Common Form Of Cancer Research Articles

Applying Multimodal Mass Spectrometry to Image Tumors Undergoing Ferroptosis Following In Vivo Treatment with a Ferroptosis Inducer.

Epithelial ovarian cancer (EOC) is the most common form of ovarian cancer. The poor prognosis generally associated with this disease has led to the search for improved therapies such as ferroptosis-inducing agents. Ferroptosis is a form of regulated cell death that is dependent on iron and is characterized by lipid peroxidation. Precise mapping of lipids and iron within tumors exposed to ferroptosis-inducing agents may provide insight into processes of ferroptosis in vivo and ultimately assist in the optimal deployment of ferroptosis inducers in cancer therapy. In this work, we present a method for combining matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) with secondary ion mass spectrometry (SIMS) to analyze changes in spatial lipidomics and metal composition, respectively, in ovarian tumors following exposure to a ferroptosis inducer. Tumors were obtained by injecting human ovarian cancer tumor-initiating cells into mice, followed by treatment with the ferroptosis inducer erastin. SIMS imaging detected iron accumulation in the tumor tissue, and sequential MALDI-MS imaging of the same tissue section displayed two chemically distinct regions of lipids. One region was associated with the iron-rich area detected with SIMS, and the other region encompassed the remainder of the tissue section. Bulk lipidomics confirmed the lipid assignments putatively assigned from the MALDI-MS data. Overall, we demonstrate the ability of multimodal MSI to identify the spatial locations of iron and lipids in the same tissue section and associate these regions with clinical pathology.

Sperm mitochondria dysfunction in response to testicular cancer.

Testicular cancer is the most common form of cancer in young men of reproductive age and its incidence is increasing globally. With the currently successful treatment and 95% survival rate, there is a need for deeper understanding of testicular cancer-related infertility. Most patients with testicular cancer experience semen abnormalities prior to cancer therapy. However, the exact mechanism of the effect of testicular cancer on sperm anomalies is not known. Mitochondria are organelles that play a crucial role in both tumorigenesis and spermatogenesis and their malfunction may be an important factor resulting in sperm abnormalities in testicular cancer patients. Within the scope of this review, we will discuss current knowledge of testicular cancer-related alterations in the ATP production pathway, a possible pathophysiological switch from oxidative phosphorylation (OXPHOS) to glycolysis, as well as the role of oxidative stress promoting sperm dysfunction. In this regard, the review provides a summary of the impact of testicular cancer on sperm quality as a possible consequence of impaired mitochondrial function including the energy metabolic pathways that are known to be altered in the sperm of testicular cancer patients.

Breast cancer survival data prediction using machine learning model

Breast cancer is the most common form of cancer affecting women, exerting a significant impact on individuals, families, and societies globally. With its multifaceted nature, breast cancer research and awareness efforts have gained substantial momentum, leading to transformative breakthroughs in understanding its causes, diagnosis, treatment, and prevention. Survival analysis is a pivotal statistical tool in understanding the dynamic and often complex trajectory of breast cancer. As a disease that evolves, breast cancer research benefits immensely from survival analysis, which provides insights into patient outcomes, treatment efficacy, and the influence of various factors on survival. In this paper, Habermans Survival Dataset is used to analyze the data on breast cancer. The primary objective of this study is to establish the correlation between input and output variables, along with identifying significant features. The overarching aim of this research is to assess and compare the efficacy of various machine learning models in order to ascertain the optimal one.

PP33 The Cost-effectiveness Of Regorafenib In The Treatment Of Advanced Hepatocellular Carcinoma From A Canadian Perspective

IntroductionHepatocellular carcinoma (HCC) is the most common form of liver cancer and the fourth leading cause of cancer-related death globally. There are unmet needs for effective systematic therapy. The findings of the RESORCE trial highlighted the improvement in overall survival with regorafenib in advanced HCC patients progressing on sorafenib treatment. This study aimed to assess the cost-effectiveness of regorafenib compared with best supportive care (BSC) for advanced HCC from the Canadian healthcare system perspective.MethodsWe developed a Markov model based on four health states: live with adverse events, live without adverse events, progression, and dead. Health outcomes were measured using life-years (LYs), and quality-adjusted life-years (QALYs), and costs were presented in Canadian dollars (CAD). Clinical inputs were derived from the RESORCE trial. A 1.5 percent discount rate was applied to costs and outcomes. One-way and probabilistic sensitivity analyses were performed to assess the uncertainty in findings due to variability in parameters. TreeAge Pro software was used for model implementation.ResultsThe use of regorafenib results in a gain of 0.38 LYs and 0.25 QALYs as compared to BSC with a high incremental cost of CAD26,954 (USD22,313). The ICER for regorafenib compared with BSC was CAD105,850/QALY (USD87,624/QALY) in the base-case analysis. Further, probabilistic sensitivity analyses revealed regorafenib not to be cost-effective at a willingness-to-pay threshold of CAD50,000/QALY.ConclusionsRegorafenib was not found to be cost-effective in the treatment of advanced HCC because of the lower health benefits and higher incremental costs. Lowering the official price of regorafenib or use for only selected patients who can achieve maximum benefits would enhance its cost-effectiveness and treatment preference value.

Abstract B098: Adiposity measures and obesity-related cancer: A report from the Oklahoma Strong Heart Study and Strong Heart Family Study

Abstract Background: Obesity, defined as a body mass index (BMI) ≥30 kg/m2, disproportionately affects American Indian (AI) people and is increasingly implicated in the incidence of certain cancers. Indeed, while obesity-related cancers account for 43% of incident cancers among all Americans, they account for 51% of incident cancers among AI people. Emerging evidence indicates that body fat distribution (e.g., central vs. peripheral) is associated with cancer independent of BMI. AI adults have a higher prevalence of central adiposity than other populations, yet prospective measures of adiposity associated with increased risk of obesity-related cancer over time in AI people remain limited. Methods: We partnered with the Strong Heart Study/Strong Heart Family Study (SHS/SHFS) and the Oklahoma Central Cancer Registry to link study cohort records with cancer surveillance records from 1997-2019 to systematically classify cancer incidence among cohort participants. We evaluated baseline measures of adiposity, including waist circumference (females cutpoint at 88 cm, males cutpoint at 102 cm) waist-to-hip ratio (females cutpoint at 0.85, males cutpoint at 0.90), and percent body fat (females cutpoint at 35%, males cutpoint at 25%), by the presence of incident obesity-related cancer. We classified survival time as time from the baseline exam date to cancer diagnosis, death, or the end of the study period, whichever occurred first. Participants without a cancer event were censored. To compare survival time by each adiposity measure, we used the log-rank test and generated Kaplan-Meier curves. Results: We identified 140 participants with an obesity-related cancer that linked with a cancer registry record (n=1956 without cancer). The average age at the baseline SHS/SHFS exam was 54 years for those with cancer and 48 years for those without cancer. The average age at cancer diagnosis was 69 years. The most common forms of obesity-related cancer were colorectal (n=40, 29%) and post-menopausal female breast cancer (n=35, 25%). We observed a higher incidence of obesity-related cancer among those with high waist circumference (7.8% v. 4.3%), high waist-to-hip ratio (7.5% vs. 4.2%), and high percent body fat (7.4% v. 4.6%) compared with lower levels of these adiposity measures. We observed differences in time to cancer by waist circumference (p=0.004), waist-to-hip ratio (p=0.03), and percent body fat (p=0.03). Discussion: We observed significant differences in time to cancer diagnosis by multiple adiposity measures within the SHS/SHFS in Oklahoma. As a next step, we plan to link with the other SHS/SHFS sites in the Dakotas and Arizona. This study will provide a solid foundation upon which to base interventions to ameliorate risk factors for obesity-related factors in this underserved population. Citation Format: Amanda E. Janitz, Jessica A. Reese, Jean A. Leidner, Janis E. Campbell, Amanda M. Fretts, Dorothy A. Rhoades. Adiposity measures and obesity-related cancer: A report from the Oklahoma Strong Heart Study and Strong Heart Family Study [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B098.

BDH1-mediated LRRC31 regulation dependent on histone lysine β-hydroxybutyrylation to promote lung adenocarcinoma progression.

Lung adenocarcinoma (LUAD) is the most common form of lung cancer, with a consistently low 5-year survival rate. Therefore, we aim to identify key genes involved in LUAD progression to pave the way for targeted therapies in the future. BDH1 plays a critical role in the conversion between acetoacetate and β-hydroxybutyrate. The presence of β-hydroxybutyrate is essential for initiating lysine β-hydroxybutyrylation (Kbhb) modifications. Histone Kbhb at the H3K9 site is attributed to transcriptional activation. We unveiled that β-hydroxybutyrate dehydrogenase 1 (BDH1) is not only conspicuously overexpressed in LUAD, but it also modulates the overall intracellular Kbhb modification levels. The RNA sequencing analysis revealed leucine-rich repeat-containing protein 31 (LRRC31) as a downstream target gene regulated by BDH1. Ecologically expressed BDH1 hinders the accumulation of H3K9bhb in the transcription start site of LRRC31, consequently repressing the transcriptional expression of LRRC31. Furthermore, we identified potential BDH1 inhibitors, namely pimozide and crizotinib, which exhibit a synergistic inhibitory effect on the proliferation of LUAD cells exhibiting high expression of BDH1. In summary, this study elucidates the molecular mechanism by which BDH1 mediates LUAD progression through the H3K9bhb/LRRC31 axis and proposes a therapeutic strategy targeting BDH1-high-expressing LUAD, providing a fresh perspective for LUAD treatment.

P2RY13 is a prognostic biomarker and associated with immune infiltrates in renal clear cell carcinoma: A comprehensive bioinformatic study.

Clear cell renal cell carcinoma (ccRCC) is a common and aggressive form of cancer with a high incidence globally. This study aimed to investigate the role of P2RY13 in the progression of ccRCC and elucidate its mechanism of action. Gene Expression Omnibus and The Cancer Genome Atlas databases were used to extract gene expression profiles of ccRCC. These profiles were annotated and visualized by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses, as well as Gene Set Enrichment Analysis (GSEA). The STRING database was used to establish a protein-protein interaction network and to analyze the functional similarity. The GEPIA2 database was used to predict survival associated with hub genes. Meanwhile, the TIMER2.0 database was used to assess immune cell infiltration and its link with the hub genes. Immunohistochemistry (IHC) was used to determine the difference between ccRCC and adjacent normal tissue. We identified 272 differentially expressed genes (DEGs). GO and KEGG analyses suggested that DEGs were primarily involved in lymphocyte activation, inflammatory response, immunological effector mechanism pathways. By cytohubba, the 20 highest-scoring hub genes were screened to identify critical genes in the protein-protein interaction network linked with ccRCC. Resting dendritic cells, CD8 T cells, and activated mast cells all showed a significant positive correlation with these hub genes. Moreover, a higher immune score was associated with increased prognostic risk scores, which in turn correlated with a poorer prognosis. IHC revealed that P2RY13 was expressed at higher levels in ccRCC compared to para-cancer tissues. Identifying the DEGs will aid in the understanding of the causes and molecular mechanisms involved in ccRCC. P2RY13 may play a pivotal role in the progression and prognosis of ccRCC, potentially driving carcinogenesis though immune system mechanisms.

Abstract A028: Defining immune pathways involved in the depletion of B-cell precursor acute lymphoblastic leukemia-initiating cells following early-life cytomegalovirus (CMV) infection in mice

Abstract Background: B-cell acute lymphoblastic leukemia (B-ALL) is one of the most common forms of childhood cancers. Epidemiological studies have shown contrasting results regarding the role of infections in the risk of leukemia, and there is still no clear explanation for the pro- or anti-leukemia effects. Aim: This study aimed to investigate the influence of cytomegalovirus (CMV) infection on the development of B-ALL and identify the underlying immune mechanisms involved. Materials and Methods: In this study, Eμ-Ret transgenic mice were used as a model for hyperdiploid B-ALL, and luciferase-tagged CMV was used as a common early-life infection. The impact of infection on different subsets of B cells and leukemic initiating cells (LICs) in the bone marrow and spleen of neonatal and adult mice was assessed using multicolor flow cytometry. To gain insights into the mechanisms that impact LICs after infection, we sorted LICs from the splenocytes of infected and non-infected RFP mice seven days after infection, and total RNA sequencing (RNA-seq) was performed for gene expression analysis. We used neutralizing antibodies to evaluate the role of different cytokines/chemokines in mediating LIC depletion in vivo. Results: Significant infection-induced depletion of preleukemic cells occurred in infected neonate Eμ-ret mice on BALBc, BALBc/FVB (F1) and BALBc/C57 (F1) backgrounds. This depletion showed an age-dependent pattern, with only infection in the first week after birth reducing the LICs numbers. Depletion of preleukemia was dependent on Stat4 and p40 homodimer/monomers, but not p40 heterodimers (IL-12 and IL-23). Several chemokines/cytokines, including IFNg and TNFa, showed high levels of expression in the serum of CMV-infected pups but not in adult mice. RNA sequencing indicated that IFNg and TNFa exerted a direct effect on preleukemic cells. In vivo neutralization of IFNg completely blocked the depletion effect of CMV infection. Further experiments confirmed that this cytokine works downstream of the Stat4 signaling pathway. Conclusion: This is the first model to study the impact of CMV infection and the time of its exposure on B-ALL initiating cells. The identified Stat4-, IL12p40 homodimer/monomer-, and IFNg- driven activities could inform future treatment and prevention approaches for B-ALL. Citation Format: Ali Farrokhi, Tanmaya Atre, Citlali Marquez1, Soren Gantt, Gregor Reid. Defining immune pathways involved in the depletion of B-cell precursor acute lymphoblastic leukemia-initiating cells following early-life cytomegalovirus (CMV) infection in mice [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2023 Oct 1-4; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Immunol Res 2023;11(12 Suppl):Abstract nr A028.

Targeting Bone Marrow Microenvironment for Treatment of High-Risk B-Cell Acute Lymphoblastic Leukemia

Introduction B-cell acute lymphoblastic leukemia (B-ALL) is the most common form of cancer in children, accounting for approximately 20% of all pediatric cancers. Although treatment of B-ALL represents one of the success stories of modern medicine with 5-year survival rates approaching 90%, some children continue to have a dismal prognosis, particularly those with high-risk genetic alterations in their ALL cells or those who relapse. The leukemia microenvironment is an attractive novel therapeutic target, especially for children with high-risk leukemia as dose-limiting toxicities of conventional chemotherapeutic agents have prevented further improvements in survival. Aims In this study, we investigate whether therapeutically targeting the bone marrow (BM) osteoclasts can improve treatment outcome for B-ALL and the mechanisms of crosstalk between osteoclasts and leukemia cells. Methods We have established syngeneic and patient-derived xenograft (PDX) models for high-risk B- ALL that recapitulate the clinical symptoms of bone loss. For in vitro experiments, leukemia cells were cultured with osteoclast-derived conditioned media (CM) for 3 days. Results To evaluate the therapeutic potential of targeting osteoclasts during leukemia development, we administered zoledronic acid (2ug 5 days/week for 2 weeks), a bisphosphonate inhibitor of osteoclastic bone resorption, alone and in combination with imatinib (100mg/kg daily for 28 days) or dasatinib (10mg/kg daily for 28 days) in our BCR-ABL1 + B-ALL syngeneic mouse model. We showed that zoledronic acid treatment significantly reversed leukemia-induced bone loss by attenuating osteoclast activity. Zoledronic acid alone was found to enhance event-free survival in leukemia-bearing mice and further improvement was shown in combination with imatinib (p<0.05) or dasatinib (p<0.01). In addition, we administered zoledronic acid alone and in combination with vincristine, dexamethasone, and L-asparaginase (VXL) in a relapsed B-ALL PDX model. We further demonstrated that zoledronic acid alone or in combination with VXL improved survival compared to mice treated with vehicle (p<0.001) or VXL alone (p<0.01), respectively. In the clinical setting, we assessed the feasibility and safety of incorporating zoledronic acid early into leukemia therapy in three children with B-ALL. The patients were undergoing induction or consolidation chemotherapy and were administered zoledronic acid at the same time. Zoledronic acid was well tolerated without any significant adverse effects, indicating the feasibility of safely administering zoledronic acid in combination with chemotherapy in children with ALL. To gain mechanistic insight into the effect of osteoclasts on leukemia cells, we compared the molecular profile of the leukemia cells cultured with CM and control media using RNA sequencing. There were 30 differentially expressed genes identified at the 5% false discovery rate with a log fold-change value ≥1 or ≤-1. KEGG pathway analysis revealed a significant difference in cell cycle pathway in leukemia cells cultured with CM compared to control. Biological process analysis showed a positive regulation of B-cell proliferation and negative regulation of lymphocyte apoptotic process in leukemia cells cultured with CM compared to control. To functionally examine the effect of osteoclasts on leukemia cells, we showed that osteoclast-derived CM significantly increased B-ALL cell proliferation, as demonstrated by increased cell number (p<0.001), as well as reduced cell percentages in G0/G1 phases and increased S+G2/M phases (p<0.05) via cell cycle analyses. Using annexin V and DAPI staining, we further demonstrated that there were more live cells and less apoptotic and dead cells when the leukemia cells were cultured with CM compared to control (p<0.001). Together, our findings suggest that soluble factors produced by osteoclasts promote leukemia cell proliferation and survival. Conclusion Our study reveals osteoclasts play a role in leukemogenesis and leukemia-induced bone loss, and that targeting osteoclasts can provide dual clinical benefit in terms of bone health and improved survival for children with high-risk B-ALL.

Long-term benefit of sotorasib in patients with KRAS G12C-mutated non-small-cell lung cancer: plain language summary.

This is a plain language summary of a study called CodeBreaK 100. The CodeBreaK 100 study included patients with non-small-cell lung cancer that had spread outside the lung (advanced). Lung cancer is one of the most common forms of cancer. CodeBreaK 100 specifically looked at patients with a particular change(mutation) in the KRAS gene resulting in the mutated protein called KRAS G12C. The KRAS G12C mutation can lead to development and growth of lung cancer. Patients received a treatment called sotorasib, which has accelerated approval or full approval in over 50 countries for patients with non-small-cell lung cancer with the KRAS G12C mutation. The CodeBreaK 100 study looked at whether sotorasib is a safe and effective treatment for advanced non-small-cell lung cancer. Sotorasib is designed to specifically target and lock the mutated KRAS protein in the inactive state to treat non-small-cell lung cancer. In total, 174 adults were treated with sotorasib. Treatment-related side effects were seen in 70% of patients and were severe in 21% of patients. The most common side effects included diarrhea, increased liver enzymes, nausea and tiredness. 70 (41%) patients responded to sotorasib and 144 (84%) patients had tumors that either remained stable or shrunk in size. 29 (41%) patients who responded to sotorasib responded for over 12months. After 2years, 9 patients with a response remained on sotorasib; there were no notable increases in tumor size or development of new tumors over this time. There were 5patients who received sotorasib for more than 2years and continued to respond. Long-term benefit was seen for some patients. Patients also benefitted from treatment when the tumor expressed different amounts of a protein called PD-L1.In total, 33% of patients were still alive after 2years. Results show the long-term benefit of sotorasib therapy for people with advanced KRAS G12C-mutated non-small-cell lung cancer. Clinical Trial Registration: NCT03600883 (CodeBreaK 100) (ClinicalTrials.gov).

Nonclinical factors associated with the treatment of older women with newly diagnosed low-grade ductal carcinoma insitu.

Ductal carcinoma in situ (DCIS) is the most common form of noninvasive breast cancer and is associated with an excellent prognosis. As a result, there is concern about overdiagnosis and overtreatment of DCIS because most patients with DCIS are treated as though they have invasive breast cancer and undergo either breast-conserving surgery (BCS)-most commonly followed by radiation therapy (RT)-or mastectomy. Little research to date has focused on nonclinical factors influencing treatments for DCIS. Population-based data were analyzed from five state cancer registries (California, Florida, New Jersey, New York, and Texas) on women aged 65 years and older newly diagnosed with DCIS during the years 2003 to 2014 using a retrospective cohort design and multinominal logistic modeling. The registry records with Medicare enrollment data and fee-for-service claims to obtain treatments (BCS alone, BCS with RT, or mastectomy) were merged. Surgeon practice structure was identified through physician surveys and internet searches. Patients of surgeons employed by cancer centers or health systems were less likely to receive BCS with RT or mastectomy than patients of surgeons in single specialty or multispecialty practices. There also was substantial geographic variation in treatments, with patients in New York, New Jersey, and California being less likely to receive BCS with RT or mastectomy than patients in Texas or Florida. These findings suggest nonclinical factors including the culture of the practice and/or financial incentives are significantly associated with the types of treatment received for DCIS. Increasing awareness and targeted efforts to educate physicians about DCIS management among older women with low-grade DCIS could reduce patient harm and yield substantial cost savings.

Economical Evaluation of Prostate Cancer Treatment Using Intensity-Modulated Radiation Therapy, 3-Dimensional Conformal Radiation Therapy and Radical Prostatectomy: A Systematic Review

ObjectivesProstate cancer is a common form of cancer among men worldwide. The objective of this study was to conduct a systematic review of the economic evaluations of prostate cancer treatment strategies. MethodsThis systematic review was conducted using multiple electronic databases up to May 2021. English-language economic evaluation studies that compared intensity-modulated radiation therapy (IMRT), 3-dimensional conformal radiation therapy (3DCRT), and radical prostatectomy (RP) were included. The studies were evaluated using the Consolidated Health Economic Evaluation Reporting Standards checklist. The search yielded 1151 potentially relevant publications, which were screened based on the title and abstract. After the removal of duplicates, 55 studies remained, and 9 studies were screened in full text. Finally, textual data were analyzed manually using by-content analysis method. ResultsAll studies were cost-effective and evaluated quality-adjusted life year as the efficacy indicator. The studies were conducted from either payers' or health systems' perspectives, and the time horizon varied from 5 to 20 years. We included only full economic evaluation studies. The use of IMRT in comparison with 3DCRT was evaluated in 6 studies, based on which IMRT increased health and reduced side effects of treatment. According to incremental cost-effectiveness ratio (ICER) results, IMRT was more cost-effective than 3DCRT. Three studies evaluated the use of RP in comparison with radiotherapy. Based on these studies, radiotherapy was more effective than RP. ConclusionIMRT was found to be more cost-effective than 3DCRT in all 6 studies compared with the threshold. Radiotherapy was found to be more effective than RP. However, long-term clinical trial studies are needed to confirm these findings and to provide more definitive conclusions.

Long or short? Telomere length and pancreatic cancer and its precursor lesions, a narrative review

Abstract Pancreatic ductal adenocarcinoma (PDAC) is the most common and lethal form of pancreatic cancer, with a survival approaching only 11% at 5 years after diagnosis. In the last 15 years, telomere length (TL) measured in leukocyte (LTL) has been studied in relation to PDAC risk. The majority of the studies reported an association between short LTL and increased PDAC risk, but the results are heterogeneous. Genome-wide association studies have identified several single-nucleotide polymorphisms (SNPs) in the telomerase reverse transcriptase (TERT) gene as susceptibility loci for PDAC. Polygenic risk scores computed using SNPs associated with LTL have been tested in relation to PDAC susceptibility with various methods and giving contrasting results. The aim of this review is to analyze all publications carried out specifically on LTL, considering LTL measured with qPCR and with genetic proxies, and PDAC risk. Additionally, we will give an overview of the most relevant associations between SNPs in telomere-associated genes and PDAC, to answer the question shorter or longer? Which one of the two is associated with PDAC risk?

SAMD13 serves as a useful prognostic biomarker for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the most common form of liver cancer and the 5-year relative overall survival (OS) rate is less than 20%. Since there are no specific symptoms, most patients with HCC are diagnosed in an advanced stage with poor prognosis. Therefore, identifying novel prognostic biomarkers to improve the survival of patients with HCC is urgently needed. In the present study, we attempted to identify SAMD13 (Sterile Alpha Motif Domain-Containing Protein 13) as a novel biomarker associated with the prognosis of HCC using various bioinformatics tools. SAMD13 was found to be highly expressed pan-cancer; however, the SAMD13 expression was significantly correlated with the worst prognosis in HCC. Clinicopathological analysis revealed that SAMD13 upregulation was significantly associated with advanced HCC stage and high-grade tumor type. Simultaneously, high SAMD13 expression resulted in association with various immune markers in the immune cell subsets by TIMER databases and efficacy of immunotherapy. Methylation analysis showed SAMD13 was remarkably associated with prognosis. Furthermore, a six-hub gene signature associated with poor prognosis was correlated with the cell cycle, transcription, and epigenetic regulation and this analysis may support the connection between SAMD13 expression and drug-resistance. Our study illustrated the characteristics of SAMD13 role in patients with HCC using various bioinformatics tools and highlights its potential role as a therapeutic target and promising biomarker for prognosis in HCC.

Optimal Solution for Segmentation of Malignant Melanoma Dermoscopic Images

Melanoma Malignant (MM) is the most common and dangerous form of skin cancer, which is analyzed by using Dermoscopic images in computer sciences. Segmentation technique is used to separate lesion part from healthy part in Dermoscopic images. In this research, comparison of different most popular segmented Dermoscopic image technique like Type-2 Fuzzy, Hybrid Threshold, Wavelet, Gradient Vector Flow (GVF), and Watershed etc. is approached and then better segmentation technique is proposed. In these segmentation techniques different issues like problem of hair, different color lesion, specular reflection and smoothing transaction between lesion and skin were not taken under consideration. Our methodology involves three levels of hierarchy. In the preprocessing step, it deals with problem of hair, bubble noise, smoothing and reflection noise in Dermoscopic images. These noise removals are achieved by using different filters like “Derivative of Gaussian filter and Bootomhat filter”. After region of interest is extracted then combination of threshold, image enhancement and morphological filter are used to produce the efficient algorithm for segmentation. At the end step, segmented crop image is compared with dice coefficient and experimental results of gross error rate are evaluated. For this purpose, PH² Dataset is used that contains 200 Dermoscopic images with the lesion images. The lesion images are extracted by the expert dermatologists.

Inhibition of autophagy initiation: A novel strategy for oral squamous cell carcinomas

BackgroundOral squamous cell carcinoma (OSCC) is one of the most common forms of oral cancer and is known to have poor prognostic outcomes. Autophagy is known to be associated with aggressive tumor biology of OSCC. Hence, this study aimed to develop a novel therapeutic strategy against OSCC by targeting the autophagic pathway. MethodsImmunoblotting, and confocal microscopy were used to examine the effect of tumor microenvironmental stressors on the autophagy activity. Cellular proliferation and migration assays were performed to assess the anti-cancer activity of standard chemotherapy and autophagy initiation inhibitors, either alone or in combination. High resolution mass-spectrometry based proteomic analysis was utilized to understand the mechanisms behind chemoresistance in OSCC models. Finally, immunohistochemistry was performed to determine associations between autophagy markers and clinicopathological characteristics. ResultsTumor microenvironmental stressors were shown to induce autophagy activity in OSCC cell lines. Novel combinations of chemotherapy and autophagy inhibitors as well as different classes of autophagy inhibitors were identified. Combination of MRT68921 and SAR405 demonstrated marked synergy in their anti-proliferative activity and also showed synergy with chemotherapy in chemoresistant OSCC cell models. Autophagy was identified as one of the key pathways involved in mediating chemoresistance in OSCC. Furthermore, TGM2 was identified as a key upstream regulator of chemoresistance in OSCC models. Finally, positive staining for autophagosome marker LC3 was shown to be associated with low histological grade OSCC. ConclusionIn conclusion, this study identified a combination of novel autophagy inhibitors which can potently inhibit proliferation of both chemosensitive as well as chemoresistant OSCC cells and could be developed as a novel therapy against advanced OSCC tumors.

TMIC-41. LATERAL VENTRICLE PROXIMITY OF GLIOBLASTOMA IS ASSOCIATED WITH LOCALIZED MALIGNANCY-PROMOTING MOLECULAR SIGNATURES IN IMAGE-GUIDED BIOPSIES

Abstract Glioblastoma (GBM) is the most devastating and common form of primary brain cancer in adults. Tumor location plays a significant role in patient prognosis; in particular, GBM tumors contacting the lateral ventricles (LVs) are more aggressive than LV-distal counterparts. This may be due to interaction of tumors with unique features of the LV microenvironment, including the cerebrospinal fluid (CSF) and neural progenitor cells (NPCs) of the subventricular zone. Despite LV contact having a role on tumor malignancy, studies using bulk tumor samples to identify molecular contributors to LV-contacting prognosis have been only moderately successful, in large part due to intratumoral heterogeneity. Here, we leverage intraoperative surgical navigation to collect matched biopsies of adult LV-contacting primary GBM at locations proximal (< 2 cm) and distal ( > 2 cm) from the LV. Matched samples were collected from ten patients with equal sex distribution and an age range of 46 to 81 years. RNA sequencing of biopsies revealed a localized transcriptional signature of gene expression in LV-proximal locations. These genes include those identified to be associated with GBM malignancy and upregulated in primary GBM cells by CSF exposure or co-culture with NPCs, such as SERPINA3, CD44, and CTSB, as well as many newly identified genes. Implicated biological pathways involved in this transcriptional signature involve inflammation, chemotaxis, Notch signaling, angiogenesis, integrin signaling, and more. The top 50 upregulated genes by LV-proximity of GBM were used to cluster patient transcriptomes from the TCGA GBM database and evaluate the contribution to patient outcome. This analysis revealed a cluster with significantly extended overall survival that displayed a general downregulation of LV-proximity genes. Ultimately, these studies provide evidence that regional tumoral analysis is essential in identifying molecular signatures associated with microenvironmental influence, and that LV-contacting GBM has regional gene expression changes in many genes associated with malignancy.

DISP-01. THE IMPACT OF COVID-19 PANDEMIC ON THE HEALTHCARE DELIVERY OF RACIAL/ETHNIC MINORITIES WITH BRAIN METASTASIS BY FACILITY TYPE

Abstract OBJECTIVES Brain metastases (BM) are the most common form of adult brain cancer and one of the most devastating complications of cancer. We propose to characterize the effect of the pandemic on health care delivery for racial/ethnic underserved populations on BM care in general and stratifying by facility type. METHODS We utilized two national-scale datasets - the National Cancer Database (NCDB) and one of the largest COVID-19 real-time centralized data in the world - the National COVID Cohort Collaborative (N3C) database. Multivariable binary logistic regression models were performed to determine whether the pandemic (three-dimensional measures: pre-pandemic vs. during-pandemic, COVID-19 positivity, and density of COVID-19 prevalence) influence BM care delivery [including stereotactic radiosurgery (SRS), chemotherapy, and immunotherapy], especially for race/ethnicity minorities and patients receiving treatments at non-academic centers (NACs). RESULTS Compared to pre-pandemic years, the proportions of receiving BM care significantly decreased across all racial/ethnic groups during the pandemic using two nationwide datasets (NCDB: N=5238; N3C: N=13106), but non-white patients were still significantly less likely to undergo SRS than non-Hispanic whites (NHW) in N3C (total: aOR-0.76, p< 0.001; Black: aOR-0.78, p< 0.001, Hispanic: aOR-0.75, p=0.013; APAA: aOR-0.62, p=0.002) and NCDB (Black: aOR-0.78, p=0.006). Similarly, the odds of receiving chemotherapy for race/ethnicity minorities BM patients were significantly lower than NHW in N3C (Black: aOR-0.71, Hispanic: aOR-0.63, APAA: aOR-0.46, all p< 0.001) and NCDB (Black: aOR-0.86, p=0.028). Furthermore, such inequality in SRS receipt by race/ethnicity was exacerbated during the pandemic at NACs over academic centers (ACs) (esp. Hispanic vs. NHW at NACs: aOR-0.58, p=0.004; Hispanic vs. NHW at ACs: aOR-0.88, p=0.380) in NCDB. CONCLUSION Our study suggests that BM healthcare delivery has been significantly reduced in general during the pandemic, but racial/ethnic disparities in BM care and inequality in healthcare access by facility type still exist and have been even exacerbated.

Exploring The Impact of Capecitabine Treatment on Hormonal and Biochemical Markers in Women with Breast Cancer

Cancer antigen 15-3 (CA15-3) is a widely used tumor marker, and the serum level of this tumor marker is measured periodically in breast cancer patients during the chemotherapy period by capecitabine , Assuming that the higher serum levels of this tumor marker can be a potential risk in breast cancer patients, the study aimed to examine the effect on capecitabine with Ca15.3, serum estradiol, and calcium levels in postmenopausal women with breast cancer. The study was conducted on a total of 200 women, including 100 women without breast cancer who served as a control group aged range from (45-75years) and 100 women with breast cancer whose ages ranged from (40-70years). Patients at the oncology center at Imam al-Hussain medical city in Kerbala, Iraq, were sorted into groups based on their age, body mass index, disease duration, and treatment length for this study, which was done between July 2022 and October 2022, the efficacy of capecitabine, the plasma levels of (estradiol, Ca 15.3, and calcium) were measured in 100 breast cancer patients who had been taking the drug for at least 3 months. The findings revealed a statistically significant increase (p 0.05) in the concentration of Ca15.3 levels in women with breast cancer compared with control group, breast cancer (BC) is the most common form of cancer that results, and the average levels of serum calcium and estradiol were increased in patient had breast cancer chemotherapy and different with normal range, otherwise, the average level of serum calcium and estradiol in control groups within the normal range.in conclusion According to the ca15.3,serum calcium and estradiol levels, The high stability and existence of Ca15.3, serum calcium and estradiol in body serum make them a promising new diagnostic biomarker for breast cancer patients.

Optimization of Automated Radiosynthesis of Gallium-68-Labeled PSMA11 with Two [68Ge]Ge/[68Ga]Ga Generators: Fractional Elution or Prepurification?

Prostate cancer is one of the most common forms of cancer in men. An imaging technique for its diagnosis is [68Ga]-prostate-specific membrane antigen ([68Ga]Ga-PSMA-11) positron emission tomography (PET). To address the increasing demand for [68Ga]-labeled peptides and reduce the cost of radiosynthesis, it is therefore necessary to optimize the elution process of [68Ge]Ge/[68Ga]Ga generators. This study aims to identify the most effective approach for optimizing radiosynthesis using double elution in parallel of two [68Ge]Ge/[68Ga]Ga generators. Two methods have been tested: one using prepurification, and the other using fractionated elution. Five synthesis sequences were conducted using each method. The mean labeling yields for double elution with prepurification were 45.8 ± 29.4 (mean ± standard deviation) and none met the required criteria. The mean labeling yields for the fractionated double elution were 97.5 ± 1.9 (mean ± standard deviation) meeting the criteria, significantly superior to the prepurification method (p = 0.012), and similar to those of simple elution. This study showed that fractionated double elution from [68Ge]Ge/[68Ga]Ga generators produced a significantly higher labeling yield than double elution with prepurification, resulting in a larger activity recovered via radiosynthesis, thereby allowing more diagnostic tests to be performed.