. Moreover, determination of the levels of plasma progesterone, estradiol, FSH and LH were also made. The levels of plasma progesterone, estradiol, FSH and LH concentrations were determined on days 7 (n=5), 14 (n=5), and 21(n=5) of pregnancy in three groups of rats and during the estrous cycle (n=5) using ELISA kit. Immunohistochemical method for PR and ERα expression was also made on the ovary. During pregnancy, FSH and LH remained low except at term when LH levels began to increase from 16 ng/ml to 47 ng/ml. Progesterone levels significantly exceeded estradiol values in all pregnant rats with a peak value of 202 ng/ml on day 14. Elevated progesterone levels were associated negatively with LH and estradiol levels during pregnancy. The levels of estradiol surged significantly on day 21. Immunohistochemistry of the ovary showed low levels of OSE cells staining positive for ERα expression. ERα positive cells were absent on day 7 and 14 of pregnancy, only day 21 recorded a very low percentage of immunostaining (0.5%) within the nuclei of OSE cells. On the contrary, immunostaining of PR was not observed within the nuclei of OSE cells in all groups of study. In conclusions, these results may suggest that progesterone effect during pregnancy seems to be overriding the positive effect of estrogens on OSE cells. High progesterone levels may have a direct negative effect on gonadotropin production and thereby it might inhibit events leading to both follicular development and OSE proliferation. Understanding the factors affecting OSE proliferation may help elucidating the mechanism(s) of assisted diseases such as ovarian cancer.

Keywords: ovarian surface, pregnancy, gonadotropins, steroids

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Authors: Chaliya Wamaloon, Malee Chaisaena, Nusara Prasertsri

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Informal caregivers providing home-based palliative and end-of-life (EOL) care to people with advanced cancer is needed, however, there has not been develop caregiver skills for the EOL in cancer patients. The aim of this research was to study the model development of caregiver skills for the EOL in cancer patients. Mixed methods research was conducted in 3 phases. All subjects were in Ubon Rathchathani Cancer Hospital including 30 EOL cancer patient caregivers, 30 EOL cancer patients, and 111 health care professionals who provided care for the EOL cancer patients and 30 EOL target participants who had been trained to be cancer patient caregivers. The research tools were questionnaires, semi structured interviews, and caregiver skills questionnaires. Data were analyzed by using percentage, mean, standard deviation, pair t-test, and content analysis. The result from this study showed the model development of caregiver skills for cancer patients consisted of 9 domains skills: 1. monitoring, 2. interpreting, 3. making decisions, 4. taking action, 5. making adjustments, 6. providing hands-on care, 7. accessing resources, 8. working together with the ill patients, and 9. navigating the healthcare system. The model composed of skills development curriculum for cancer patient caregivers, Manual of palliative care for caregivers, diary of health care records for cancer patients, and the evaluation model of development of caregiver skills for EOL cancer patients. The results of the evaluation in the development model of caregiver skills for EOL cancer patients showed that the caregivers were satisfied with the model of development for caregiver skills at a high level. The comparison of the caregiver skills before and after obtaining the development of caregivers skills revealed that it improved at a statistically significant level (p < 0.05).

Keywords: caregiver, caregiver skills, cancer patients, end of life

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Authors: Kai-Cheng Hsu, Tzu-Ying Sung, Jinn-Moon Yang

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Colorectal cancer (CRC) is one of the main causes of cancer death in the world. Although several drugs have been developed to treat colorectal cancer, such as Regorafenib and 5-FU, their efficacy is often limited by the development of drug resistance. Therefore, development of new drugs with new scaffolds is necessary to treat CRC. Here, we used site-moiety maps to identify inhibitors against PIM1, LIMK1, SRC, and mTOR, which are often overexpressed in CRC. A site-moiety map represents physicochemical properties and moiety preferences of a binding site through anchors. An anchor contains three elements: (1) conserved interacting residues of a binding pocket; (2) moiety preference of the binding pocket; and (3) the type (e.g., hydrogen-bonding or van der Waals interactions) of interaction between the moieties and the binding pocket. Then, we performed a structure-based virtual screening of ~260,000 compounds and selected compound candidates with high site-moiety map scores for bioassays. Among these candidates, compound 1 and compound 2 inhibited the growth of CRC cells with IC50 values of <10 μM. The experimental result of enzyme-based assays indicated that compound 1 is a dual inhibitor against PIM1 (IC50 6 μM) and LIMK1(IC50 11 μM). Compound 2 was predicted as a SRC inhibitor and will be further validated. The compounds inhibited different protein targets compared to the current drugs. We believe that the compounds provide a starting point to design new drugs for CRC treatment.

Keywords: colorectal cancer, drug discovery, site-moiety map, virtual screening, PIM1, LIMK1

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Authors: Rafia S. Al-lamki, Jun Wang, Simon Pacey, Jordan Pober, John R. Bradley

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Tumor necrosis factor alpha (TNF), signaling through TNFR2, may act an autocrine growth factor for renal tubular epithelial cells. Clear cell renal carcinomas (ccRCC) contain cancer stem cells (CSCs) that give rise to progeny which form the bulk of the tumor. CSCs are rarely in cell cycle and, as non-proliferating cells, resist most chemotherapeutic agents. Thus, recurrence after chemotherapy may result from the survival of CSCs. Therapeutic targeting of both CSCs and the more differentiated bulk tumor populations may provide a more effective strategy for treatment of RCC. In this study, we hypothesized that TNFR2 signaling will induce CSCs in ccRCC to enter cell cycle so that treatment with ligands that engage TNFR2 will render CSCs susceptible to chemotherapy. To test this hypothesis, we have utilized wild-type TNF (wtTNF) or specific muteins selective for TNFR1 (R1TNF) or TNFR2 (R2TNF) to treat either short-term organ cultures of ccRCC and adjacent normal kidney (NK) tissue or cultures of CD133+ cells isolated from ccRCC and adjacent NK, hereafter referred to as stem cell-like cells (SCLCs). The effect of cyclophosphamide (CP), currently an effective anticancer agent, was tested on CD133+SCLCs from ccRCC and NK before and after R2TNF treatment. Responses to TNF were assessed by flow cytometry (FACS), immunofluorescence, and quantitative real-time PCR, TUNEL, and cell viability assays. Cytotoxic effect of CP was analyzed by Annexin V and propidium iodide staining with FACS. In addition, we assessed the effect of TNF on isolated SCLCs differentiation using a three-dimensional (3D) culture system. Clinical samples of ccRCC contain a greater number SCLCs compared to NK and the number of SCSC increases with higher tumor grade. Isolated SCLCs show expression of stemness markers (oct4, Nanog, Sox2, Lin28) but not differentiation markers (cytokeratin, CD31, CD45, and EpCAM). In ccRCC organ cultures, wtTNF and R2TNF increase CD133 and TNFR2 expression and promote cell cycle entry whereas wtTNF and R1TNF increase TNFR1 expression and promote cell death of SCLCs. Similar findings are observed in SCLCs isolated from NK but the effect was greater in SCLCs isolated from ccRCC. Application of CP distinctly triggered apoptotic and necrotic cell death in SLCSs pre-treatment with R2TNF as compared to CP treatment alone, with SCLCs from ccRCC more sensitive to CP compared to SLCS from NK. Furthermore, TNF promotes differentiation of SCLCs to an epithelial phenotype in 3D cultures, confirmed by cytokeratin expression and loss of stemness markers Nanog and Sox2. The differentiated cells show positive expression of TNF and TNFR2. These findings provide evidence that selective engagement of TNFR2 drive CSCs to cell proliferation/differentiation, and targeting of cycling cells with TNFR2 agonist in combination with anti-cancer agents may be a potential therapy for RCC.

Keywords: cancer stem cells, ccRCC, cell cycle, cell death, TNF, TNFR1, TNFR2, CD133

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Authors: Farrah Putri Salmanida, Mei-Li Wu, Rika Wahyuningtyas, Wen-Bin Chung, Hso-Chi Chaung, Ko-Tung Chang

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Within the field of immunotherapy, oncolytic virotherapy (OVT) employs dual approaches that directly eliminate tumor cells while preserving healthy ones and indirectly reprogram the tumor microenvironment (TME) to elicit antitumor responses. Within the TME, tumor associated macrophages (TAMs) manifest characteristics akin to those of anti-inflammatory M2 macrophages, thus earning the designation of M2-like TAMs. In prior research, two antigens denoted as A1 (g6Ld10T) and A3 (ORF6L5), derived from a complete sequence of ORF5 with partial sequence of ORF6 in Porcine Reproductive and Respiratory Syndrome Virus Genotype 2 (PRRSV-2), demonstrated the capacity to repolarize M2-type porcine alveolar macrophages (PAMs) into M1 phenotypes. In this study, we sought for utilizing OVT strategies by introducing A1 or A3 on TAMs to endow them with the anti-tumor traits of M1 macrophages while retaining their capacity to target cancer cells. Upon exposing human THP-1-derived M2 macrophages to a cross-species test with 2 µg/ml of either A1 or A3 for 24 hours, real time PCR revealed that A3, but not A1, treated cells exhibited upregulated gene expressions of M1 markers (CCR7, IL-1ß, CCL2, Cox2, CD80). These cells reacted to virus-derived antigen, as evidenced by increased expression of pattern-recognition receptors TLR3, TLR7, and TLR9, subsequently providing feedback in the form of type I interferon responses like IFNAR1, IFN-ß, IRF3, IRF7, OAS1, Mx1, and ISG15. Through an MTT assay, only after 15 µg/ml of A3 treatment could the cell viability decrease, with a predicted IC50 of 16.96 µg/ml. Interestingly, A3 caused dose-dependent toxicity to a rat C6 glial cancer cell line even at doses as low as 2.5 µg/ml and reached its IC50 at 9.419 µg/ml. Using Annexin V/7AAD staining and PCR test, we deduced that a significant proportion of C6 cells were undergoing the early apoptosis phase predominantly through the intrinsic apoptosis cascade involving Bcl-2 family proteins. Following this stage, we conducted a test on A3’s repolarization ability, which revealed a significant rise in M1 gene expression markers, such as TNF, CD80, and IL-1ß, in M2-like TAMs generated in vitro from murine RAW264.7 macrophages grown with conditioned medium of 4T1 breast cancer cells. This was corroborated by the results of transcriptome analysis, which revealed that the primary subset among the top 10 to top 30 significantly upregulated differentially expressed genes (DEGs) dominantly consisted of M1 macrophages profiles, including Ccl3, Ccl4, Csf3, TNF, Bcl6b, Stc1, and Dusp2. Our findings unveiled the remarkable potential of the PRRSV-derived antigen A3 to repolarize macrophages while also being capable of selectively inducing apoptosis in cancerous cells. While further in vivo study is needed for A3, it holds promise as an adjuvant by its dual effects in cancer therapy modalities.

Keywords: cancer cell apoptosis, interferon responses, macrophage repolarization, recombinant protein

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Authors: Ping-Lun Jiang, Hung-Jun Lin, Shen-Fu Lin, Mei-Yin Chien, Ting-Wei Li, Chun-Han Lin, Der-Zen Liu

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Mucosal vaccine induces both mucosal (secretory IgA) and systemic immune responses and it is considered an ideal vaccination strategy for prevention of infectious diseases. One important point to be considered in mucosal vaccination is effective antigen delivery system which can manage effective delivery of antigen to antigen-presenting cells (APCs) of mucosal. In the present study, cationic gelatin nanoparticles were prepared as ideal carriers for more efficient antigen delivery. The average diameter of cationic gelatin nanoparticle was approximate 190 nm, and the zeta potential was about +45 mV, then ovalbumin (OVA) was physically absorbed onto cationic gelatin nanoparticle. The OVA absorption rate was near 95% the zeta potential was about +20 mV. We show that cationic gelatin nanoparticle effectively facilitated antigen uptake by mice bone marrow-derived dendritic cells (mBMDCs) and RAW264.7 cells and induced higher levels of pro-inflammatory cytokines. C57BL/6 mice twice immunized intranasally with OVA-absorbed cationic gelatin nanoparticle induced high levels of OVA-specific IgG in the serum and IgA in their in the nasal and lung wash fluid. These results indicate that nasal administration of cationic gelatin nanoparticles induced both mucosal and systemic immune responses and cationic gelatin nanoparticles might be a potential antigen delivery carrier for further clinical applications.

Keywords: antigen delivery, antigen-presenting cells, gelatin nanoparticle, mucosal vaccine

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Authors: V. R. Ahire, A. Kumar, B. N. Pandey, K. P. Mishra, G. R. Kulkarni

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Radiation therapy is an effective vital strategy used globally in the treatment of cervical cancer. However, radiation efficacy principally depends on the radiosensitivity of the tumor, and not all patient exhibit significant response to irradiation. A radiosensitive tumor is easier to cure than a radioresistant tumor which later advances to local recurrence and metastasis. Herbal polyphenols are gaining attention for exhibiting radiosensitization through various signaling. Current work focuses to study the radiosensitization effect of ellagic acid (EA), on HeLa cells. EA intermediated radiosensitization of HeLa cells was due to the induction γ-H2AX foci formation, G1 phase cell cycle arrest, and loss of reproductive potential, growth inhibition, drop in the mitochondrial membrane potential and protein expression studies that eventually induced apoptosis. Irradiation of HeLa in presence of EA (10 μM) to doses of 2 and 4 Gy γ-radiation produced marked tumor cytotoxicity. EA also demonstrated radio-protective effect on normal cell, NIH3T3 and aided recovery from the radiation damage. Our results advocate EA to be an effective adjuvant for improving cancer radiotherapy as it displays striking tumor cytotoxicity and reduced normal cell damage instigated by irradiation.

Keywords: apoptotic radiosensitivity, ellagic acid, mitochondrial potential, cell-cycle arrest

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Authors: Nalan Kaya, Gonca Ozan, Elif Erdem, Neriman Colakoglu, Enver Ozan

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The toxic effects of tobacco smoke exposure have been detected in numerous studies. Ellagic acid (EA), (2,3,7,8-tetrahydroxy [1]-benzopyranol [5,4,3-cde] benzopyran 5,10-dione), a natural phenolic lactone compound, is found in various plant species including pomegranate, grape, strawberries, blackberries and raspberries. Similar to the other effective antioxidants, EA can safely interact with the free radicals and reduces oxidative stress through the phenolic ring and hydroxyl components in its structure. The aim of the present study was to examine the protective effects of ellagic acid against oxidative damage on lung tissues of rats induced by tobacco smoke. Twenty-four male adult (8 weeks old) Spraque-Dawley rats were divided randomly into 4 equal groups: group I (Control), group II (Tobacco smoke), group III (Tobacco smoke + corn oil) and group IV (Tobacco smoke + ellagic acid). The rats in group II, III and IV, were exposed to tobacco smoke 1 hour twice a day for 12 weeks. In addition to tobacco smoke exposure, 12 mg/kg ellagic acid (dissolved in corn oil), was applied to the rats in group IV by oral gavage. Equal amount of corn oil used in solving ellagic acid was applied to the rats by oral gavage in group III. At the end of the experimental period, rats were decapitated. Lung tissues and blood samples were taken. The lung slides were stained by H&E and Masson’s Trichrome methods. Also, galactin-3 stain was applied. Biochemical analyzes were performed. Vascular congestion and inflammatory cell infiltration in pulmonary interstitium, thickness in interalveolar septum, cytoplasmic vacuolation in some macrophages and galactin-3 positive cells were observed in histological examination of tobacco smoke group. In addition to these findings, hemorrhage in pulmonary interstitium and bronchial lumen was detected in tobacco smoke + corn oil group. Reduced vascular congestion and hemorrhage in pulmoner interstitium and rarely thickness in interalveolar septum were shown in tobacco smoke + EA group. Compared to group-I, group-II GSH level was decreased and MDA level was increased significantly. Nevertheless group-IV GSH level was higher and MDA level was lower than group-II. The results indicate that ellagic acid could protect the lung tissue from the tobacco smoke harmful effects.

Keywords: ellagic acid, lung, rat, tobacco smoke

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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: 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: Van Tran Thi Thuy, Cheol Won Lim, Dukjoon Kim

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A series of biodegradable copolymers based on polyaspartamide (PASPAM) were synthesized by grafting hydrophilic O-(2-aminoethyl)-O'-methylpoly(ethylene glycol) (MPEG), hydrophobic cholic acid (CA), and pH-sensitive hydrazine (Hyd) segments on a PASPAM backbone. The hydrazine group was effectively cleaved to release doxorubicin (DOX) conjugated on PASPAM in an acidic environment. The chemical structure of the polymer and the degree of substitution of each graft segment were analyzed using FT-IR and 1H-NMR spectroscopy. The size of the MPEG/Hyd/CA-g-PASPAM copolymer self-aggregates was examined by dynamic light scattering (DLS) and transmission electron microscope (TEM). The mean diameter of the self - aggregates increased from 125 to 200 nm at pH 7.4, as the degree of substitution of CA increased from 10 to 20 %. The release kinetics of DOX was strongly affected by the pH of the releasing medium. While less than 30% of the DOX-loaded was released in about 30 h at pH 7.4, more than 60% was released at pH 5.0 within the same time. The viability tests of human breast cancer cells (MCF-7) and human embryonic kidney cells (293T) show the potential application of MPEG/Hyd/CA-g-PASPAM copolymer self-aggregates in the controlled intracellular delivery for cancer treatments.

Keywords: pH-sensitive, drug delivery, polyaspartamide, self-assembly, nano-aggregates

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Authors: Aysegul Alyamac, Sukru Gulec

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Ankaferd Blood Stopper (ABS) is a plant extract used to stop bleeding caused by injuries and surgical interventions. ABS also involved in wound healing of intestinal mucosal damage due to oxidative stress and inflammation. Inflammatory Bowel Disease (IBD) is a common chronic disorder of the gastrointestinal tract that causes abdominal pain, diarrhea, and gastrointestinal bleeding, and increases the risk of colon cancer. Inflammation is an essential factor in the development of IBD. The various studies have been performed about the physiological effects of ABS; however, ABS dependent mechanism on colonic inflammation has not been elucidated. Thus, the protective effect of ABS on colonic inflammation was investigated in this study. The Caco-2 and RAW 264.7 murine macrophage cells were used as a model of in vitro colonic inflammation. RAW 264.7 cells were treated with lipopolysaccharide (LPS) for 12 hours to induce the inflammation, and a conditional medium was obtained. Caco-2 cells were treated with 15 µl/ml ABS for 4 hours, then incubated with conditional medium and the cells also were incubated with 15 µl/ml ABS and conditional medium together for 4 hours. Tumor necrosis factor alpha (TNF-α) protein levels were targeted in testing inflammatory condition and its level was significantly increased (25 fold, p<0.001) compared to the control group by using Enzyme-Linked Immunosorbent Assay (ELISA) method. The COX-2 mRNA level was used as a marker gene to show the possible anti-inflammatory effect of ABS in Caco-2 cells. RAW cells-derived conditional medium significantly (3.3 fold, p<0.001) induced cyclooxygenase-2 (COX-2) mRNA levels in Caco-2 cells. The pretreatment of Caco-2 cells caused a significant decrease (3.3 fold, p<0.001) in COX-2 mRNA levels relative to conditional medium given group. Furthermore, COX-2 mRNA level was significantly reduced (4,7 fold, p<0.001) in ABS and conditional medium treated group. These results suggest that ABS might have an anti-inflammatory effect in vitro.

Keywords: Ankaferd blood stopper, CaCo-2, colonic inflammation, RAW 264.7

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Authors: Ranjot Kaur, Om P. Katare, Anupama Sharma, Sarah R. Dennison, Kamalinder K. Singh, Bhupinder Singh

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Respiratory microbial infections being among the top leading cause of death worldwide are difficult to treat as the microbes reside deep inside the airways, where only a small fraction of drug can access after traditional oral or parenteral routes. As a result, high doses of drugs are required to maintain drug levels above minimum inhibitory concentrations (MIC) at the infection site, unfortunately leading to severe systemic side-effects. Therefore, delivering antimicrobials directly to the respiratory tract provides an attractive way out in such situations. In this context, current study embarks on the systematic development of lung lia pid-modified chitosan nanoparticles for inhalation of voriconazole. Following the principles of quality by design, the chitosan nanoparticles were prepared by ionic gelation method and further coated with major lung lipid by precipitation method. The factor screening studies were performed by fractional factorial design, followed by optimization of the nanoparticles by Box-Behnken Design. The optimized formulation has a particle size range of 170-180nm, PDI 0.3-0.4, zeta potential 14-17, entrapment efficiency 45-50% and drug loading of 3-5%. The presence of a lipid coating was confirmed by FESEM, FTIR, and X-RD. Furthermore, the nanoparticles were found to be safe upto 40µg/ml on A549 and Calu-3 cell lines. The quantitative and qualitative uptake studies also revealed the uptake of nanoparticles in lung epithelial cells. Moreover, the data from Spraytec and next-generation impactor studies confirmed the deposition of nanoparticles in lower airways. Also, the interaction of nanoparticles with DPPC monolayers signifies its biocompatibility with lungs. Overall, the study describes the methodology and potential of lipid-coated chitosan nanoparticles in futuristic inhalation nanomedicine for the management of pulmonary aspergillosis.

Keywords: dipalmitoylphosphatidylcholine, nebulization, DPPC monolayers, quality-by-design

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Authors: Michaela Chovancova, Pavel Niedoba

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For the treatment of acute and chronic lung diseases it is preferred to deliver medicaments by inhalation. The drug is delivered directly to tracheobronchial tree. This way allows the given medicament to get directly into the place of action and it makes rapid onset of action and maximum efficiency. The transport of aerosol particles in the particular part of the lung is influenced by their size, anatomy of the lungs, breathing pattern and airway resistance. This article deals with calculation of airway resistance in the lung model of Horsfield. It solves the problem of determination of the pressure losses in bifurcation and thus defines the pressure drop at a given location in the bronchial tree. The obtained data will be used as boundary conditions for transport of aerosol particles in a central part of bronchial tree realized by Computational Fluid Dynamics (CFD) approach. The results obtained from CFD simulation will allow us to provide information on the required particle size and optimal inhalation technique for particle transport into particular part of the lung.

Keywords: human lungs, bronchial tree, pressure losses, airways resistance, flow, breathing

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Authors: Mahsa Falahatpour

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Introduction: This study aims to explore how inter-observer variability in manual tumor segmentation impacts the reliability of radiomic features in non–small cell lung cancer (NSCLC). Methods: The study included twenty-three NSCLC tumors. Each patient had three tumor segmentations (VOL1, VOL2, VOL3) contoured on PET/CT scans by three radiation oncologists. Dice coefficients (DCS) were used to measure the segmentation variability. Radiomic features were extracted with 3D-slicer software, consisting of 66 features: first-order (n=15), second-order (GLCM, GLDM, GLRLM, and GLSZM) (n=33). The inter-observer variability of radiomic features was assessed using the intraclass correlation coefficient (ICC). An ICC > 0.8 indicates good stability. Results: The mean DSC of VOL1, VOL2, and VOL3 was 0.80 ± 0.04, 0.85 ± 0.03, and 0.76 ± 0.06, respectively. 92% of all extracted radiomic features were found to be stable (ICC > 0.8). The GLCM texture features had the highest stability (96%), followed by GLRLM features (90%) and GLSZM features (87%). The DSC was found to be highly correlated with the stability of radiomic features. Conclusion: The variability in inter-observer segmentation significantly impacts radiomics analysis, leading to a reduction in the number of appropriate radiomic features.

Keywords: PET/CT, radiomics, radiotherapy, segmentation, NSCLC

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Authors: Ibtissem El Ouar, Cornelia Braicu, Dalila Naimi, Alexendru Irimie, Ioana Berindan-Neagoe

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Helix aspersa, 'the garden snail' is a big land snail widely found in the Mediterranean countries, it is one of the most consumed species in the west of Algeria. It is commonly used in zootherapy to purify blood and to treat cardiovascular diseases and liver problems. The aim of our study is to investigate, the antitumor activity of an aqueous extract from Helix aspersa prepared by the traditional method on Hs578T; a triple negative breast cancer cell line. Firstly, the free radical scavenging activity of H. aspersa extract was assessed by measuring its capability for scavenging the radical 2,2-diphenyl-1-picrylhydrazyl (DPPH), as well as its ability to reduce ferric ion by the FRAP assay (ferric reducing ability). The cytotoxic effect of H. aspersa extract against Hs578T cells was evaluated by the MTT test (3-(4,5- dimethylthiazl-2-yl)-2,5- diphenyltetrazolium bromide)) while the mode of cell death induced by the extract has been determined by fluorescence microscopy using acredine orange/ethidium bromide (AO/EB) probe. The level of TNFα has also measured in cell medium by ELISA method. The results suggest that H. aspersa extract has an antioxidant activity, especially at high concentrations, it can reduce DPPH radical and ferric ion. The MTT test shows that H. aspersa extract has a great cytotoxic effect against breast cancer cells, the IC50 value correspond of the dilution 1% of the crude extract. Moreover, the AO/EB staining shows that TNFα induced necrosis is the main form of cell death induced by the extract. In conclusion, the present study may open new perspectives in the search for new natural anticancer drugs.

Keywords: breast cancer, Helix aspersa, Hs578t cell line, necrosis

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Authors: Agatha Bebbington, Terry Tetley, Kathryn Hadler

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Background: Astronauts will set foot on the Moon later this decade, and are at high risk of lunar dust inhalation. Freshly-fractured lunar dust produces reactive oxygen species in solution, which are known to cause cellular damage and inflammation. Cytotoxicity and inflammatory mediator release was measured in pulmonary alveolar epithelial cells (cells that line the gas-exchange zone of the lung) exposed to a lunar dust simulant, LMS-1. It was hypothesised that freshly-fractured LMS-1 would result in increased cytotoxicity and inflammatory mediator release, owing to the angular morphology and high reactivity of fractured particles. Methods: A human alveolar epithelial type 1-like cell line (TT1) and a human macrophage-like cell line (THP-1) were exposed to 0-200μg/ml of unground, aged-ground, and freshly-ground LMS-1 (screened at <22μm). Cell viability, cytotoxicity, and inflammatory mediator release (IL-6, IL-8) were assessed using MMT, LDH, and ELISA assays, respectively. LMS-1 particles were characterised for their size, surface area, and morphology before and after grinding. Results: Exposure to LMS-1 particles did not result in overt cytotoxicity in either TT1 epithelial cells or THP-1 macrophage-like cells. A dose-dependent increase in IL-8 release was observed in TT1 cells, whereas THP-1 cell exposure, even at low particle concentrations, resulted in increased IL-8 release. Both cytotoxic and pro-inflammatory responses were most marked and significantly greater in TT1 and THP-1 cells exposed to freshly-fractured LMS-1. Discussion: LMS-1 is a novel lunar dust simulant; this is the first study to determine its toxicological effects on respiratory cells in vitro. An increased inflammatory response in TT1 and THP-1 cells exposed to ground LMS-1 suggests that low particle size, increased surface area, and angularity likely contribute to toxicity. Conclusions: Evenlow levels of exposure to LMS-1 could result in alveolar inflammation. This may have pathological consequences for astronauts exposed to lunar dust on future long-duration missions. Future research should test the effect of low-dose, intermittent lunar dust exposure on the respiratory system.

Keywords: lunar dust, LMS-1, lunar dust simulant, long-duration space travel, lunar dust toxicity

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Authors: Angely Sim Jia Wun, Sasa Arsovski

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Numerous studies have been conducted on the segmentation of medical images. Segmenting the lungs is one of the common research topics in those studies. Our research stemmed from the lack of solutions for automatic bone, airway, and vessel segmentation, despite the existence of multiple lung segmentation techniques. Consequently, currently, available software tools used for medical image segmentation do not provide automatic lung, bone, airway, and vessel segmentation. This paper presents segmentation techniques along with an interactive software tool architecture for segmenting bone, lung, airway, and vessel tissues. Additionally, we propose a method for creating binary masks from automatically generated segments. The key contribution of our approach is the technique for automatic image thresholding using adjustable Hounsfield values and binary mask extraction. Generated binary masks can be successfully used as a training dataset for deep-learning solutions in medical image segmentation. In this paper, we also examine the current software tools used for medical image segmentation, discuss our approach, and identify its advantages.

Keywords: lung segmentation, binary masks, U-Net, medical software tools

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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: Haile F. Darge, Hsieh C. Tsai

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The tumor microenvironment affects the therapeutic outcomes of cancer disease. In a malignant tumor, overexpression of vascular endothelial growth factor (VEGF) provokes the production of pathologic vascular networks. This results in a hostile tumor environment that hinders anti-cancer drug activities and profoundly fuels tumor progression. In this study, we develop a strategy of sequential sustain release of the anti-angiogenic drug: Bevacizumab(BVZ), and anti-cancer drug: Doxorubicin(DOX) which had a synergistic effect on cancer treatment. Poly (D, L-Lactide)- Poly (ethylene glycol) –Poly (D, L-Lactide) (PDLLA-PEG-PDLLA) thermo-sensitive hydrogel was used as a vehicle for local delivery of drugs in a single platform. The in vitro release profiles of the drugs were investigated and confirmed a relatively rapid release of BVZ (73.56 ± 1.39%) followed by Dox (61.21 ± 0.62%) for a prolonged period. The cytotoxicity test revealed that the copolymer exhibited negligible cytotoxicity up to 2.5 mg ml-1 concentration on HaCaT and HeLa cells. The in vivo study on Hela xenograft nude mice verified that hydrogel co-loaded with BVZ and DOX displayed the highest tumor suppression efficacy for up to 36 days with pronounce anti-angiogenic effect of BVZ and with no noticeable damage on vital organs. Therefore, localized co-delivery of anti-angiogenic drug and anti-cancer drugs by the hydrogel system may be a promising approach for enhanced chemotherapeutic efficacy in cancer treatment.

Keywords: anti-angiogenesis, chemotherapy, controlled release, thermo-sensitive hydrogel

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Authors: R. Stalin, D. Karthick, H. Haseena Banu, T. P. Sachidanandam, P. Shanthi

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Background: Breast cancer is emerging as one of the leading cause of cancer related deaths and hence there arises the need to look out for drugs which are more targets specific with minimal side effects. In recent times, there is a shift towards alternative medicine due to low cost and less side effects. Siddha system of medicine is one the oldest system of medicine practiced against various ailments. Tridham (TD) is a herbal formulation prepared in our laboratory consisting of Terminalia chebula, Elaeocarpus ganitrus and Prosopis cineraria in a definite ratio (TD) and its anticancer potential is evaluated in terms of induction of apoptosis. Objective: The present study was designed to investigate the anti proliferative effect of TD and 1,2,3,4,6-penta-O-galloyl-b-D-glucose (PGG), a pure compound isolated from TD on human mammary carcinoma cell line (MCF-7). Materials and Methods: Cell viability was studied using MTT analysis and trypan blue staining. Mitochondrial membrane potential was studied using DAPI staining. The protein and mRNA expressions of pro-apoptotic and anti- apoptotic markers namely Bax, Bad, Bcl-2 and caspases were also assessed by Western Blotting and RT PCR. Results: Viability studies of TD and PGG treated MCF-7 cells showed an inhibition in cell growth in time and dose dependent manner. The alteration in mitochondrial membrane potential was restored through treatment with TD and PGG which was confirmed by DAPI staining. The protein and mRNA expression of pro-apoptotic markers was found to be significantly increased in TD and PGG treated cells with a concomitant decrease in anti-apoptotic markers. Conclusion: The results of the study suggest that TD and PGG exhibit their anticancer effect through its membrane stabilizing property and activation of apoptotic cascade in MCF-7 cells.

Keywords: apoptosis, mammary carcinoma, MCF-7, penta galloyl glucose, Tridham

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Authors: Mohammad Kazem Mohammadi

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The use of anticancer agents forms an important part of the treatment of cancer of various types. Uranyl Complexes with DPHMP ligand have been used for the prevention and treatment of cancers. U(IV) metal complexes prepared by reaction of uranyl salt UO2 (NO3)2.6H2O with DPHMP in dry acetonitrile. Characterization of the ligand and its complexes was made by microanalyses, FT-IR, 1H NMR, 13C NMR and UV–Visible spectroscopy. These new complex showed excellent antitumor activity against two kinds of cancer cells that that are HT29:Haman colon adenocarcinoma cell line and T47D:human breast adenocarcinoma cell line.

Keywords: uranyl complexes, DPHMP ligand, antitumor activity, HT29, T47D

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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: Yong Zhang

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Light has proven to be useful in a wide range of biomedical applications such as fluorescence imaging, photoacoustic imaging, optogenetics, photodynamic therapy, photothermal therapy, and light controlled drug/gene delivery. Taking photodynamic therapy (PDT) as an example, PDT has been proven clinically effective in early lung cancer, bladder cancer, head, and neck cancer and is the primary treatment for skin cancer as well. However, clinical use of PDT is severely constrained by the low penetration depth of visible light through thick tissue, limiting its use to target regions only a few millimeters deep. One way to enhance the range is to use invisible near-infrared (NIR) light within the optical window (700–1100nm) for biological tissues, extending the depth up to 1cm with no observable damage to the intervening tissue. We have demonstrated use of NIR-to-visible upconversion fluorescent nanoparticles (UCNPs), emitting visible fluorescence when excited by a NIR light at 980nm, as a nanotransducer for PDT to convert deep tissue-penetrating NIR light to visible light suitable for activating photosensitizers. The unique optical properties of UCNPs enable the upconversion wavelength to be tuned and matched to the activation absorption wavelength of the photosensitizer. At depths beyond 1cm, however, tissue remains inaccessible to light even within the NIR window, and this critical depth limitation renders existing phototherapy ineffective against most deep-seated cancers. We have demonstrated some new treatment modalities for deep-seated cancers based on UCNP hydrogel implants and miniaturized, wirelessly powered optoelectronic devices for light delivery to deep tissues.

Keywords: upconversion, fluorescent, nanoparticle, bioimaging, photodynamic therapy

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