Search results for: Difficult intubation in glottic cancer

Authors: Ya-Ching Fu, An-Kuo Chou, Boon-Fatt Tan, Chi-Nien Chen, Wen-Chien Yang, Pou-Leng Cheong

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Blind oro-/naso-pharyngeal suction and feeding tube placement are very common practices in neonatal intensive care unit. Though esophageal perforation is a rare complication of these instrumentations, its prevalence is highest in extremely premature neonates. Due to its association with significant morbidity (including respiratory deterioration, pneumothorax, and sepsis) and even mortality, it is an important issue to prevent this iatrogenic complication in the field of premature care. We demonstrate an esophageal perforation in an extreme-low-birth-weight neonate after oro-gastric tube placement. This female baby weighing 680 grams was delivered by caesarean section at 25 weeks of gestational age. She initially received oro-tracheal intubation with mechanical ventilation which was smoothly weaned to non-invasive positive-pressure ventilation at 7-day-old. However, after insertion of a 5-French oro-gastric tube, the baby’s condition suddenly worsened with apnea requiring mechanical ventilation. Her chest radiogram showed the oro-gastric tube in right pleural space, and thus another oro-gastric tube was replaced, and its position was radiographically confirmed. The malpositioned tube was then removed. The baby received 2-week course of intravenous antibiotics for her esophageal perforation. Feeding was then reintroduced and increased to full feeds in a smooth course. She was discharged at 107-day-old. Esophageal perforation in newborn is very rare. Sudden respiratory deterioration in a neonate after naso-/oro-gastric tube placement should alarm us to consider esophageal perforation, and further radiological investigation is required for the diagnosis. Tube materials, patient condition, and age are major risk factors of esophageal perforation. The use of softer tube material, such as silicone, in extreme premature baby might prevent this fetal complication.

Keywords: esophageal perforation, preterm, newborn, feeding tube

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Authors: AliAkbar Hafezi, Jamshid Abedi, Jalal Taherian, Behnam Kadkhodaei, Mahsa Elahi

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Background. Peripheral neuropathy is a common side effect of the administration of neurotoxic chemotherapy agents. This adverse effect is a major dose-limiting factor of many commonly used chemotherapy drugs. Currently, there are no Food and Drug Administration (FDA) approved medications for the prevention or treatment of chemotherapy-induced peripheral neuropathy. Therefore, this study was performed to investigate the efficacy and safety of metformin on paclitaxel-induced peripheral neuropathy (PIPN). Methods. In this randomized clinical trial, cancer patients who were candidates for chemotherapy with paclitaxel referred to the radiation oncology departments in Iran from 2022 to 2023 were studied. Patients were randomly divided into two groups; 1- Case group (n = 30) received metformin 500 mg orally twice a day after meals during chemotherapy with paclitaxel, and 2- Control group (30 people) received chemotherapy without metformin or any additional medication. Patients were visited in terms of numbness or other neurological symptoms two weeks before chemotherapy, 1-2 days before and weekly during chemotherapy, and at the end of the study. They were assessed by nerve conduction study (NCS) before intervention and one week after the end of chemotherapy. The primary outcome was the efficacy in reducing PIPN and the secondary outcome was adverse effects. Eventually, the outcomes were compared between the two groups of patients. Results. A total of 60 female cancer patients receiving chemotherapy with paclitaxel were evaluated in two groups. The groups were matched in terms of age, body mass index, fasting blood sugar, smoking, pathologic stage, and creatinine levels. The results showed that 18 patients (60.0 %) in the case group and 23 patients (76.6 %) in the control group had PIPN clinically (P = 0.267), and NCS showed 11 patients (36.6 %) in the case group and 15 patients (50.0 %) in the control group suffered from PIPN which no significant difference was observed between the two groups (P = 0.435). Diarrhea (n = 3; 10.0 %) and nausea (n = 3; 10.0 %) were the most common side effects of metformin in the case group and no serious side effects (lactic acidosis and anemia) were found in these patients. Conclusion. This study indicated that metformin did not significantly prevent PIPN in cancer patients receiving chemotherapy, although the frequency of peripheral neuropathy in the case group was lower than in the control group. The use of metformin in the patients had acceptable safety and no serious side effects were reported.

Keywords: peripheral neuropathy, chemotherapy, paclitaxel, metformin

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Authors: Ayubova Nargiza Mirzabixulaevna, Kiryakov Dmitriy Andreyevich

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Relevance: According to experts from the World Health Organization, in 80% of cases, the causes of skin cancer are external factors: polluted air, radioactive substances, solar flares, and free radicals. In dermatology, one of the most common related to obligate diseases is actinic keratosis. Actinic keratosis (AC) is an area of abnormal proliferation and differentiation of keratinocytes, which carry the risk of progression into invasive squamous cell carcinoma of the skin. The purpose of the study is to study the prevalence of various forms of actinic keratosis among the population of Uzbekistan. Materials and methods of research: The study is based on the observation and clinical laboratory examination of 96 patients who were divided by gender and age. Women made up 45% and men made up 55%. The youngest patient was 43 years old, and the oldest was 92 years old. The control group consisted of 40 patients. The following clinical signs were evaluated: peeling, hyperkeratosis, erythema, pigmentation, atrophy. Results: Studies have shown that of all forms of actinic keratosis, erythematous (36%), hyperkeratotic (27%), pigmented (12%), cutaneous horn (7.0%), atrophic (7.0%), Actinic cheilitis (6%), lichenoid (5%) are common. Conclusion: Thus, the data we have obtained indicate that the main and pronounced clinical sign in the erythematous form is erythema and the hyperkeratic form is often found. With cutaneous horn, there is a sharp hyperkeratosis of the epidermis.

Keywords: actinic keratosis, patient, skin cancer, obligate diseases

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Authors: Tripti Mishra, Shipra Shukla, Sanjeev Meena, , Ruchi Singh, Mahesh Pal, D. K. Upreti, Dipak Datta

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Roccella montagnei belongs to lichen family Roccelleceae growing luxuriantly along the coastal regions of India. As Roccella has been shown to be bioactive, we prepared methanolic extract and assessed its anticancer potential. The methanolic extract showed significant in vitro cytotoxic activity against four human cancer cell lines such as Colon (DLD-1, SW-620), Breast (MCF-7), Head and Neck (FaDu). This prompted us to isolate bioactive compounds through column chromatography. Two compounds Roccellic acid and Everninic acid have been isolated, out of which Everninic acid is reported for the first time. Both the compounds have been tested for in vitro cytotoxic activity in which Roccellic acid showed strong anticancer activity as compared to the Everninic acid. CDK-10 (Cyclin-dependent kinase) contributes to proliferation of cancer cells, and aberrant activity of these kinases has been reported in a wide variety of human cancers. These kinases, therefore, constitute biomarkers of proliferation and attractive pharmacological targets for the development of anticancer therapeutics. Therefore both the isolated compounds were tested for in silico molecular docking study against CDK-10 isomer enzyme to support the cytotoxic activity.

Keywords: cytotoxic activity, everninic acid, roccellic acid, R. montagnei

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Authors: Elyas Palantei, Dewiani, Farid Armin, Ardiansyah

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High precision of printed microwave sensor utilized for sensing and monitoring the potential breast cancer existed in women breast tissue was optimally computed. The single element of UWB printed sensor that successfully modeled through several numerical optimizations was multiple fabricated and incorporated with woman bra to form the spherical sensors array. One sample of UWB microwave sensor obtained through the numerical computation and optimization was chosen to be fabricated. In overall, the spherical sensors array consists of twelve stair patch structures, and each element was individually measured to characterize its electrical properties, especially the return loss parameter. The comparison of S11 profiles of all UWB sensor elements is discussed. The constructed UWB sensor is well verified using HFSS programming, CST programming, and experimental measurement. Numerically, both HFSS and CST confirmed the potential operation bandwidth of UWB sensor is more or less 4.5 GHz. However, the measured bandwidth provided is about 1.2 GHz due to the technical difficulties existed during the manufacturing step. The configuration of UWB microwave sensing and monitoring system implemented consists of 12 element UWB printed sensors, vector network analyzer (VNA) to perform as the transceiver and signal processing part, the PC Desktop/Laptop acting as the image processing and displaying unit. In practice, all the reflected power collected from whole surface of artificial breast model are grouped into several numbers of pixel color classes positioned on the corresponding row and column (pixel number). The total number of power pixels applied in 2D-imaging process was specified to 100 pixels (or the power distribution pixels dimension 10x10). This was determined by considering the total area of breast phantom of average Asian women breast size and synchronizing with the single UWB sensor physical dimension. The interesting microwave imaging results were plotted and together with some technical problems arisen on developing the breast sensing and monitoring system are examined in the paper.

Keywords: UWB sensor, UWB microwave imaging, spherical array, breast cancer monitoring, 2D-medical imaging

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Authors: Nkechi V. Enwuru, Bullum Nkeki, Elizabeth A. Adekoya, Olumide A. Adebesin, Rebecca F. Peters, Victoria A. Aikhomu, Mendie E. U.

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Background: Probiotics are live microbial feed supplement beneficial for host. Probiotics and their postbiotic products have been used to prevent or treat various health conditions. However, the products cell viability is often low due to harsh conditions subjected during processing, handling, storage, and gastrointestinal transit. These strongly influence probiotics’ benefits; thus, viability is essential for probiotics to produce health benefits for the host. Microencapsulation is a promising technique with considerable effects on probiotic survival. The study is aimed to formulate a microencapsulated probiotic and evaluate its viability, antimicrobial efficacy, and cytotoxic activity of its postbiotic on the MCF-7 breast cancer cell line. Method: Human and animal raw milk were sampled for lactic acid bacteria. The isolated bacteria were identified using conventional and VITEK 2 systems. The identified lactic acid bacterium was encapsulated using spray-dried and extrusion methods. The free, encapsulated, and chitosan-coated encapsulated probiotics were tested for viability in simulated-gastric intestinal (SGI) fluid and different storage conditions at refrigerated (4oC) and room (25oC) temperatures. The disintegration time and weight uniformity of the spray-dried hard gelatin capsules were tested. The antimicrobial property of free and encapsulated probiotics was tested against enteric pathogenic isolates from antiretroviral therapy (ART) treated HIV-positive patients. The postbiotic of the free cells was extracted, and its cytotoxic effect on the MCF-7 breast cancer cell line was tested through an MTT assay. Result: The Lactobacillus plantarum was isolated from animal raw milk. Zero-size hard gelatin L. plantarum capsules with granules within a size range of 0.71–1.00 mm diameter was formulated. The disintegration time ranges from 2.14±0.045 to 2.91±0.293 minutes, while the average weight is 502.1mg. Simulated gastric solution significantly affected viability of both free and microcapsules. However, the encapsulated cells were more protected and viable due to impermeability in the microcapsules. Furthermore, the viability of free cells stored at 4oC and 25oC were less than 4 log CFU/g and 6 log CFU/g respectively after 12 weeks. However, the microcapsules stored at 4oC achieved the highest viability among the free and microcapsules stored at 25oC and the free cells stored at 4oC. Encapsulated cells were released in the simulated gastric fluid, viable and effective against the enteric pathogens tested. However, chitosan-coated calcium alginate encapsulated probiotics significantly inhibited Shigella flexneri, Candida albicans, and Escherichia coli. The Postbiotic Metabolites (PM) of L. plantarum produced a cytotoxic effect on the MCF-7 breast cancer cell line. The postbiotic showed significant cytotoxic activity similar to 5FU, a standard antineoplastic agent. The inhibition concentration of 50% growth (IC50) of postbiotic metabolite K3 is low and consistent with the IC50 of the positive control (Cisplatin). Conclusions: Lactobacillus plantarum postbiotic exhibited a cytotoxic effect on the MCF-7 breast cancer cell line and could be used as combined adjuvant therapy in breast cancer management. The microencapsulation technique protects the probiotics, improving their viability and delivery to the gastrointestinal tract. Chitosan enhances antibacterial efficacy; thus, chitosan-coated microencapsulated L. plantarum probiotics could be more effective and used as a combined therapy in HIV management of opportunistic enteric infection.

Keywords: probiotics, encapsulation, gastrointestinal conditions, antimicrobial effect, postbiotic, cytotoxicity effect

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Authors: Sayed Maeen Badshah, Kuen-Song Lin, Abrar Hussain, Jamshid Hussain

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Liver cancer is a significant global health issue, ranking fifth in incidence and second in mortality. Effective therapeutic strategies are urgently needed to combat this disease, particularly in regions with high prevalence. This study focuses on developing and characterizing fluorescent organometallic frameworks as distinct drug delivery carriers with potential applications in both the treatment and biological imaging of liver cancer. This work introduces two distinct organometallic frameworks: the cake-shaped GQD@NH₂-MIL-125 and the cross-shaped M8U6/FM8U6. The GQD@NH₂-MIL-125 framework is particularly noteworthy for its high fluorescence, making it an effective tool for biological imaging. X-ray diffraction (XRD) analysis revealed specific diffraction peaks at 6.81ᵒ (011), 9.76ᵒ (002), and 11.69ᵒ (121), with an additional significant peak at 26ᵒ (2θ), corresponding to the carbon material. Morphological analysis using Field Emission Scanning Electron Microscopy (FE-SEM), and Transmission Electron Microscopy (TEM) demonstrated that the framework has a front particle size of 680 nm and a side particle size of 55±5 nm. High-resolution TEM (HR-TEM) images confirmed the successful attachment of graphene quantum dots (GQDs) onto the NH2-MIL-125 framework. Fourier-Transform Infrared (FT-IR) spectroscopy identified crucial functional groups within the GQD@NH₂-MIL-125 structure, including O-Ti-O metal bonds within the 500 to 700 cm⁻¹ range, and N-H and C-N bonds at 1,646 cm⁻¹ and 1,164 cm⁻¹, respectively. BET isotherm analysis further revealed a specific surface area of 338.1 m²/g and an average pore size of 46.86 nm. This framework also demonstrated UV-active properties, as identified by UV-visible light spectra, and its photoluminescence (PL) spectra showed an emission peak around 430 nm when excited at 350 nm, indicating its potential as a fluorescent drug delivery carrier. In parallel, the cross-shaped M8U6/FM8U6 frameworks were synthesized and characterized using X-ray diffraction, which identified distinct peaks at 2θ = 7.4 (111), 8.5 (200), 9.2 (002), 10.8 (002), 12.1 (220), 16.7 (103), and 17.1 (400). FE-SEM, HR-TEM, and TEM analyses revealed particle sizes of 350±50 nm for M8U6 and 200±50 nm for FM8U6. These frameworks, synthesized from terephthalic acid (H₂BDC), displayed notable vibrational bonds, such as C=O at 1,650 cm⁻¹, Fe-O in MIL-88 at 520 cm⁻¹, and Zr-O in UIO-66 at 482 cm⁻¹. BET analysis showed specific surface areas of 740.1 m²/g with a pore size of 22.92 nm for M8U6 and 493.9 m²/g with a pore size of 35.44 nm for FM8U6. Extended X-ray Absorption Fine Structure (EXAFS) spectra confirmed the stability of Ti-O bonds in the frameworks, with bond lengths of 2.026 Å for MIL-125, 1.962 Å for NH₂-MIL-125, and 1.817 Å for GQD@NH₂-MIL-125. These findings highlight the potential of these organometallic frameworks for enhanced liver cancer therapy through precise drug delivery and imaging, representing a significant advancement in nanomaterial applications in biomedical science.

Keywords: liver cancer cells, metal organic frameworks, Doxorubicin (DOX), drug release.

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Authors: Paul Feyi Waboso

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This case report presents a 57-year-old female patient with a history of colon cancer, colostomy, and immunocompromise, who presented with an unusual bilateral vulval abscess, more prominent on the left side. Due to the atypical presentation, an MRI was performed, revealing a pelvic collection and a fistulous connection between the pelvis and vulva. This finding prompted an urgent surgical intervention. This case highlights the diagnostic and therapeutic challenges of managing complex abscesses and fistulas in immunocompromised patients. Introduction: Vulval abscesses in immunocompromised individuals can present with atypical features and may be associated with complex pathologies. Patients with a history of cancer, colostomy, and immunocompromise are particularly prone to infections and may present with unusual manifestations. This report discusses a case of a large bilateral vulval abscess with an underlying pelvic fistula, emphasizing the importance of advanced imaging in cases with atypical presentations. Case Presentation: A 57-year-old female with a known history of colon cancer, treated with colostomy, presented with severe pain and swelling in the vulval area. Physical examination revealed bilateral vulval swelling, with the abscess on the left side appearing larger and more pronounced than on the right. Given her immunocompromised status and the unusual nature of the presentation, we requested an MRI of the pelvis, suspecting an underlying pathology beyond a typical abscess. Investigations: MRI imaging revealed a significant pelvic collection and identified a fistulous tract between the pelvis and the vulva. This confirmed that the vulval abscess was connected to a deeper pelvic infection, necessitating urgent intervention. Management: After consultation with the multidisciplinary team (MDT), it was agreed that the patient required surgical intervention, having had 48 hours of antibiotics. The patient underwent evacuation of the left-sided vulval abscess under spinal anesthesia. During surgery, the pelvic collection was drained of 200 ml of pus. Outcome and Follow-Up: Postoperative recovery was closely monitored due to the patient’s immunocompromised state. Follow-up imaging and clinical evaluation showed improvement in symptoms, with gradual resolution of infection. The patient was scheduled for regular follow-up visits to monitor for recurrence or further complications. Discussion: Bilateral vulval abscesses are uncommon and, in an immunocompromised patient, warrant thorough investigation to rule out deeper infectious or fistulous connections. This case underscores the utility of MRI in identifying complex fistulous tracts and highlights the importance of a multidisciplinary approach in managing such high-risk patients. Conclusion: This case illustrates a rare presentation of bilateral vulval abscess with an associated pelvic fistula.

Keywords: vulval abscess, MDT team, colon cancer with pelvic fistula, vulval skin condition

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Authors: Muhammad Aasim, Mehmet Karataş, Fatih Erci, Şeyma Bakırcı, Ecenur Korkmaz, Burak Kahveci

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Water hyssop (Bacopa monnieri L. Wettst.) is an important medicinal aquatic/semi aquatic plant native to India where it is used in traditional medicinal system. The plant contains bioactive compounds mainly Bacosides which are the main ingridient of commercial drug available as memory enhancer tonic. The local name of water hyssop is Brahmi and brahmi based drugs are available against for curing chronic diseases and disorders Alzheimer’s disease, anxiety, asthma, cancer, mental illness, respiratory ailments, and stomach ulcers. The plant is not a cultivated plant and collection of plant from nature make palnt threatened to endangered. On the other hand, low seed viability and availability make it difficult to propagate plant through traditional techniques. In recent years, plant tissue culture techniques have been employed to propagate plant for its conservation and production for continuous availability of secondary metabolites. On the other hand, application of nanoparticles has been reported for increasing biomass, in vitro regeneration and secondary metabolites production. In this study, silver nanoparticles (AgNPs) were applied at the rate of 2, 4, 6, 8 and 10 ppm to Murashihe and Skoog (MS) medium supplemented with 1.0 mg/l Benzylaminopurine (BAP), 3.0% sucrose and 0.7% agar. Leaf explants of water hyssop were cultured on AgNPs containing medium. Shoot induction from leaf explants were relatively slow compared to medium without AgNPs. Multiple shoot induction was recorded after 3-4 weeks of culture comapred to control that occured within 10 days. Regenerated shoots were rooted successfully on MS medium supplemented with 1.0 mg/l IBA and acclimatized in the aquariums for further studies.

Keywords: Water hyssop, Silver nanoparticles, In vitro, Regeneration, Secondary metabolites

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Authors: Yasuyuki Takahashi, Hirotaka Shimada, Kyoko Saito

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Bone scintigraphy is widely used as a screening tool for bone metastases. However, the 180 to 240 minutes (min) waiting time after the intravenous (i.v.) injection of the tracer is both long and tiresome. To solve this shortcoming, a bone scan with a shorter waiting time is needed. In this study, we applied the Maximum Intensity Projection (MIP) and triple energy window (TEW) scatter correction to a whole body bone SPECT (Merged SPECT) and investigated shortening the waiting time. Methods: In a preliminary phantom study, hot gels of 99mTc-HMDP were inserted into sets of rods with diameters ranging from 4 to 19 mm. Each rod set covered a sector of a cylindrical phantom. The activity concentration of all rods was 2.5 times that of the background in the cylindrical body of the phantom. In the human study, SPECT images were obtained from chest to abdomen at 30 to 180 min after 99mTc- hydroxymethylene diphosphonate (HMDP) injection of healthy volunteers. For both studies, MIP images were reconstructed. Planar whole body images of the patients were also obtained. These were acquired at 200 min. The image quality of the SPECT and the planar images was compared. Additionally, 36 patients with breast cancer were scanned in the same way. The delectability of uptake regions (metastases) was compared visually. Results: In the phantom study, a 4 mm size hot gel was difficult to depict on the conventional SPECT, but MIP images could recognize it clearly. For both the healthy volunteers and the clinical patients, the accumulation of 99mTc-HMDP in the SPECT was good as early as 90 min. All findings of both image sets were in agreement. Conclusion: In phantoms, images from MIP with TEW scatter correction could detect all rods down to those with a diameter of 4 mm. In patients, MIP reconstruction with TEW scatter correction could improve the detectability of hot lesions. In addition, the time between injection and imaging could be shortened from that conventionally used for whole body scans.

Keywords: merged SPECT, MIP, TEW scatter correction, 99mTc-HMDP

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Authors: A. A. Dehpour, B. Eslami, S. Rezaie, S. F. Hashemian, F. Shafie, M. Kiaie

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The aims of study were investigation on chemical composition essential oil and the effect of extract of Coronilla varia on antimicrobial and cytotoxicity activity. The essential oils of Coronilla varia is obtained by hydrodistillation and analyzed by (GC/MS) for determining their chemical composition and identification of their components. Antibacterial activity of plant extract was determined by disc diffusion method. The effect of hydroalcolic extracts from Cornilla varia investigated on MCF7 cancer cell line by MTT assay. The major components were Caryophyllene Oxide (60.19%), Alphacadinol (4.13%) and Homoadantaneca Robexylic Acid (3.31%). The extracts from Coronilla varia had interesting activity against Proteus mirabilis in the concentration of 700 µg/disc and did not show any activity against Staphylococus aureus, Bacillus subtillis, Klebsiella pneumonia and Entrobacter cloacae. The positive control, Ampicillin, Chloramphenicol and Cenphalothin had shown zone of inhibition resistant all bacteria. Corohilla varia ethanol extract could inhibit the proliferation of MCF7 cell line in RPMI 1640 medium. IC50 5(mg/ml) was the optimum concentration of extract from Coronilla varia inhibition of cell line growth. The MCF7 cancer cell line and Proteus mirabilis were more sensitive to Coronilla varia ethanol extract.

Keywords: Coronilla varia, essential oil, antibacterial, anticancer, hela cell line

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Authors: Alvaro L. Ronco

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Background and purpose: Although our country is a developing one, it has a typical Western meat-rich dietary style. Based on estimates of heme and nonheme iron contents in representative foods, we carried out the present epidemiologic study, with the aim of accurately analyzing dietary iron and its role on CRC risk. Subjects/methods: Patients (611 CRC incident cases and 2394 controls, all belonging to public hospitals of our capital city) were interviewed through a questionnaire including socio-demographic, reproductive and lifestyle variables, and a food frequency questionnaire of 64 items, which asked about food intake 5 years before the interview. The sample included 1937 men and 1068 women. Controls were matched by sex and age (± 5 years) to cases. Food-derived nutrients were calculated from available databases. Total dietary iron was calculated and classified by heme or nonheme source, following data of specific Dutch and Canadian studies, and additionally adjusted by energy. Odds Ratios (OR) and 95% confidence intervals were calculated through unconditional logistic regression, adjusting for relevant potential confounders (education, body mass index, family history of cancer, energy, infusions, and others). A heme/nonheme (H/NH) ratio was created and the interest variables were categorized into tertiles, for analysis purposes. Results: The following risk estimations correspond to the highest tertiles. Total iron intake showed no association with CRC risk neither among men (OR=0.83, ptrend =.18) nor among women (OR=1.48, ptrend =.09). Heme iron was positively associated among men (OR=1.88, ptrend < .001) and for the overall sample (OR=1.44, ptrend =.002), however, it was not associated among women (OR=0.91, ptrend =.83). Nonheme iron showed an inverse association among men (OR=0.53, ptrend < .001) and the overall sample (OR=0.78, ptrend =.04), but was not associated among women (OR=1.46, ptrend =.14). Regarding H/NH ratio, risks increased only among men (OR=2.12, ptrend < .001) but lacked of association among women (OR=0.81, ptrend =.29). Conclusions. We have observed different types of associations between CRC risk and high dietary heme, nonheme and H/NH iron ratio. Therefore, the source of the available iron might be of importance as a link to colorectal carcinogenesis, perhaps pointing to reconsider the animal/plant proportions of this vital mineral within diet. Nevertheless, the different associations observed for each sex, demand further studies in order to clarify these points.

Keywords: chelation, colorectal cancer, heme, iron, nonheme

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Authors: Corina Muscurel, Irina Stoian, Laura Gaman, Valeriu Atanasiu

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Chronic inflammation predisposes cells to neoplastic transformation and is associated with angiogenesis. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) give rise to anti-inflammatory metabolites and decrease some inflammatory cytokines. The aim of the study was to analyze the effect of n-3 PUFAs intake on patients with tumors in early-stage (without regional or distant metastasis). There were two groups of patients: one group with colon tumors and one group with lung tumors. All patients took for 60 days daily supplements from fish-oil containing 600 mg eicosapentaenoic acid and 400 mg docosahexaenoic acid. The plasma markers were evaluated before and after PUFAs intake: ceruloplasmin (using p-phenylenediamine oxidase method), plasma total thiol groups (using dithiobis-nitrobenzoic acid method) and CEA (carcinoembryonic antigen using electrochemiluminescent immunoassay). The results reflect ceruloplasmin decrease (p < 0.05), plasma total thiol groups increase (not statistically significant) and CEA decrease (p < 0.05) after n-3 PUFAs intake. Conclusions: n-3 PUFAs intake is favorable in premalignant lesions or in early tumor stage and dietary fish-oil has anti-inflammatory effects and can contribute to reduce cancer progression.

Keywords: cancer, fish-oil, inflammation, n-3 polyunsaturated fatty acids

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Authors: R. Babi Saraswathi, K. Divya, A. Habeebur Rahman, D. B. Hari Prakash, S. Jayanth, T. Kumar, N. Vijayarangan

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Document automation is the design of systems and workflows, assembling repetitive documents to meet the specific business needs. In any organization or institution, documenting employee’s information is very important for both employees as well as management. It shows an individual’s progress to the management. Many documents of the employee are in the form of papers, so it is very difficult to arrange and for future reference we need to spend more time in getting the exact document. Also, it is very tedious to generate reports according to our needs. The process gets even more difficult on getting approvals and hence lacks its security aspects. This project overcomes the above-stated issues. By storing the details in the database and maintaining the e-documents, the automation system reduces the manual work to a large extent. Then the approval process of some important documents can be done in a much-secured manner by using Digital Signature and encryption techniques. Details are maintained in the database and e-documents are stored in specific folders and generation of various kinds of reports is possible. Moreover, an efficient search method is implemented is used in the database. Automation supporting document maintenance in many aspects is useful for minimize data entry, reduce the time spent on proof-reading, avoids duplication, and reduce the risks associated with the manual error, etc.

Keywords: e-documents, automation, digital signature, encryption

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Authors: C. Lopez, S. Dourdain, G. Arrachart, S. Pellet-Rostaing

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Ionic liquids (ILs) are considered a good alternative for organic solvents in extractive processes; however, the higher or lower extraction efficiency in ILs remains difficult to predict because a lack of understanding of the extraction mechanisms in this class of diluents, making their application difficult to generalize. We have studied the extraction behavior of La(III) and Eu(III) from aqueous solution into n-dodecane and two ionic liquids (ILs), 1-ethyl-1-butylpiperidinium bis (trifluoromethylsulfonyl)imide [EBPip⁺] [NTf₂⁻] and 1-ethyl-1-octylpiperidinium bis (trifluoromethylsulfonyl)imide [EOPip⁺] [NTf₂⁻], at room temperature using N,N’- dimethyl- N,N’-dioctylhexylethoxymalonamide (DMDOHEMA) as extractant. Fe(III) was introduced to the aqueous phase in order to study the selectivity toward La(III) and Eu(III) and the effect of variation of PH was investigated by using of several HNO₃ concentrations. We found that the ionic liquid with shorter alkyl chain [EBPip⁺] [NTf₂⁻] showed a higher extraction ability than [EOPip⁺] [NTf₂⁻] and that the use of ILs as organic solvent instead n-dodecane, greatly enhanced the extraction percentage of the target metals with a good selectivity. Cation ([EBPip⁺] or [EOPip⁺]) and anion ([NTf₂⁻]) concentration in the aqueous phase, has been determined in order to elucidate the extraction mechanism.

Keywords: extraction mechanism, ionic liquids, rare earths elements, solvent extraction

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Authors: Abdul Hafeez, Samiya Shehzadi

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This research paper presents a different approach towards eco-friendly textile design by developing a sustainable composite fabric from orange peel for ladies' undergarments. The research focuses on utilizing orange peel to develop a unique orange leather/composite (fabric) through a process involving heating, extracting, and subsequent sun-drying to obtain the composite. The sustainable composite fabric shows properties that are favorable to the development of environmentally friendly undergarments, which not only offer UV protection but also possess healing properties for the skin. Through comprehensive testing and analysis, it has been determined that the orange peel composite fabric has zero harmful effects on the skin, making it a safe and desirable material for intimate wear. Furthermore, the research suggests that the orange peel composite fabric has the potential to reduce the rate of cancer cell growth. While the exact mechanisms and factors contributing to this effect require further investigation, the initial findings indicate promising aspects of the fabric in terms of potential cancer-preventive properties. Research contribution to the field of sustainable textile design by introducing a usual and eco-friendly approach utilizing orange peel waste. This work opens up avenues for further exploration and development of innovative materials that are both sustainable and beneficial for human health.

Keywords: sustainability, composite textiles, extracting, undergarments, eco-friendly, orange peels

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Authors: Aoxue Yang, Weili Tian, Haikun Liu

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Brain tumor stem cells (BTSCs) are resistant to therapy and give rise to recurrent tumors. These rare and elusive cells are likely to disseminate during cancer progression, and some may enter dormancy, remaining viable but not increasing. The identification of dormant BTSCs is thus necessary to design effective therapies for glioblastoma (GBM) patients. Glucocorticoids (GCs) are used to treat GBM-associated edema. However, glucocorticoids participate in the physiological response to psychosocial stress, linked to poor cancer prognosis. This raises concern that glucocorticoids affect the tumor and BTSCs. Identifying markers specifically expressed by brain tumor stem cells (BTSCs) may enable specific therapies that spare their regular tissue-resident counterparts. By ribosome profiling analysis, we have identified that glycerol-3-phosphate dehydrogenase 1 (GPD1) is expressed by dormant BTSCs but not by NSCs. Through different stress-induced experiments in vitro, we found that only dexamethasone (DEXA) can significantly increase the expression of GPD1 in NSCs. Adversely, mifepristone (MIFE) which is classified as glucocorticoid receptors antagonists, could decrease GPD1 protein level and weaken the proliferation and stemness in BTSCs. Furthermore, DEXA can induce GPD1 expression in tumor-bearing mice brains and shorten animal survival, whereas MIFE has a distinct adverse effect that prolonged mice lifespan. Knocking out GR in NSC can block the upregulation of GPD1 inducing by DEXA, and we find the specific sequences on GPD1 promotor combined with GR, thus improving the efficiency of GPD1 transcription from CHIP-Seq. Moreover, GR and GPD1 are highly co-stained on GBM sections obtained from patients and mice. All these findings confirmed that GR could regulate GPD1 and loss of GPD1 Impairs Multiple Pathways Important for BTSCs Maintenance GPD1 is also a critical enzyme regulating glycolysis and lipid synthesis. We observed that DEXA and MIFE could change the metabolic profiles of BTSCs by regulating GPD1 to shift the transition of cell dormancy. Our transcriptome and lipidomics analysis demonstrated that cell cycle signaling and phosphoglycerides synthesis pathways contributed a lot to the inhibition of GPD1 caused by MIFE. In conclusion, our findings raise concern that treatment of GBM with GCs may compromise the efficacy of chemotherapy and contribute to BTSC dormancy. Inhibition of GR can dramatically reduce GPD1 and extend the survival duration of GBM-bearing mice. The molecular link between GPD1 and GR may give us an attractive therapeutic target for glioblastoma.

Keywords: cancer stem cell, dormancy, glioblastoma, glycerol-3-phosphate dehydrogenase 1, glucocorticoid receptor, dexamethasone, RNA-sequencing, phosphoglycerides

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Authors: Shenlun Chen, Leonard Wee

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Tumor grading is an essential reference for colorectal cancer (CRC) staging and survival prognostication. The widely used World Health Organization (WHO) grading system defines histological grade of CRC adenocarcinoma based on the density of glandular formation on whole slide images (WSI). Tumors are classified as well-, moderately-, poorly- or un-differentiated depending on the percentage of the tumor that is gland forming; >95%, 50-95%, 5-50% and <5%, respectively. However, manually grading WSIs is a time-consuming process and can cause observer error due to subjective judgment and unnoticed regions. Furthermore, pathologists’ grading is usually coarse while a finer and continuous differentiation grade may help to stratifying CRC patients better. In this study, a deep learning based automatic differentiation grading algorithm was developed and evaluated by survival analysis. Firstly, a gland segmentation model was developed for segmenting gland structures. Gland regions of WSIs were delineated and used for differentiation annotating. Tumor regions were annotated by experienced pathologists into high-, medium-, low-differentiation and normal tissue, which correspond to tumor with clear-, unclear-, no-gland structure and non-tumor, respectively. Then a differentiation prediction model was developed on these human annotations. Finally, all enrolled WSIs were processed by gland segmentation model and differentiation prediction model. The differentiation grade can be calculated by deep learning models’ prediction of tumor regions and tumor differentiation status according to WHO’s defines. If multiple WSIs were possessed by a patient, the highest differentiation grade was chosen. Additionally, the differentiation grade was normalized into scale between 0 to 1. The Cancer Genome Atlas, project COAD (TCGA-COAD) project was enrolled into this study. For the gland segmentation model, receiver operating characteristic (ROC) reached 0.981 and accuracy reached 0.932 in validation set. For the differentiation prediction model, ROC reached 0.983, 0.963, 0.963, 0.981 and accuracy reached 0.880, 0.923, 0.668, 0.881 for groups of low-, medium-, high-differentiation and normal tissue in validation set. Four hundred and one patients were selected after removing WSIs without gland regions and patients without follow up data. The concordance index reached to 0.609. Optimized cut off point of 51% was found by “Maxstat” method which was almost the same as WHO system’s cut off point of 50%. Both WHO system’s cut off point and optimized cut off point performed impressively in Kaplan-Meier curves and both p value of logrank test were below 0.005. In this study, gland structure of WSIs and differentiation status of tumor regions were proven to be predictable through deep leaning method. A finer and continuous differentiation grade can also be automatically calculated through above models. The differentiation grade was proven to stratify CAC patients well in survival analysis, whose optimized cut off point was almost the same as WHO tumor grading system. The tool of automatically calculating differentiation grade may show potential in field of therapy decision making and personalized treatment.

Keywords: colorectal cancer, differentiation, survival analysis, tumor grading

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Authors: Nigar Kantarci Carsibasi

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Coarse-grained elastic network models, namely Gaussian network model (GNM) and Anisotropic network model (ANM), are utilized in order to investigate the fluctuation dynamics of Murine Double Minute 2 (MDM2), which is the native inhibitor of p53. Conformational dynamics of MDM2 are elucidated in unbound, p53 bound, and non-peptide small molecule inhibitor bound forms. With this, it is aimed to gain insights about the alterations brought to global dynamics of MDM2 by native peptide inhibitor p53, and two small molecule inhibitors (HDM201 and NVP-CGM097) that are undergoing clinical stages in cancer studies. MDM2 undergoes significant conformational changes upon inhibitor binding, carrying pieces of evidence of induced-fit mechanism. Small molecule inhibitors examined in this work exhibit similar fluctuation dynamics and characteristic mode shapes with p53 when complexed with MDM2, which would shed light on the design of novel small molecule inhibitors for cancer therapy. The results showed that residues Phe 19, Trp 23, Leu 26 reside in the minima of slowest modes of p53, pointing to the accepted three-finger binding model. Pro 27 displays the most significant hinge present in p53 and comes out to be another functionally important residue. Three distinct regions are identified in MDM2, for which significant conformational changes are observed upon binding. Regions I (residues 50-77) and III (residues 90-105) correspond to the binding interface of MDM2, including (α2, L2, and α4), which are stabilized during complex formation. Region II (residues 77-90) exhibits a large amplitude motion, being highly flexible, both in the absence and presence of p53 or other inhibitors. MDM2 exhibits a scattered profile in the fastest modes of motion, while binding of p53 and inhibitors puts restraints on MDM2 domains, clearly distinguishing the kinetically hot regions. Mode shape analysis revealed that the α4 domain controls the size of the cleft by keeping the cleft narrow in unbound MDM2; and open in the bound states for proper penetration and binding of p53 and inhibitors, which points to the induced-fit mechanism of p53 binding. P53 interacts with α2 and α4 in a synchronized manner. Collective modes are shifted upon inhibitor binding, i.e., second mode characteristic motion in MDM2-p53 complex is observed in the first mode of apo MDM2; however, apo and bound MDM2 exhibits similar features in the softest modes pointing to pre-existing modes facilitating the ligand binding. Although much higher amplitude motions are attained in the presence of non-peptide small molecule inhibitor molecules as compared to p53, they demonstrate close similarity. Hence, NVP-CGM097 and HDM201 succeed in mimicking the p53 behavior well. Elucidating how drug candidates alter the MDM2 global and conformational dynamics would shed light on the rational design of novel anticancer drugs.

Keywords: cancer, drug design, elastic network model, MDM2

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Authors: Felipa de Mello-Sampayo

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The aim of this study is to undertake, from patient’s perspective, the timing and probability of using teledermatology, comparing it with a conventional referral system. The dynamic stochastic model’s main value-added consists of the concrete application to patients waiting for dermatology surgical intervention. Patients with low health level uncertainty must use teledermatology treatment as soon as possible, which is precisely when the teledermatology is least valuable. The results of the model were then tested empirically with the teledermatology network covering the area served by the Hospital Garcia da Horta, Portugal, links the primary care centers of 24 health districts with the hospital’s dermatology department via the corporate intranet of the Portuguese healthcare system. Health level volatility can be understood as the hazard of developing skin cancer and the trend of health level as the bias of developing skin lesions. The results of the survival analysis suggest that the theoretical model can explain the use of teledermatology. It depends negatively on the volatility of patients' health, and positively on the trend of health, i.e., the lower the risk of developing skin cancer and the younger the patients, the more presurgical teledermatology one expects to occur. Presurgical teledermatology also depends positively on out-of-pocket expenses and negatively on the opportunity costs of teledermatology, i.e., the lower the benefit missed by using teledermatology, the more presurgical teledermatology one expects to occur.

Keywords: teledermatology, wait time, uncertainty, opportunity cost, survival analysis

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Authors: Nabil Saad, David Morgan, Manish Gupta

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Visibility has become a key component of air quality and is regulated in many areas by environmental laws such as the EPA Clean Air Act and Regional Haze Rule. Typically, visibility is calculated by estimating the optical absorption and scattering of both gases and aerosols. A major component of the aerosols’ climatic effect is due to their scattering and absorption of solar radiation, which are governed by their optical and physical properties. However, the accurate assessment of this effect on global warming, climate change, and air quality is made difficult due to uncertainties in the calculation of single scattering albedo (SSA). Experimental complications arise in the determination of the single scattering albedo of an aerosol particle since it requires the simultaneous measurement of both scattering and extinction. In fact, aerosol optical absorption, in particular, is a difficult measurement to perform, and it’s often associated with large uncertainties when using filter methods or difference methods. In this presentation, we demonstrate the use of a new open-path Optical Extinction Analyzer (OEA) in conjunction with a nephelometer and two particle sizers, emphasizing the benefits that co-employment of the OEA offers to derive the complex refractive index of aerosols and their single scattering albedo parameter. Various use cases, data reproducibility, and instrument calibration will also be presented to highlight the value proposition of this novel Open-Path OEA.

Keywords: aerosols, extinction, visibility, albedo

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Authors: Kamila Dus-Szachniewicz, Artur Bednarkiewicz, Katarzyna Gdesz-Birula, Slawomir Drobczynski

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In modern oncology hyperthermia (HT) is defined as a controlled tumor heating. HT treatment temperatures range between 40–48 °C and can selectively damage heat-sensitive cancer cells or limit their further growth, usually with minimal injury to healthy tissues. Despite many advantages, conventional whole-body and regional hyperthermia have clinically relevant side effects, including cardiac and vascular disorders. Additionally, the lack of accessibility of deep-seated tumor sites and impaired targeting micrometastases renders HT less effective. It is believed that above disadvantages can significantly overcome by the application of biofunctionalized microparticles, which can specifically target tumor sites and become activated by an external stimulus to provide a sufficient cellular response. In our research, the unique optical tweezers system have enabled capturing the silica microparticles, primary cells and tumor spheroids in highly controllable and reproducible environment to study the impact of localized heat stimulation on normal and pathological cell and within multicellular tumor spheroid. High throughput spheroid model was introduced to better mimic the response to HT treatment on tumors in vivo. Additionally, application of local heating of tumor spheroids was performed in strictly controlled conditions resembling tumor microenvironment (temperature, pH, hypoxia, etc.), in response to localized and nonhomogeneous hyperthermia in the extracellular matrix, which promotes tumor progression and metastatic spread. The lack of precise control over these well- defined parameters in basic research leads to discrepancies in the response of tumor cells to the new treatment strategy in preclinical animal testing. The developed approach enables also sorting out subclasses of cells, which exhibit partial or total resistance to therapy, in order to understand fundamental aspects of the resistance shown by given tumor cells in response to given therapy mode and conditions. This work was funded by the National Science Centre (NCN, Poland) under grant no. UMO-2017/27/B/ST7/01255.

Keywords: cancer spheroids, hyperthermia, microparticles, optical tweezers

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Authors: H. S. Niroshani, W. M. Ediri Arachchi, R. Tudugala, U. J. M. A. L. Jayasinghe, U. M. U. J. Jayasekara, P. B. Hewavithana

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Mammography is used as a screening tool for early diagnosis of breast cancer. It is also useful in refining the diagnosis of breast cancer either by assessment or work up after a suspicious area in the breast has been detected. In order to detect breast cancer accurately and at the earliest possible stage, the image must have an optimum contrast to reveal mass densities and spiculated fibrous structures radiating from them. In addition, the spatial resolution must be adequate to reveal the suffusion of micro calcifications and their shape. The above factors can be optimized by implementing an effective QA programme to enhance the accurate diagnosis of mammographic imaging. Therefore, the radiographer’s knowledge on QA is greatly instrumental in routine mammographic practice. The aim of this study was to assess the radiographer’s knowledge on Quality Assurance and Quality Control programmes in relation to mammographic procedures. A cross-sectional study was carried out among all radiographers working in each mammography setting in Sri Lanka. Pre-tested, anonymous self-administered questionnaires were circulated among the study population and duly filled questionnaires returned within a period of three months were taken into the account. The data on demographical information, knowledge on QA programme and associated QC tests, overall knowledge on QA and QC programmes were obtained. Data analysis was performed using IBM SPSS statistical software (version 20.0). The total response rate was 59.6% and the average knowledge score was 54.15±11.29 SD out of 100. Knowledge was compared on the basis of education level, special training of mammography, and the years of working experience in a mammographic setting of the individuals. Out of 31 subjects, 64.5% (n=20) were graduate radiographers and 35.5% (n=11) were diploma holders while 83.9% (n=26) of radiographers have been specially trained for mammography and 16.1% (n=5) have not been attended for any special training for mammography. It is also noted that 58.1% (n=18) of individuals possessed their experience of less than one year and rest 41.9% (n=13) of them were greater than that. Further, the results found that there is a significant difference (P < 0.05) in the knowledge of QA and overall knowledge on QA and QC programme in the categories of education level and working experience. Also, results imply that there was a significant difference (P < 0.05) in the knowledge of QC test among the groups of trained and non-trained radiographers. This study reveals that education level, working experience and the training obtained particularly in the field of mammography have a significant impact on their knowledge on QA and QC in mammography.

Keywords: knowledge, mammography, quality assurance, quality control

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Authors: Inna Kornienko, Svetlana Guryeva, Natalia Danilova, Elena Petersen

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Drug toxicity often goes undetected until clinical trials, the most expensive and dangerous phase of drug development. Both human cell culture and animal studies have limitations that cannot be overcome by improvements in drug testing protocols. Tissue engineering is an emerging alternative approach to creating models of human malignant tumors for experimental oncology, personalized medicine, and drug discovery studies. This new generation of bioengineered tumors provides an opportunity to control and explore the role of every component of the model system including cell populations, supportive scaffolds, and signaling molecules. An area that could greatly benefit from these models is cancer research. Recent advances in tissue engineering demonstrated that decellularized tissue is an excellent scaffold for tissue engineering. Decellularization of donor organs such as heart, liver, and lung can provide an acellular, naturally occurring three-dimensional biologic scaffold material that can then be seeded with selected cell populations. Preliminary studies in animal models have provided encouraging results for the proof of concept. Decellularized Organs preserve organ microenvironment, which is critical for cancer metastasis. Utilizing 3D tumor models results greater proximity of cell culture morphological characteristics in a model to its in vivo counterpart, allows more accurate simulation of the processes within a functioning tumor and its pathogenesis. 3D models allow study of migration processes and cell proliferation with higher reliability as well. Moreover, cancer cells in a 3D model bear closer resemblance to living conditions in terms of gene expression, cell surface receptor expression, and signaling. 2D cell monolayers do not provide the geometrical and mechanical cues of tissues in vivo and are, therefore, not suitable to accurately predict the responses of living organisms. 3D models can provide several levels of complexity from simple monocultures of cancer cell lines in liquid environment comprised of oxygen and nutrient gradients and cell-cell interaction to more advanced models, which include co-culturing with other cell types, such as endothelial and immune cells. Following this reasoning, spheroids cultivated from one or multiple patient-derived cell lines can be utilized to seed the matrix rather than monolayer cells. This approach furthers the progress towards personalized medicine. As an initial step to create a new ex vivo tissue engineered model of a cancer tumor, optimized protocols have been designed to obtain organ-specific acellular matrices and evaluate their potential as tissue engineered scaffolds for cultures of normal and tumor cells. Decellularized biomatrix was prepared from animals’ kidneys, urethra, lungs, heart, and liver by two decellularization methods: perfusion in a bioreactor system and immersion-agitation on an orbital shaker with the use of various detergents (SDS, Triton X-100) in different concentrations and freezing. Acellular scaffolds and tissue engineered constructs have been characterized and compared using morphological methods. Models using decellularized matrix have certain advantages, such as maintaining native extracellular matrix properties and biomimetic microenvironment for cancer cells; compatibility with multiple cell types for cell culture and drug screening; utilization to culture patient-derived cells in vitro to evaluate different anticancer therapeutics for developing personalized medicines.

Keywords: 3D models, decellularization, drug discovery, drug toxicity, scaffolds, spheroids, tissue engineering

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Authors: Abdulrahman M. Qahtani, Gary. B. Wills, Andy. M. Gravell

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Communicating and managing customers’ requirements in software development projects play a vital role in the software development process. While it is difficult to do so locally, it is even more difficult to communicate these requirements over distributed boundaries and to convey them to multiple distribution customers. This paper discusses the communication of multiple distribution customers’ requirements in the context of customised software products. The main purpose is to understand the challenges of communicating and managing customisation requirements across distributed boundaries. We propose a model for Communicating Customisation Requirements of Multi-Clients in a Distributed Domain (CCRD). Thereafter, we evaluate that model by presenting the findings of a case study conducted with a company with customisation projects for 18 distributed customers. Then, we compare the outputs of the real case process and the outputs of the CCRD model using simulation methods. Our conjecture is that the CCRD model can reduce the challenge of communication requirements over distributed organisational boundaries, and the delay in decision making and in the entire customisation process time.

Keywords: customisation software products, global software engineering, local decision making, requirement engineering, simulation model

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Authors: Douglas Dunn, Ricahrd Walton, Matthew Warner-Smith, Chirag Mistry, Kan Ren, David Roder

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Introduction: Breast density is a risk factor for breast cancer, both due to increased fibro glandular tissue that can harbor malignancy and the masking of lesions on mammography. Therefore, evaluation of breast density measurement is useful for risk stratification on an individual and population level. This study investigates the performance of Lunit INSIGHT MMG for automated breast density measurement. We analyze the reliability of Lunit compared to breast radiologists, explore density variations across the BreastScreen NSW population, and examine the impact of breast implants on density measurements. Methods: 15,518 mammograms were utilized for a comparative analysis of intra- and inter-reader reliability between Lunit INSIGHT MMG and breast radiologists. Subsequently, Lunit was used to evaluate 624,113 mammograms for investigation of density variations according to age and birth country, providing insights into diverse population subgroups. Finally, we compared breast density in 4,047 clients with implants to clients without implants, controlling for age and birth country. Results: Inter-reader variability between Lunit and Breast Radiologists weighted kappa coefficient was 0.72 (95%CI 0.71-0.73). Highest breast densities were seen in women with a North-East Asia background, whilst those of Aboriginal background had the lowest density. Across all backgrounds, density was demonstrated to reduce with age, though at different rates according to country of birth. Clients with implants had higher density relative to the age-matched no-implant strata. Conclusion: Lunit INSIGHT MMG demonstrates reasonable inter- and intra-observer reliability for automated breast density measurement. The scale of this study is significantly larger than any previous study assessing breast density due to the ability to process large volumes of data using AI. As a result, it provides valuable insights into population-level density variations. Our findings highlight the influence of age, birth country, and breast implants on density, emphasizing the need for personalized risk assessment and screening approaches. The large-scale and diverse nature of this study enhances the generalisability of our results, offering valuable information for breast cancer screening programs internationally.

Keywords: breast cancer, screening, breast density, artificial intelligence, mammography

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Authors: Roberto Coppo, Francesca Orso, Daniela Dettori, Elena Quaglino, Lei Nie, Mehran M. Sadeghi, Daniela Taverna

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Malignant melanoma is currently the fifth most common cancer in the white population and it is fatal in its metastatic stage. Several research studies in recent years have provided evidence that cancer initiation and progression are driven by genetic alterations of the tumor and paracrine interactions between tumor and microenvironment. Scattered data show that the Endothelial and Smooth muscle cell-Derived Neuropilin-like molecule (ESDN) controls cell proliferation and movement of stroma and tumor cells. To investigate the role of ESDN in the tumor microenvironment during melanoma progression, murine melanoma cells (B16 or B16-F10) were injected in ESDN knockout mice in order to evaluate how the absence of ESDN in stromal cells could influence melanoma progression. While no effect was found on primary tumor growth, increased cell extravasation and lung metastasis formation was observed in ESDN knockout mice compared to wild type controls. In order to understand how cancer cells cross the endothelial barrier during metastatic dissemination in an ESDN-null microenvironment, structure, and permeability of lung blood vessels were analyzed. Interestingly, ESDN knockout mice showed structurally altered and more permeable vessels compared to wild type animals. Since cell surface molecules mediate the process of tumor cell extravasation, the expression of a panel of extravasation-related ligands and receptors was analyzed. Importantly, modulations of N-cadherin, E-selectin, ICAM-1 and VAP-1 were observed in ESDN knockout endothelial cells, suggesting the presence of a favorable tumor microenvironment which facilitates melanoma cell extravasation and metastasis formation in the absence of ESDN. Furthermore, a potential contribution of immune cells in tumor dissemination was investigated. An increased recruitment of macrophages in the lungs of ESDN knockout mice carrying subcutaneous B16-F10 tumors was found. In conclusion, our data suggest a functional role of ESDN in the tumor microenvironment during melanoma progression and the identification of the mechanisms that regulate tumor cell extravasation could lead to the development of new therapies to reduce metastasis formation.

Keywords: melanoma, tumor microenvironment, extravasation, cell surface molecules

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Authors: Almudena Espin Perez, Tyler Risom, Carl Pelz, Isabel English, Robert M. Angelo, Rosalie Sears, Andrew J. Gentles

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Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly malignancies. The role of the tumor microenvironment (TME) is gaining significant attention in cancer research. Despite ongoing efforts, the nature of the interactions between tumors, immune cells, and stromal cells remains poorly understood. The cell-intrinsic properties that govern cell lineage plasticity in PDAC and extrinsic influences of immune populations require technically challenging approaches due to the inherently heterogeneous nature of PDAC. Understanding the cell lineage plasticity of PDAC will improve the development of novel strategies that could be translated to the clinic. Members of the team have demonstrated that the acquisition of ductal to neuroendocrine lineage plasticity in PDAC confers therapeutic resistance and is a biomarker of poor outcomes in patients. Our approach combines computational methods for deconvolving bulk transcriptomic cancer data using CIBERSORTx and high-throughput single-cell imaging using Multiplexed Ion Beam Imaging (MIBI) to study lineage plasticity in PDAC and its relationship to the infiltrating immune system. The CIBERSORTx algorithm uses signature matrices from immune cells and stroma from sorted and single-cell data in order to 1) infer the fractions of different immune cell types and stromal cells in bulked gene expression data and 2) impute a representative transcriptome profile for each cell type. We studied a unique set of 300 genomically well-characterized primary PDAC samples with rich clinical annotation. We deconvolved the PDAC transcriptome profiles using CIBERSORTx, leveraging publicly available single-cell RNA-seq data from normal pancreatic tissue and PDAC to estimate cell type proportions in PDAC, and digitally reconstruct cell-specific transcriptional profiles from our study dataset. We built signature matrices and optimized by simulations and comparison to ground truth data. We identified cell-type-specific transcriptional programs that contribute to cancer cell lineage plasticity, especially in the ductal compartment. We also studied cell differentiation hierarchies using CytoTRACE and predict cell lineage trajectories for acinar and ductal cells that we believe are pinpointing relevant information on PDAC progression. Collaborators (Angelo lab, Stanford University) has led the development of the Multiplexed Ion Beam Imaging (MIBI) platform for spatial proteomics. We will use in the very near future MIBI from tissue microarray of 40 PDAC samples to understand the spatial relationship between cancer cell lineage plasticity and stromal cells focused on infiltrating immune cells, using the relevant markers of PDAC plasticity identified from the RNA-seq analysis.

Keywords: deconvolution, imaging, microenvironment, PDAC

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Authors: Eashwar V. Somasundaram, Raoul R. Wadhwa, Jacob G. Scott

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The use of radiomics in measuring geometric properties of tumor images such as size, surface area, and volume has been invaluable in assessing cancer diagnosis, treatment, and prognosis. In addition to analyzing geometric properties, radiomics would benefit from measuring topological properties using persistent homology. Intuitively, features uncovered by persistent homology may correlate to tumor structural features. One example is necrotic cavities (corresponding to 2D topological features), which are markers of very aggressive tumors. We develop a data pipeline in R that clusters tumors images based on persistent homology is used to identify meaningful clinical distinctions between tumors and possibly new relationships not captured by established clinical categorizations. A preliminary analysis was performed on 16 Magnetic Resonance Imaging (MRI) breast tissue segments downloaded from the 'Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging and Molecular Analysis' (I-SPY TRIAL or ISPY1) collection in The Cancer Imaging Archive. Each segment represents a patient’s breast tumor prior to treatment. The ISPY1 dataset also provided the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status data. A persistent homology matrix up to 2-dimensional features was calculated for each of the MRI segmentation. Wasserstein distances were then calculated between all pairwise tumor image persistent homology matrices to create a distance matrix for each feature dimension. Since Wasserstein distances were calculated for 0, 1, and 2-dimensional features, three hierarchal clusters were constructed. The adjusted Rand Index was used to see how well the clusters corresponded to the ER/PR/HER2 status of the tumors. Triple-negative cancers (negative status for all three receptors) significantly clustered together in the 2-dimensional features dendrogram (Adjusted Rand Index of .35, p = .031). It is known that having a triple-negative breast tumor is associated with aggressive tumor growth and poor prognosis when compared to non-triple negative breast tumors. The aggressive tumor growth associated with triple-negative tumors may have a unique structure in an MRI segmentation, which persistent homology is able to identify. This preliminary analysis shows promising results in the use of persistent homology on tumor imaging to assess the severity of breast tumors. The next step is to apply this pipeline to other tumor segment images from The Cancer Imaging Archive at different sites such as the lung, kidney, and brain. In addition, whether other clinical parameters, such as overall survival, tumor stage, and tumor genotype data are captured well in persistent homology clusters will be assessed. If analyzing tumor MRI segments using persistent homology consistently identifies clinical relationships, this could enable clinicians to use persistent homology data as a noninvasive way to inform clinical decision making in oncology.

Keywords: cancer biology, oncology, persistent homology, radiomics, topological data analysis, tumor imaging

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Authors: Ľudmila Ballová, Slavomír Kurhajec, Eva Petrovová, Jarmila Eftimová

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Angiogenesis, a formation of new blood vessels from a pre-existing vasculature, plays an important role in pathologic processes such as the growth and metastasis of tumours. Tumours cannot grow beyond a few millimetres without blood supply from the newly formed blood vessels from the host tissue, a process called tumour-induced angiogenesis. The successful research of antiangiogenic treatment of cancer has focused on nutraceuticals with angiogenesis-modulating properties. Berberine, as a major active component of the bark of Phellodendron amurense Rupr., has shown antitumour activity by intervening into different steps of carcinogenesis. The influence of ethanolic extract of Phellodendron amurese bark on the angiogenesis was tested in vivo on chick chorioallantoic membrane (CAM). The irritancy of the CAM after the application of the crude bark extract dissolved in normal saline (10 mg/mL) was investigated on embryonic day 7. No significant signs of the irritancy, such as vasoconstriction, hyperaemia, haemorrhage or coagulation were observed which indicates the harmless character of the extract. A significant reduction in vessel sprouting and higher percentage of avascular zone was observed in the case of CAM treated with the extract in comparison with non-treated CAM (control), which is a proof of the antiangiogenic potential of the extract. These results could contribute to the development of novel drugs for the treatment of cancer or other diseases, in which angiogenesis plays a significant role.

Keywords: angiogenesis, berberine, chorioallantoic membrane, irritancy, phellodendron amurense

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