Search results for: cancer of the breast
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 2248

Search results for: cancer of the breast

1288 Managing Incomplete PSA Observations in Prostate Cancer Data: Key Strategies and Best Practices for Handling Loss to Follow-Up and Missing Data

Authors: Madiha Liaqat, Rehan Ahmed Khan, Shahid Kamal

Abstract:

Multiple imputation with delta adjustment is a versatile and transparent technique for addressing univariate missing data in the presence of various missing mechanisms. This approach allows for the exploration of sensitivity to the missing-at-random (MAR) assumption. In this review, we outline the delta-adjustment procedure and illustrate its application for assessing the sensitivity to deviations from the MAR assumption. By examining diverse missingness scenarios and conducting sensitivity analyses, we gain valuable insights into the implications of missing data on our analyses, enhancing the reliability of our study's conclusions. In our study, we focused on assessing logPSA, a continuous biomarker in incomplete prostate cancer data, to examine the robustness of conclusions against plausible departures from the MAR assumption. We introduced several approaches for conducting sensitivity analyses, illustrating their application within the pattern mixture model (PMM) under the delta adjustment framework. This proposed approach effectively handles missing data, particularly loss to follow-up.

Keywords: loss to follow-up, incomplete response, multiple imputation, sensitivity analysis, prostate cancer

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1287 Targeting Methionine Metabolism In Gastric Cancer; Promising To Improve Chemosensetivity With Non-hetrogeneity

Authors: Nigatu Tadesse, Li Juan, Liuhong Ming

Abstract:

Gastric cancer (GC) is the fifth most common and fourth deadly cancer in the world with limited treatment options at late advanced stage in which surgical therapy is not recommended with chemotherapy remain as the mainstay of treatment. However, the occurrence of chemoresistance as well as intera-tumoral and inter-tumoral heterogeneity of response to targeted and immunotherapy underlined a clear unmet treatment need in gastroenterology. Several molecular and cellular alterations ascribed for chemo resistance in GC including cancer stem cells (CSC) and tumor microenvironment (TME) remodeling. Cancer cells including CSC bears higher metabolic demand and major changes in TME involves alterations of gut microbiota interacting with nutrients metabolism. Metabolic upregulation in lipids, carbohydrates, amino acids, fatty acids biosynthesis pathways identified as a common hall mark in GC. Metabolic addiction to methionine metabolism occurs in many cancer cells to promote the biosynthesis of S-Adenosylmethionine (SAM), a universal methyl donor molecule for high rate of transmethylation in GC and promote cell proliferation. Targeting methionine metabolism found to promotes chemo-sensitivity with treatment non-heterogeneity. Methionine restriction (MR) promoted the arrest of cell cycle at S/G2 phase and enhanced downregulation of GC cells resistance to apoptosis (including ferroptosis), which suggests the potential of synergy with chemotherapies acting at S-phase of the cell cycle as well as inducing cell apoptosis. Accumulated evidences showed both the biogenesis as well as intracellular metabolism of exogenous methionine could be safe and effective target for therapy either alone or in combination with chemotherapies. This review article provides an over view of the upregulation in methionine biosynthesis pathway and the molecular signaling through the PI3K/Akt/mTOR-c-MYC axis to promote metabolic reprograming through activating the expression of L-type aminoacid-1 (LAT1) transporter and overexpression of Methionine adenosyltransferase 2A(MAT2A) for intercellular metabolic conversion of exogenous methionine to SAM in GC, and the potential of targeting with novel therapeutic agents such as methioninase (METase), Methionine adenosyltransferase 2A (MAT2A), c-MYC, methyl like transferase 16 (METTL16) inhibitors that are currently under clinical trial development stages and future perspectives.

Keywords: gastric cancer, methionine metabolism, pi3k/akt/mtorc1-c-myc axis, gut microbiota, MAT2A, c-MYC, METTL16, methioninase

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1286 Engineering a Tumor Extracellular Matrix Towards an in vivo Mimicking 3D Tumor Microenvironment

Authors: Anna Cameron, Chunxia Zhao, Haofei Wang, Yun Liu, Guang Ze Yang

Abstract:

Since the first publication in 1775, cancer research has built a comprehensive understanding of how cellular components of the tumor niche promote disease development. However, only within the last decade has research begun to establish the impact of non-cellular components of the niche, particularly the extracellular matrix (ECM). The ECM, a three-dimensional scaffold that sustains the tumor microenvironment, plays a crucial role in disease progression. Cancer cells actively deregulate and remodel the ECM to establish a tumor-promoting environment. Recent work has highlighted the need to further our understanding of the complexity of this cancer-ECM relationship. In vitro models use hydrogels to mimic the ECM, as hydrogel matrices offer biological compatibility and stability needed for long term cell culture. However, natural hydrogels are being used in these models verbatim, without tuning their biophysical characteristics to achieve pathophysiological relevance, thus limiting their broad use within cancer research. The biophysical attributes of these gels dictate cancer cell proliferation, invasion, metastasis, and therapeutic response. Evaluating the three most widely used natural hydrogels, Matrigel, collagen, and agarose gel, the permeability, stiffness, and pore-size of each gel were measured and compared to the in vivo environment. The pore size of all three gels fell between 0.5-6 µm, which coincides with the 0.1-5 µm in vivo pore size found in the literature. However, the stiffness for hydrogels able to support cell culture ranged between 0.05 and 0.3 kPa, which falls outside the range of 0.3-20,000 kPa reported in the literature for an in vivo ECM. Permeability was ~100x greater than in vivo measurements, due in large part to the lack of cellular components which impede permeation. Though, these measurements prove important when assessing therapeutic particle delivery, as the ECM permeability decreased with increasing particle size, with 100 nm particles exhibiting a fifth of the permeability of 10 nm particles. This work explores ways of adjusting the biophysical characteristics of hydrogels by changing protein concentration and the trade-off, which occurs due to the interdependence of these factors. The global aim of this work is to produce a more pathophysiologically relevant model for each tumor type.

Keywords: cancer, extracellular matrix, hydrogel, microfluidic

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1285 Anti-Cancerous Activity of Sargassum siliquastrum in Cervical Cancer: Choreographing the Fly's Danse Macabre

Authors: Sana Abbasa, Shahzad Bhattiab, Nadir Khan

Abstract:

Sargassum siliquastrum is brown seaweed with traditional claims for some medicinal properties. This research was done to investigate the methanol extract of S. siliquastrum for antiproliferative activity against human cervical cancer cell line, HeLa and its mode of cell death. From methylene blue assay, S. siliquastrum exhibited antiproliferative activity on HeLa cells with IC50 of 3.87 µg/ml without affecting non-malignant cells. Phase contrast microscopy indicated the confluency reduction in HeLa cells and changes on the cell shape. Nuclear staining with Hoechst 33258 displayed the formation of apoptotic bodies and fragmented nuclei. S. siliquastrum also induced early apoptosis event in HeLa cells as confirmed by FITC-Annexin V/propidium iodide staining by flow cytometry analysis. Cell cycle analysis indicated growth arrest of HeLa cells at G1/S phase. Protein study by flow cytometry indicated the increment of p53, slight increase of Bax and unchanged level of Bcl-2. In conclusion, S. siliquastrum demonstrated an antiproliferative activity in HeLa cell by inducing G1/S cell cycle arrest via p53-mediated pathway.

Keywords: sargassum siliquastrum, cervical cancer, P53, antiproleferation

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1284 Biosynthesis of Selenium Oxide Nanoparticles by Streptomyces bikiniensis and Its Cytotoxicity as Antitumor Agents against Hepatocellular and Breast Cells Carcinoma

Authors: Maged Syed Ahamd, Manal Mohamed Yasser, Essam Sholkamy

Abstract:

In this paper, we reported that selenium (Se) nanoparticles were firstly biosynthesized with a simple and eco-friendly biological method. Their shape, size, FTIR (Fourier Transform Infrared spectroscopy), UV–vis spectra, TEM (Transmission Electron Microscopy) images and EDS (Energy Dispersive Spectroscopy) pattern have been analyzed. TEM analyses of the samples obtained at different stages indicated that the formation of these Se nanostructures was governed by an incubation time (12- 24- 48 hours). The Se nanoparticles were initially generated and then would transform into crystal seeds for the subsequent growth of nanowires; however obtaining stable Se nanowire with a diameter of about 15-100 nm. EDS shows that Se nanoparticles are entirely pure. The IR spectra showed the peaks at 550 cm-1, 1635 cm-1, 1994 cm-1 and 3430 cm-1 correspond to the presence of Se-O bending and stretching vibrations. The concentrations of Se-NPs (0, 1, 2, 5 µg/ml) did not give significantly effect on both two cell lines while the highest concentrations (10- 100 µg/ml gave significantly effects on them. The lethal dose (ID50%) of Se-NPs on Hep2 G and MCF-7 cells was obtained at 75.96 and 61.86 µg/ml, respectively. Results showed that Se nanoparticles as anticancer agent against MCF-7 cells were more effective than Hep2 G cells. Our results suggest that Se-NPs may be a candidate for further evaluation as a chemotherapeutic agent for breast and liver cancers.

Keywords: selenium nanoparticle, Streptomyces bikiniensis, nanowires, chemotherapeutic agent

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1283 Upconversion Nanomaterials for Applications in Life Sciences and Medicine

Authors: Yong Zhang

Abstract:

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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1282 Collision Tumor of Plasmacytoma with Hematological and Non-Hematological Malignancies

Authors: Arati Inamdar, Siddharth Bhattacharyya, Kester Haye

Abstract:

Collision tumors are rare entities characterized by neoplasms of two different cell populations with distinct separating boundaries. Such tumors could be benign, malignant, or a combination of both. The exact mechanism of origin for collision tumors is predicted to be tumor heterogeneity or concurrent occurrence of neoplasm in the same organ. We present two cases of plasmacytoma presenting as a collision tumor, one with a tumor of hematological origin and another with a non-hematological origin, namely Chronic Lymphocytic Leukemia and Adenocarcinoma of the colon, respectively. The immunohistochemical stains and flowcytometry analysis performed on the specimens aided incorrect diagnosis. Interestingly, neoplastic cells of plasmacytoma in the first case demonstrated strong cytokeratin along with weak Epithelial Specific Antigen/ Epithelial cell adhesion molecule Monoclonal Antibody (MOC31) positivity, indicating that the tumor may influence the microenvironment of the tumor in the vicinity. Furthermore, the next-generation sequencing studies performed on the specimen with plasmacytoma and chronic lymphocytic lymphoma demonstrated BReast CAncer gene (BRCA2) and Tumor Necrosis Factor Alpha Induced Protein 3 (TNFAIP3) as a disease associated variants suggestive of risk for multiple tumors including collision tumors. Our reports highlight the unique collision tumors involving plasmacytoma, which have never been reported previously, as well as provide necessary insights about the underline genetic aberrations and tumor heterogeneity through sequencing studies and allow clonality assessment for subsequent tumors.

Keywords: BRCA2, collision tumor, chronic lymphocytic leukemia, plasmacytoma

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1281 Small Molecule Inhibitors of PD1-PDL1 Interaction

Authors: K. Żak, S. Przetocka, R. Kitel, K. Guzik, B. Musielak, S. Malicki, G. Dubin, T. A. Holak

Abstract:

Studies on tumor genesis revealed a number of factors that may potentially serve as molecular targets for immunotherapies. One of such promising targets are PD1 and PDL1 proteins. PD1 (Programmed cell death protein 1) is expressed by activated T cells and plays a critical role in modulation of the host's immune response. One of the PD1 ligands -PDL1- is expressed by macrophages, monocytes and cancer cells which exploit it to avoid immune attack. The notion of the mechanisms used by cancer cells to block the immune system response was utilized in the development of therapies blocking PD1-PDL1 interaction. Up to date, human PD1-PDL1 complex has not been crystallized and structure of the mouse-human complex does not provide a complete view of the molecular basis of PD1-PDL1 interactions. The purpose of this study is to obtain crystal structure of the human PD1-PDL1 complex which shall allow rational design of small molecule inhibitors of the interaction. In addition, the study presents results of binding small-molecules to PD1 and fragment docking towards PD1 protein which will facilitate the design and development of small–molecule inhibitors of PD1-PDL1 interaction.

Keywords: PD1, PDL1, cancer, small molecule, drug discovery

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1280 Medical Radiation Exposure in a Cohort of Children Diagnosed with Solid Tumors: Single Institution Study 1985-2015

Authors: Robin L. Rohrer

Abstract:

Introduction: Pre-natal or early childhood exposure to the medical radiation used in diagnosis or treatment is an identified risk for childhood cancers but can be difficult to document. The author developed a family questionnaire/interview form to identify possible exposures. Aims: This retrospective study examines pre-natal and early childhood medical radiation exposure in a cohort of children diagnosed with a solid tumor including brain tumors from 1985-2015 at the Children’s Hospital of Pittsburgh (CHP). The hospital is a tri-state regional referral center which treats about 150-180 new cases of cancer in children per year. About 70% are diagnosed with a solid tumor. Methods: Each consented family so far (approximately 50% of the cohort) has been interviewed in person or by the phone call. Medical staff and psycho- social staff referred patient families for the interview with the author. Results: Among the families interviewed to date at least one medical radiation exposure has been identified (pre-conception, pre-natal or early childhood) in over 70% of diagnosed children. These exposures have included pre-conception sinus or chest CT or X-ray in either parent, sinus CT or X-ray in the mother or diagnostic radiation of chest or abdomen in children. Conclusions: Exposures to medical radiation for a child later diagnosed with cancer may occur at several critical junctures. These exposures may well contribute to a ‘perfect storm’ in the still elusive causes of childhood cancer. The author plans to expand the study from 1975 to present to hopefully further document these junctures.

Keywords: pediatric, solid tumors, medical radiation, cancer

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1279 CD133 and CD44 - Stem Cell Markers for Prediction of Clinically Aggressive Form of Colorectal Cancer

Authors: Ognen Kostovski, Svetozar Antovic, Rubens Jovanovic, Irena Kostovska, Nikola Jankulovski

Abstract:

Introduction:Colorectal carcinoma (CRC) is one of the most common malignancies in the world. The cancer stem cell (CSC) markers are associated with aggressive cancer types and poor prognosis. The aim of study was to determine whether the expression of colorectal cancer stem cell markers CD133 and CD44 could be significant in prediction of clinically aggressive form of CRC. Materials and methods: Our study included ninety patients (n=90) with CRC. Patients were divided into two subgroups: with metatstatic CRC and non-metastatic CRC. Tumor samples were analyzed with standard histopathological methods, than was performed immunohistochemical analysis with monoclonal antibodies against CD133 and CD44 stem cell markers. Results: High coexpression of CD133 and CD44 was observed in 71.4% of patients with metastatic disease, compared to 37.9% in patients without metastases. Discordant expression of both markers was found in 8% of the subgroup with metastatic CRC, and in 13.4% of the subgroup without metastatic CRC. Statistical analyses showed a significant association of increased expression of CD133 and CD44 with the disease stage, T - category and N - nodal status. With multiple regression analysis the stage of disease was designate as a factor with the greatest statistically significant influence on expression of CD133 (p <0.0001) and CD44 (p <0.0001). Conclusion: Our results suggest that the coexpression of CD133 and CD44 have an important role in prediction of clinically aggressive form of CRC. Both stem cell markers can be routinely implemented in standard pathohistological diagnostics and can be useful markers for pre-therapeutic oncology screening.

Keywords: colorectal carcinoma, stem cells, CD133+, CD44+

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1278 Incidence of Vulval, Vaginal and Cervical Disease in Rapid Access Clinic in a London Tertiary Hospital Setting

Authors: Kieren Wilson, Gulnaz Majeed

Abstract:

NHS constitution gives rights to the patient with suspected cancer to be seen by a cancer specialist within 2 weeks of referral. Guys and St Thomas Hospital (GSTT) is one of the largest cancer centres in London. NICE guidelines have provided guidance for health professionals to refer patients appropriately to RAC. In GSTT suspected gynae cancer referrals are mostly by NHS e-Referral Service with some fax, emails as well as paper referrals. The objective of this study was to evaluate compliance with 2-week referral pathway with emphasis on one stop diagnostic service with supporting efficient pathways. A prospective evaluation over 3 months (1 Jan 2017 to 31 Mar 2017) was undertaken. There were 26 clinics, 761 patients were booked in the clinics with a DNA rate of 13% (n=101) hence 606 patients were seen. Majority of referrals were for post menopausal bleeding (PMB) 25% (n=194) followed by cervical, vaginal, vulval reasons 23% (n=179) (abnormal cytology excluded as patients directly referred to colposcopy unit in GSTT), ovarian 7% (n=54) and endometrial 5% (n=41). Women with new or previous established diagnosis of cancer were 24, cervical (n=17), vulva (n=6) and vagina (n=1). Multifocal preinvasive disease vulva (VIN), vagina (VAIN) and cervix (CIN) was confirmed in twenty-six patients 4% (high prevalence in HIV patients). Majority of cervical referrals: PCB (n=14), cervical erosion (n=7), polyps (n=9) and cervical cyst were benign. However, two women with PMB had cervical cancer. Only 2 out of 13 referrals with vaginal concerns had VAIN. One case with non-cervical glandular cytology was confirmed to have endometrial cancer. One stop service based on the diagnostic support of ultrasound, colposcopy and hysteroscopy was achieved in 54% (n=359). Patients were discharged to GP, benign gynaecology, endometriosis, combined vulval/dermatology clinic or gynae oncology. 33% (n=202) required a second visit, 12% (n=70) third visit, 3% (n=19) fourth visit, 1% (n=4) fifth visit and 1% (n=6) sixth visit. Main reasons for follow ups were the unavailability of diagnostic slots, patient choice, need for interpreters, the discussion following gynae MDM review for triage to benign gynae, delay in availability of diagnostic results like histology/MRI/CT. Recommendations following this study are multi disciplinary review of pathways with the availability of additional diagnostic procedure slots to aim for one stop service. Furthermore, establishment of virtual and telephone consultations to reduce follow ups.

Keywords: multifocal disease, post menopausal bleeding, preinvasive disease, rapid access clinic

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1277 Induction of Cytotoxicity and Apoptosis in Ovarian Cancer Cell Line (CAOV-3) by an Isoquinoline Alkaloid Isolated from Enicosanthellum pulchrum (King) Heusden

Authors: Noraziah Nordin, Najihah Mohd Hashim, Nazia Abdul Majid, Mashitoh Abdul Rahman, Hamed Karimian, Hapipah Mohd Ali

Abstract:

Enicosanthellum pulchrum belongs to family Annonaceae is also known as family of 'mempisang' in Malaysia. Liriodenine was isolated by prep-HPLC method. This method was first technique used for the isolation of this compound. The structure of the liriodenine was elucidated by 1D and 2D spectroscopy techniques. Liriodenine was tested on ovarian cancer cells line (CAOV-3) for MTT, AO/PI and cytotoxicity 3 assays. The MTT assay was performed to determine the cytotoxicity effect of lirodenine on CAOV-3 cells. The morphological changes on CAOV-3 cells were observed by AO/PI assay for the early and late stage of apoptosis, as well as necrosis. Meanwhile, the measurement of cell loss, nuclear morphology, DNA content, cell membrane permeability, mitochondrial membrane potential changes and cytochrome c release from mitochondria were detected through cytotoxicity 3 assay. The IC50 results showed liriodenine inhibits the growth of CAOV-3 cells after 24 h of treatment at 10.25 ± 1.06 µg/mL. After 48 and 72 h of treatments, the IC50 values were decreased to 7.65 ± 0:07 and 6.35 ± 1.62 µg/mL, respectively. The morphology changes can be seen on CAOV-3 with a production of cell membrane blebbing, cromatin condensation and apoptotic bodies with increasing time of treatment from 24 to 72 h. Evaluation of cytotoxicity 3 on CAOV-3 cells after treated with liriodenine, resulting loss of mitochondrial membrane potential and release of cytochrome c from mitochondria. The results demonstrated the capability of liriodenine as a promising anticancer agent, particularly on human ovarian cancer.

Keywords: Enicosanthellum pulchrum, ovarian cancer, apoptosis, cytotoxicity

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1276 Comprehensive Analysis of RNA m5C Regulator ALYREF as a Suppressive Factor of Anti-tumor Immune and a Potential Tumor Prognostic Marker in Pan-Cancer

Authors: Yujie Yuan, Yiyang Fan, Hong Fan

Abstract:

Objective: The RNA methylation recognition protein Aly/REF export factor (ALYREF) is considered one type of “reader” protein acting as a recognition protein of m5C, has been reported involved in several biological progresses including cancer initiation and progression. 5-methylcytosine (m5C) is a conserved and prevalent RNA modification in all species, as accumulating evidence suggests its role in the promotion of tumorigenesis. It has been claimed that ALYREF mediates nuclear export of mRNA with m5C modification and regulates biological effects of cancer cells. However, the systematical regulatory pathways of ALYREF in cancer tissues have not been clarified, yet. Methods: The expression level of ALYREF in pan-cancer and their normal tissues was compared through the data acquired from The Cancer Genome Atlas (TCGA). The University of Alabama at Birmingham Cancer data analysis Portal UALCAN was used to analyze the relationship between ALYREF and clinical pathological features. The relationship between the expression level of ALYREF and prognosis of pan-cancer, and the correlation genes of ALYREF were figured out by using Gene Expression Correlation Analysis database GEPIA. Immune related genes were obtained from TISIDB (an integrated repository portal for tumor-immune system interactions). Immune-related research was conducted by using Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) and TIMER. Results: Based on the data acquired from TCGA, ALYREF has an obviously higher-level expression in various types of cancers compared with relevant normal tissues excluding thyroid carcinoma and kidney chromophobe. The immunohistochemical images on The Human Protein Atlas showed that ALYREF can be detected in cytoplasm, membrane, but mainly located in nuclear. In addition, a higher expression level of ALYREF in tumor tissue generates a poor prognosis in majority of cancers. According to the above results, cancers with a higher expression level of ALYREF compared with normal tissues and a significant correlation between ALYREF and prognosis were selected for further analysis. By using TISIDB, we found that portion of ALYREF co-expression genes (such as BIRC5, H2AFZ, CCDC137, TK1, and PPM1G) with high Pearson correlation coefficient (PCC) were involved in anti-tumor immunity or affect resistance or sensitivity to T cell-mediated killing. Furthermore, based on the results acquired from GEPIA, there was significant correlation between ALYREF and PD-L1. It was exposed that there is a negative correlation between the expression level of ALYREF and ESTIMATE score. Conclusion: The present study indicated that ALYREF plays a vital and universal role in cancer initiation and progression of pan-cancer through regulating mitotic progression, DNA synthesis and metabolic process, and RNA processing. The correlation between ALYREF and PD-L1 implied ALYREF may affect the therapeutic effect of immunotherapy of tumor. More evidence revealed that ALYREF may play an important role in tumor immunomodulation. The correlation between ALYREF and immune cell infiltration level indicated that ALYREF can be a potential therapeutic target. Exploring the regulatory mechanism of ALYREF in tumor tissues may expose the reason for poor efficacy of immunotherapy and offer more directions of tumor treatment.

Keywords: ALYREF, pan-cancer, immunotherapy, PD-L1

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1275 MAGE-A3 and PRAME Gene Expression and EGFR Mutation Status in Non-Small-Cell Lung Cancer

Authors: Renata Checiches, Thierry Coche, Nicolas F. Delahaye, Albert Linder, Fernando Ulloa Montoya, Olivier Gruselle, Karen Langfeld, An de Creus, Bart Spiessens, Vincent G. Brichard, Jamila Louahed, Frédéric F. Lehmann

Abstract:

Background: The RNA-expression levels of cancer-testis antigens MAGE A3 and PRAME were determined in resected tissue from patients with primary non-small-cell lung cancer (NSCLC) and related to clinical outcome. EGFR, KRAS and BRAF mutation status was determined in a subset to investigate associations with MAGE A3 and PRAME expression. Methods: We conducted a single-centre, uncontrolled, retrospective study of 1260 tissue-bank samples from stage IA-III resected NSCLC. The prognostic value of antigen expression (qRT-PCR) was determined by hazard-ratio and Kaplan-Meier curves. Results: Thirty-seven percent (314/844) of tumours expressed MAGE-A3, 66% (723/1092) expressed PRAME and 31% (239/839) expressed both. Respective frequencies in squamous-cell tumours and adenocarcinomas were 43%/30% for MAGE A3 and 80%/44% for PRAME. No correlation with stage, tumour size or patient age was found. Overall, no prognostic value was identified for either antigen. A trend to poorer overall survival was associated with MAGE-A3 in stage IIIB and with PRAME in stage IB. EGFR and KRAS mutations were found in 10.1% (28/311) and 33.8% (97/311) of tumours, respectively. EGFR (but not KRAS) mutation status was negatively associated with PRAME expression. Conclusion: No clear prognostic value for either PRAME or MAGE A3 was observed in the overall population, although some observed trends may warrant further investigation.

Keywords: MAGE A3, PRAME, cancer-testis gene, NSCLC, survival, EGFR

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1274 A Novel Bio-ceramic Using Hyperthermia for Bone Cancer Therapy, Ferro-substituted Silicate Calcium Materials

Authors: hassan gheisari

Abstract:

Ferro silicate calcium nano particles are prepared through the sol-gel method using polyvinyl alcohol (PVA) as a chelating agent. The powder, as prepared, is annealed at three different temperatures (900 ºC, 1000 ºC, and 1100 ºC) for 3 h. The XRD patterns of the samples indicate broad peaks, and the full width at half maximum decreased with increasing annealing temperature. FTIR spectra of the samples confirm the presence of metal - oxygen complexes within the structure. The average particle size obtained from PSA curve demonstrates ultrafine particles. SEM micrographs indicate the particles synthesized have spherical morphology. The saturation magnetization (Ms) and remnant magnetization (Mr) of the samples show dependence on particle size and crystallinity of the samples. The highest saturation magnetization is achieved for the sample annealed at 1100 ºC having maximum average particle size. The high saturation magnetization of the samples suggests the present method is suitable for obtaining nano particles magnetic ferro bioceramic, which is desirable for practical applications such as hyperthermia bone cancer therapy.

Keywords: hyperthermia, bone cancer, bio ceramic; magnetic materials; sol– gel, silicate calcium

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1273 Ferro-Substituted Silicate Calcium Materials, a Novel Bio-Ceramic Using Hyperthermia for Bone Cancer Therapy

Authors: Hassan Gheisari

Abstract:

Ferro silicate calcium nano particles are prepared through the sol-gel method using polyvinyl alcohol (PVA) as a chelating agent. The powder as prepared is annealed at three different temperatures (900 ºC, 1000 ºC and 1100 ºC) for 3 h. The XRD patterns of the samples indicate broad peaks and the full width at half maximum decreased with increasing annealing temperature. FTIR spectra of the samples confirm the presence of metal - oxygen complexes within the structure. The average particle size obtained from PSA curve demonstrates ultrafine particles. SEM micrographs indicate the particles synthesized have spherical morphology. The saturation magnetization (Ms) and remnant magnetization (Mr) of the samples show dependence on particle size and crystallinity of the samples. The highest saturation magnetization is achieved for the sample annealed at 1100 ºC having maximum average particle size. The high saturation magnetization of the samples suggests the present method is suitable for obtaining nano particles magnetic ferro bioceramic which is desirable for practical applications such as hyperthermia bone cancer therapy.

Keywords: hyperthermia, bone cancer, bio ceramic, magnetic materials, sol– gel, silicate calcium

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1272 Effect of Radiotherapy/Chemotherapy Protocol on the Gut Microbiome in Pediatric Cancer Patients

Authors: Nourhan G. Sahly, Ahmed Moustafa, Mohamed S. Zaghloul, Tamer Z. Salem

Abstract:

The gut microbiome plays important roles in the human body that includes but not limited to digestion, immunity, homeostasis and response to some drugs such as chemotherapy and immunotherapy. Its role has also been linked to radiotherapy and associated gastrointestinal injuries, where the microbial dysbiosis could be the driving force for dose determination or the complete suspension of the treatment protocol. Linking the gut microbiota alterations to different cancer treatment protocols is not easy especially in humans. However, enormous effort was exerted to understand this complex relationship. In the current study, we described the gut microbiota dysbiosis in pediatric sarcoma patients, in the pelvic region, with regards to radiotherapy and antibiotics. Fecal samples were collected as a source of microbial DNA for which the gene encoding for V3-V5 regions of 16S rRNA was sequenced. Two of the three patients understudy had experienced an increase in alpha diversity post exposure to 50.4 Gy. Although phylum Firmicutes overall relative abundance has generally decreased, six of its taxa increased in all patients. Our results may indicate the possibility of radiosensitivity or enrichment of the antibiotic resistance of the elevated taxa. Further studies are needed to describe the extent of radiosensitivity with regards to antibiotic resistance.

Keywords: combined radiotherapy and chemotherapy, gut microbiome, pediatric cancer, radiosensitivity

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1271 Survey of Indoor Radon/Thoron Concentrations in High Lung Cancer Incidence Area in India

Authors: Zoliana Bawitlung, P. C. Rohmingliana, L. Z. Chhangte, Remlal Siama, Hming Chungnunga, Vanram Lawma, L. Hnamte, B. K. Sahoo, B. K. Sapra, J. Malsawma

Abstract:

Mizoram state has the highest lung cancer incidence rate in India due to its high-level consumption of tobacco and its products which is supplemented by the food habits. While smoking is mainly responsible for this incidence, the effect of inhalation of indoor radon gas cannot be discarded as the hazardous nature of this radioactive gas and its progenies on human population have been well-established worldwide where the radiation damage to bronchial cells eventually can be the second leading cause of lung cancer next to smoking. It is also known that the effect of radiation, however, small may be the concentration, cannot be neglected as they can bring about the risk of cancer incidence. Hence, estimation of indoor radon concentration is important to give a useful reference against radiation effects as well as establishing its safety measures and to create a baseline for further case-control studies. The indoor radon/thoron concentrations in Mizoram had been measured in 41 dwellings selected on the basis of spot gamma background radiation and construction type of the houses during 2015-2016. The dwellings were monitored for one year, in 4 months cycles to indicate seasonal variations, for the indoor concentration of radon gas and its progenies, outdoor gamma dose, and indoor gamma dose respectively. A time-integrated method using Solid State Nuclear Track Detector (SSNTD) based single entry pin-hole dosimeters were used for measurement of indoor Radon/Thoron concentration. Gamma dose measurements for indoor as well as outdoor were carried out using Geiger Muller survey meters. Seasonal variation of indoor radon/ thoron concentration was monitored. The results show that the annual average radon concentrations varied from 54.07 – 144.72 Bq/m³ with an average of 90.20 Bq/m³ and the annual average thoron concentration varied from 17.39 – 54.19 Bq/m³ with an average of 35.91 Bq/m³ which are below the permissible limit. The spot survey of gamma background radiation level varies between 9 to 24 µR/h inside and outside the dwellings throughout Mizoram which are all within acceptable limits. From the above results, there is no direct indication that radon/thoron is responsible for the high lung cancer incidence in the area. In order to find epidemiological evidence of natural radiations to high cancer incidence in the area, one may need to conduct a case-control study which is beyond this scope. However, the derived data of measurement will provide baseline data for further studies.

Keywords: background gamma radiation, indoor radon/thoron, lung cancer, seasonal variation

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1270 A Left Testicular Cancer with Multiple Metastases Nursing Experience

Authors: Syue-Wen Lin

Abstract:

Objective:This article reviews the care experience of a 40-year-old male patient who underwent a thoracoscopic right lower lobectomy following a COVID-19 infection. His complex medical history included multiple metastases (lungs, liver, spleen, and left kidney) and lung damage from COVID-19, which complicated the weaning process from mechanical ventilation. The care involved managing cancer treatment, postoperative pain, wound care, and palliative care. Methods:Nursing care was provided from August 16 to August 17, 2024. Challenges included difficulty with sputum clearance, which exacerbated the patient's anxiety and fear of reintubation. Pain management strategies combined analgesic drugs, non-drug methods, essential oil massages with family members, and playing the patient’s favorite music to reduce pain and anxiety. Progressive rehabilitation began with stabilizing vital signs, followed by assistance with sitting on the edge of the bed and walking within the ward. Strict sterile procedures and advanced wound care technology were used for daily dressing changes, with meticulous documentation of wound conditions and appropriate dressing selection. Holistic cancer care and palliative measures were integrated to address the patient’s physical and psychological needs. Results:The interdisciplinary care team developed a comprehensive plan addressing both physical and psychological aspects. Respiratory therapy, lung expansion exercises, and a high-frequency chest wall oscillation vest facilitated sputum expulsion and assisted in weaning from mechanical ventilation. The integration of cancer care, pain management, wound care, and palliative care led to improved quality of life and recovery. The collaborative approach between nursing staff and family ensured that the patient received compassionate and effective care. Conclusion: The complex interplay of emergency surgery, COVID-19, and advanced cancer required a multifaceted care strategy. The care team’s approach, combining critical care with tailored cancer and palliative care, effectively improved the patient’s quality of life and facilitated recovery. The comprehensive care plan, developed with family collaboration, provided both high-quality medical care and compassionate support for the terminally ill patient.

Keywords: multiple metastases, testicular cancer, palliative care, nursing experience

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1269 Physicians’ Knowledge and Perception of Gene Profiling in Malaysia: A Pilot Study

Authors: Farahnaz Amini, Woo Yun Kin, Lazwani Kolandaiveloo

Abstract:

Availability of different genetic tests after completion of Human Genome Project increases the physicians’ responsibility to keep themselves update on the potential implementation of these genetic tests in their daily practice. However, due to numbers of barriers, still many of physicians are not either aware of these tests or are not willing to offer or refer their patients for genetic tests. This study was conducted an anonymous, cross-sectional, mailed-based survey to develop a primary data of Malaysian physicians’ level of knowledge and perception of gene profiling. Questionnaire had 29 questions. Total scores on selected questions were used to assess the level of knowledge. The highest possible score was 11. Descriptive statistics, one way ANOVA and chi-squared test was used for statistical analysis. Sixty three completed questionnaires was returned by 27 general practitioners (GPs) and 36 medical specialists. Responders’ age range from 24 to 55 years old (mean 30.2 ± 6.4). About 40% of the participants rated themselves as having poor level of knowledge in genetics in general whilst 60% believed that they have fair level of knowledge. However, almost half (46%) of the respondents felt that they were not knowledgeable about available genetic tests. A majority (94%) of the responders were not aware of any lab or company which is offering gene profiling services in Malaysia. Only 4% of participants were aware of using gene profiling for detection of dosage of some drugs. Respondents perceived greater utility of gene profiling for breast cancer (38%) compared to the colorectal familial cancer (3%). The score of knowledge ranged from 2 to 8 (mean 4.38 ± 1.67). Non-significant differences between score of knowledge of GPs and specialists were observed, with score of 4.19 and 4.58 respectively. There was no significant association between any demographic factors and level of knowledge. However, those who graduated between years 2001 to 2005 had higher level of knowledge. Overall, 83% of participants showed relatively high level of perception on value of gene profiling to detect patient’s risk of disease. However, low perception was observed for both statements of using gene profiling for general population in order to alter their lifestyle (25%) as well as having the full sequence of a patient genome for the purpose of determining a patient’s best match for treatment (18%). The lack of clinical guidelines, limited provider knowledge and awareness, lack of time and resources to educate patients, lack of evidence-based clinical information and cost of tests were the most barriers of ordering gene profiling mentioned by physicians. In conclusion Malaysian physicians who participate in this study had mediocre level of knowledge and awareness in gene profiling. The low exposure to the genetic questions and problems might be a key predictor of lack of awareness and knowledge on available genetic tests. Educational and training workshop might be useful in helping Malaysian physicians incorporate genetic profiling into practice for eligible patients.

Keywords: gene profiling, knowledge, Malaysia, physician

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1268 In silico Repopulation Model of Various Tumour Cells during Treatment Breaks in Head and Neck Cancer Radiotherapy

Authors: Loredana G. Marcu, David Marcu, Sanda M. Filip

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Advanced head and neck cancers are aggressive tumours, which require aggressive treatment. Treatment efficiency is often hindered by cancer cell repopulation during radiotherapy, which is due to various mechanisms triggered by the loss of tumour cells and involves both stem and differentiated cells. The aim of the current paper is to present in silico simulations of radiotherapy schedules on a virtual head and neck tumour grown with biologically realistic kinetic parameters. Using the linear quadratic formalism of cell survival after radiotherapy, altered fractionation schedules employing various treatment breaks for normal tissue recovery are simulated and repopulation mechanism implemented in order to evaluate the impact of various cancer cell contribution on tumour behaviour during irradiation. The model has shown that the timing of treatment breaks is an important factor influencing tumour control in rapidly proliferating tissues such as squamous cell carcinomas of the head and neck. Furthermore, not only stem cells but also differentiated cells, via the mechanism of abortive division, can contribute to malignant cell repopulation during treatment.

Keywords: radiation, tumour repopulation, squamous cell carcinoma, stem cell

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1267 Evaluation of the Cytotoxicity and Cellular Uptake of a Cyclodextrin-Based Drug Delivery System for Cancer Therapy

Authors: Caroline Mendes, Mary McNamara, Orla Howe

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Drug delivery systems are proposed for use in cancer treatment to specifically target cancer cells and deliver a therapeutic dose without affecting normal cells. For that purpose, the use of folate receptors (FR) can be considered a key strategy, since they are commonly over-expressed in cancer cells. In this study, cyclodextrins (CD) have being used as vehicles to target FR and deliver the chemotherapeutic drug, methotrexate (MTX). CDs have the ability to form inclusion complexes, in which molecules of suitable dimensions are included within their cavities. Here, β-CD has been modified using folic acid so as to specifically target the FR. Thus, this drug delivery system consists of β-CD, folic acid and MTX (CDEnFA:MTX). Cellular uptake of folic acid is mediated with high affinity by folate receptors while the cellular uptake of antifolates, such as MTX, is mediated with high affinity by the reduced folate carriers (RFCs). This study addresses the gene (mRNA) and protein expression levels of FRs and RFCs in the cancer cell lines CaCo-2, SKOV-3, HeLa, MCF-7, A549 and the normal cell line BEAS-2B, quantified by real-time polymerase chain reaction (real-time PCR) and flow cytometry, respectively. From that, four cell lines with different levels of FRs, were chosen for cytotoxicity assays of MTX and CDEnFA:MTX using the MTT assay. Real-time PCR and flow cytometry data demonstrated that all cell lines ubiquitously express moderate levels of RFC. These experiments have also shown that levels of FR protein in CaCo-2 cells are high, while levels in SKOV-3, HeLa and MCF-7 cells are moderate. A549 and BEAS-2B cells express low levels of FR protein. FRs are highly expressed in all the cancer cell lines analysed when compared to the normal cell line BEAS-2B. The cell lines CaCo-2, MCF-7, A549 and BEAS-2B were used in the cell viability assays. 48 hours treatment with the free drug and the complex resulted in IC50 values of 93.9 µM ± 15.2 and 56.0 µM ± 4.0 for CaCo-2 for free MTX and CDEnFA:MTX respectively, 118.2 µM ± 16.8 and 97.8 µM ± 12.3 for MCF-7, 36.4 µM ± 6.9 and 75.0 µM ± 10.5 for A549 and 132.6 µM ± 16.1 and 288.1 µM ± 26.3 for BEAS-2B. These results demonstrate that free MTX is more toxic towards cell lines expressing low levels of FR, such as the BEAS-2B. More importantly, these results demonstrate that the inclusion complex CDEnFA:MTX showed greater cytotoxicity than the free drug towards the high FR expressing CaCo-2 cells, indicating that it has potential to target this receptor, enhancing the specificity and the efficiency of the drug. The use of cell imaging by confocal microscopy has allowed visualisation of FR targeting in cancer cells, as well as the identification of the interlisation pathway of the drug. Hence, the cellular uptake and internalisation process of this drug delivery system is being addressed.

Keywords: cancer treatment, cyclodextrins, drug delivery, folate receptors, reduced folate carriers

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1266 Pegylated Liposomes of Trans Resveratrol, an Anticancer Agent, for Enhancing Therapeutic Efficacy and Long Circulation

Authors: M. R. Vijayakumar, Sanjay Kumar Singh, Lakshmi, Hithesh Dewangan, Sanjay Singh

Abstract:

Trans resveratrol (RES) is a natural molecule proved for cancer preventive and therapeutic activities devoid of any potential side effects. However, the therapeutic application of RES in disease management is limited because of its rapid elimination from blood circulation thereby low biological half life in mammals. Therefore, the main objective of this study is to enhance the circulation as well as therapeutic efficacy using PEGylated liposomes. D-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) is applied as steric surface decorating agent to prepare RES liposomes by thin film hydration method. The prepared nanoparticles were evaluated by various state of the art techniques such as dynamic light scattering (DLS) technique for particle size and zeta potential, TEM for shape, differential scanning calorimetry (DSC) for interaction analysis and XRD for crystalline changes of drug. Encapsulation efficiency and invitro drug release were determined by dialysis bag method. Cancer cell viability studies were performed by MTT assay, respectively. Pharmacokinetic studies were performed in sprague dawley rats. The prepared liposomes were found to be spherical in shape. Particle size and zeta potential of prepared formulations varied from 64.5±3.16 to 262.3±7.45 nm and -2.1 to 1.76 mV, respectively. DSC study revealed absence of potential interaction. XRD study revealed presence of amorphous form in liposomes. Entrapment efficiency was found to be 87.45±2.14 % and the drug release was found to be controlled up to 24 hours. Minimized MEC in MTT assay and tremendous enhancement in circulation time of RES PEGylated liposomes than its pristine form revealed that the stearic stabilized PEGylated liposomes can be an alternative tool to commercialize this molecule for chemopreventive and therapeutic applications in cancer.

Keywords: trans resveratrol, cancer nanotechnology, long circulating liposomes, bioavailability enhancement, liposomes for cancer therapy, PEGylated liposomes

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1265 A Study on the Application of Machine Learning and Deep Learning Techniques for Skin Cancer Detection

Authors: Hritwik Ghosh, Irfan Sadiq Rahat, Sachi Nandan Mohanty, J. V. R. Ravindra

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In the rapidly evolving landscape of medical diagnostics, the early detection and accurate classification of skin cancer remain paramount for effective treatment outcomes. This research delves into the transformative potential of Artificial Intelligence (AI), specifically Deep Learning (DL), as a tool for discerning and categorizing various skin conditions. Utilizing a diverse dataset of 3,000 images representing nine distinct skin conditions, we confront the inherent challenge of class imbalance. This imbalance, where conditions like melanomas are over-represented, is addressed by incorporating class weights during the model training phase, ensuring an equitable representation of all conditions in the learning process. Our pioneering approach introduces a hybrid model, amalgamating the strengths of two renowned Convolutional Neural Networks (CNNs), VGG16 and ResNet50. These networks, pre-trained on the ImageNet dataset, are adept at extracting intricate features from images. By synergizing these models, our research aims to capture a holistic set of features, thereby bolstering classification performance. Preliminary findings underscore the hybrid model's superiority over individual models, showcasing its prowess in feature extraction and classification. Moreover, the research emphasizes the significance of rigorous data pre-processing, including image resizing, color normalization, and segmentation, in ensuring data quality and model reliability. In essence, this study illuminates the promising role of AI and DL in revolutionizing skin cancer diagnostics, offering insights into its potential applications in broader medical domains.

Keywords: artificial intelligence, machine learning, deep learning, skin cancer, dermatology, convolutional neural networks, image classification, computer vision, healthcare technology, cancer detection, medical imaging

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1264 Association of miRNA146a rs2910164 Polymorphism and Helicobacter pylori Infection in Colorectal Cancer

Authors: Zahra Solgi, Hossein Rassi

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Colorectal cancer (CRC) is a multi-step disease, and chronic gastric infection with H. pylori could play a role in one or more of the steps in this pathogenic process. Polymorphisms in several miRNAs are considered to increase the risk for the development of CRC by controlling proliferation, apoptosis and H. pylori pathogenesis. Therefore, the aim of this study was to investigate miRNA146a rs2910164 polymorphism and Helicobacter pylori infection in CRC. A total of 65 patients with CRC were divided into 2 groups: 28 patients < 50 years of age and 37 patients ≥ 50 years of age. DNA was extracted from all samples by a standard method and H. pylori cagA and miRNA146a rs2910164 genotypes were determined by PCR method. The results show that there was no significant difference in the frequency of H. pylori cagA gene between the two groups but there was a significant difference in the distribution of rs2910164 genotypes in patients < 50 years of age with the p-value of 0.05 and odds ratio equal to 2.69. On other hand, patients < 50 years of age with genotype CC of miRNA146a showed a significant difference in CRC risk. Furthermore, there was a significant correlation between rs2910164 CC genotype with Helicobacter pylori infection in patients < 50 years of age. The present study suggests that the CC genotype of miRNA146a in combination with H. pylori infection can be effective as risk factors and molecular markers for early diagnosis and treatment of CRC.

Keywords: colorectal cancer, Helicobacter pylori, miRNA146a, rs2910164 polymorphism

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1263 Evaluating the Effectiveness of Combined Psychiatric and Psychotherapeutic Care versus Psychotherapy Alone in the Treatment of Depression and Anxiety in Cancer Patients

Authors: Nathen A. Spitz, Dennis Martin Kivlighan III, Arwa Aburizik

Abstract:

Background and Purpose: Presently, there is a paucity of naturalistic studies that directly compare the effectiveness of psychotherapy versus concurrent psychotherapy and psychiatric care for the treatment of depression and anxiety in cancer patients. Informed by previous clinical trials examining the efficacy of concurrent approaches, this study sought to test the hypothesis that a combined approach would result in the greatest reduction of depression and anxiety symptoms. Methods: Data for this study consisted of 433 adult cancer patients, with 252 receiving only psychotherapy and 181 receiving concurrent psychotherapy and psychiatric care at the University of Iowa Hospitals and Clinics. Longitudinal PHQ9 and GAD7 data were analyzed between both groups using latent growth curve analyses. Results: After controlling for treatment length and provider effects, results indicated that concurrent care was more effective than psychotherapy alone for depressive symptoms (γ₁₂ = -0.12, p = .037). Specifically, the simple slope for concurrent care was -0.25 (p = .022), and the simple slope for psychotherapy alone was -0.13 (p = .006), suggesting that patients receiving concurrent care experienced a greater reduction in depressive symptoms compared to patients receiving psychotherapy alone. In contrast, there were no significant differences between psychotherapy alone and concurrent psychotherapy and psychiatric care in the reduction of anxious symptoms. Conclusions: Overall, as both psychotherapy and psychiatric care may address unique aspects of mental health conditions, in addition to potentially providing synergetic support to each other, a combinatorial approach to mental healthcare for cancer patients may improve outcomes.

Keywords: psychiatry, psychology, psycho-oncology, combined care, psychotherapy, behavioral psychology

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1262 Fuzzy Optimization for Identifying Anticancer Targets in Genome-Scale Metabolic Models of Colon Cancer

Authors: Feng-Sheng Wang, Chao-Ting Cheng

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Developing a drug from conception to launch is costly and time-consuming. Computer-aided methods can reduce research costs and accelerate the development process during the early drug discovery and development stages. This study developed a fuzzy multi-objective hierarchical optimization framework for identifying potential anticancer targets in a metabolic model. First, RNA-seq expression data of colorectal cancer samples and their healthy counterparts were used to reconstruct tissue-specific genome-scale metabolic models. The aim of the optimization framework was to identify anticancer targets that lead to cancer cell death and evaluate metabolic flux perturbations in normal cells that have been caused by cancer treatment. Four objectives were established in the optimization framework to evaluate the mortality of cancer cells for treatment and to minimize side effects causing toxicity-induced tumorigenesis on normal cells and smaller metabolic perturbations. Through fuzzy set theory, a multiobjective optimization problem was converted into a trilevel maximizing decision-making (MDM) problem. The applied nested hybrid differential evolution was applied to solve the trilevel MDM problem using two nutrient media to identify anticancer targets in the genome-scale metabolic model of colorectal cancer, respectively. Using Dulbecco’s Modified Eagle Medium (DMEM), the computational results reveal that the identified anticancer targets were mostly involved in cholesterol biosynthesis, pyrimidine and purine metabolisms, glycerophospholipid biosynthetic pathway and sphingolipid pathway. However, using Ham’s medium, the genes involved in cholesterol biosynthesis were unidentifiable. A comparison of the uptake reactions for the DMEM and Ham’s medium revealed that no cholesterol uptake reaction was included in DMEM. Two additional media, i.e., a cholesterol uptake reaction was included in DMEM and excluded in HAM, were respectively used to investigate the relationship of tumor cell growth with nutrient components and anticancer target genes. The genes involved in the cholesterol biosynthesis were also revealed to be determinable if a cholesterol uptake reaction was not induced when the cells were in the culture medium. However, the genes involved in cholesterol biosynthesis became unidentifiable if such a reaction was induced.

Keywords: Cancer metabolism, genome-scale metabolic model, constraint-based model, multilevel optimization, fuzzy optimization, hybrid differential evolution

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1261 Methodology for Diagnosing Architecture Improvements in a Cancer Hospital in Brasilia

Authors: Mariana Sabino, Janes Cleiton de Oliveira, Carlos Luna de Melo

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This paper presents a discussion about the importance and influence of the environment in the patient’s recovery process. Some users (employees and patients) were submitted to a questionnaire that helps to diagnoses the major problems of the hospital, specially related to comfort (aesthetic, thermal, acoustic, light, ergonomic), well-being, how does the flow of patients and employees works in the hospital and wayfinding as well. After a short literature review presenting the topic, the hospital will be characterized, showing photos, the projects available and describing the hospital as well (how many rooms, functions of each one, receptions, waiting rooms, between other things.), than the questionnaire will be applied to patients and to the employees. Lastly the results of the answers given will be analyzed in graphics, and it will help to identify which are the major improvements needed immediately. This paper has the intention to propose a methodology to diagnose architecture problems in a cancer hospital in Brasilia, Brazil, besides to open a space to hear the people that use the building to tell about their discomforts and perceptions of the environment, it also will give an opportunity to apply the possible improvements. It is important to tell that it will be considered if the hospital has a healing environment, and it will also be considered the ergonomic issues about comfort and the way the system of this particular hospital works in general.

Keywords: cancer hospital, comfort, diagnose, healing environment

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1260 Effects of Ethanolic Purslane Shoot and Seed Extracts on Doxorubicin-Induced Hepatotoxicity in Albino Rats

Authors: Osama M. Ahmed, Walaa G. Hozayen, Haidy Tamer Abo Sree

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Doxorubicin (DOX), an anthracycline antibiotic is a broad-spectrum antineoplastic agent, which is commonly used in the treatment of uterine, ovarian, breast and lung cancers, Hodgkin's disease and soft tissue sarcomas as well as in several other cancer types. The effect of doxorubicin (4 mg/kg b.w.week) without or with oral administration of ethanolic purslane (Portulaca oleracea) shoot (leaves and stems) extract (50 mg/kg b.w. day) or ethanolic purslane seeds extract (50 mg/kg b.w.day) co-treatments for 6 weeks was evaluated in adult male rats. Serum ALT, AST, ALP, GGT, total bilirubin, total protein, and albumin levels were assayed. Lipid peroxidation (indexed by MDA) and antioxidants like hepatic glutathine, glutathione transferase, peroxidase, SOD, and CAT were assessed. There was an increase in serum levels of ALT, AST, ALP, GGT and total bilirubin. In addition, hepatic glutathine, glutathione transferase, peroxidase, SOD, and CAT activities were decreased while lipid peroxidation in the liver was increased. Co-administration of ethanolic purslane and seed extracts successfully improved the adverse changes in the liver functions with an increase in antioxidants activities and reduction of lipid peroxidation. In conclusion, it can be supposed that dietary purslane extract supplementation may provide a cushion for a prolonged therapeutic option against DOX hepatopathy without harmful side effects. However, further clinical studies are required to assess the safety and efficacy of these extract in human beings.

Keywords: doxorubicin, purslane, hepatotoxicity, antioxidants

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1259 Literature Review of Empirical Studies on the Psychological Processes of End-of-Life Cancer Patients

Authors: Kimiyo Shimomai, Mihoko Harada

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This study is a literature review of the psychological reactions that occur in end-of-life cancer patients who are nearing death. It searched electronic databases and selected literature related to psychological studies of end-of-life patients. There was no limit on the search period, and the search was conducted until the second week of December 2021. The keywords were specified as “death and dying”, “terminal illness”, “end-of-life”, “palliative care”, “psycho-oncology” and “research”. These literatures referred to Holly (2017): Comprehensive Systematic Review for Advanced Practice Nursing, P268 Figure 10.3 to ensure quality. These literatures were selected with a dissertation score of 4 or 5. The review was conducted in two stages with reference to the procedure of George (2002). First, these references were searched for keywords in the database, and then relevant references were selected from the psychology and nursing studies of end-of-life patients. The number of literatures analyzed was 76 for overseas and 17 for domestic. As for the independent variables, "physical variable" was the most common in 36 literatures (66.7%), followed by "psychological variable" in 35 literatures (64.8%), "spiritual variable" in 21 literatures (38%), and "social variable" in 17 literatures. (31.5%), "Variables related to medical care / treatment" were 16 literatures (29.6%). To summarize the relationship between these independent variables and the dependent variable, when the dependent variable is "psychological variable", the independent variables are "psychological variable", "social variable", and "physical variable". Among the independent variables, the physical variables were the most common. The psychological responses that occur in end-stage cancer patients who are nearing death are mutually influenced by psychological, social, and physical variables. Therefore, it supported the "total pain" advocated by Cicely Saunders.

Keywords: cancer patient, end-of-life, literature review, psychological process

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