bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1999: The impact of the COVID-19 pandemic on 30-day survival in pediatric cancer patients in low, middle, and high-income countries: an international, observational cohort study
Authors: Elhadi Muhammed , Bandyopadhyay Soham , Peter Noel , Lakhoo Kokila ,   Global Children's NCDs Collaborative
Published: June 2022

Abstract
Objectives: To conduct the first international cohort study to ascertain the short-term outcome for pediatric oncology patients who underwent treatment across 16 high-income countries (HICs) and 23 low- and- middle-income countries (LMICs) during the COVID-19 pandemic. The hypotheses being tested was that the COVID-19 pandemic had affected paediatric cancer care, and that the outcomes of children were worse in LMICs.
Design: A multicenter, international, collaborative cohort study.
Setting: 91 hospitals and cancer centers in 39 countries providing cancer treatment to pediatric patients between March and December 2020.
Participants: Patients were included if they were under the age of 18 years, and newly diagnosed with or undergoing active cancer treatment for Acute lymphoblastic leukemia, Non-Hodgkin lymphoma, Hodgkin lymphoma, Wilms Tumor, Sarcoma, Retinoblastoma, Gliomas, Medulloblastomas or Neuroblastomas, in keeping with the World Health Organization Global Initiative for Childhood Cancer.
Main outcome measure: All-cause mortality at 30 days and 90 days.
Results: 1660 patients were recruited. Over 30 days, 45 LMIC patients (4.3%; 95% CI: 3.1 to 5.5) and 2 HIC patients (0.4%; 95% CI: -0.1 to 0.9) died. 219 children had their treatments delayed, interrupted, or modified. LMIC patients had 11.7 (95% CI: 10.3 to 13.1) and 7.4 (95% CI: 6.5 to 8.3) times the risk of death at 30 days and 90 days respectively (p &lt; 0.001). After adjusting for confounders, pediatric cancer patients in LMICs had 35.7 times the odds of death at 30 days (p &lt; 0.001).
Conclusions: The COVID-19 pandemic has affected pediatric oncology service provision. It has disproportionately affected patients in LMICs, highlighting and compounding existing disparities in healthcare systems globally that need addressing urgently. However, most pediatric cancer patients continued to receive their normal standard of care. This speaks to the adaptability and resilience of health-care systems and healthcare workers globally.
Citation Format: Muhammed Elhadi, Soham Bandyopadhyay, Noel Peter, Kokila Lakhoo, Global Children's NCDs Collaborative. The impact of the COVID-19 pandemic on 30-day survival in pediatric cancer patients in low, middle, and high-income countries: an international, observational cohort study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1999.
Abstract 219: Towards targeted-gold nanoparticle enhanced chemoradiation therapy of pancreatic cancer
Authors: Papineni Rao V. , Adhikary Amitava , Bhattacharya Santanu 
Published: June 2022

Abstract
The goal of this project is to develop a unique pancreatic cancer treatment platform where, X-ray excited Targeted-Gold nanoparticles (T-GNPs) trigger and enhance drug action (I-RaGAZ, Integrated radiation combined with T-GNP and 2-Azido-2-deoxy-D-glucose (2-AZ-2-DG)). Herein, we plan to utilize a novel three stage nanotechnology-chemoradiation combinatorial approach for enhancing catastrophic cell death in pancreatic tumors and reducing normal tissue toxicity. T-GNP has cytotoxic effect at tumor site and can specifically sensitize tumor tissue for radiation. In this work, we used our GNP-based pancreatic ductal adenocarcinoma (PDAC) -specific drug delivery platform using a plectin-1-targeting peptide (PTP) (patent: US2018/0333432 A1) to demonstrate the cytotoxicity of the nanocomplex in vitro. In PANC-1 cancer cell model, using traditional gold-standard clonogenic assay, we show 2-AZ-2-DG has radiation-mediated cytotoxicity which is further augmented by T-GNP. These results align with our hypothesis and the electron spin resonance (ESR) spectroscopy electron-induced aminyl radical production data presented here. This radiation-produced auger electrons from T-GNP likely increased formation of RNH• which result in enhanced cell kill. This via H-atom abstraction reactions that might cause DNA-strand breaks and/or crosslink formation leading to lesions that could induce apoptosis of cancer cells.
This nanotool paraphrased as I-RaGAZ, Integrated radiation induced T-GNP - 2-AZ-2-DG anti-tumor action, will be very useful for treating deep-seated tumors with minimum collateral damage. This approach, integrated radiation-mediated azido tumor cure (I-RaGAZ), has vast global cancer treatment potential considering the dual mode of damaging the tumor tissues and protecting the normal tissues/organs.
Citation Format: Rao V. Papineni, Amitava Adhikary, Santanu Bhattacharya. Towards targeted-gold nanoparticle enhanced chemoradiation therapy of pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 219.
Abstract 2194: Rapid interrogation of colon cancer driver genes in vivo using split Cre and CRISPR-Cas9
Authors: Zhang Daniel , Westcott Peter , Naranjo Santiago , Hauck Haley , Rideout William , Sacks Nate , Bhutkar Arjun , Patten Justin , Goto Norihiro , Sedlak Joseph , Jacks Tyler 
Published: June 2022

Abstract
Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide, with a five-year survival rate of only 63% with current treatment regimens. While genetically engineered mouse models (GEMMs) have contributed widely to our understanding of the underlying genetics and molecular mechanisms of the disease, major limitations exist. Most models of CRC lack flexibility to initiate focal adenocarcinomas with different genetic perturbations within the native microenvironment of the distal colon. Specifically, no autochthonous model of metastatic CRC compatible with in vivo CRISPR-Cas9 genome engineering has been described. Therefore, we developed a novel split Cre-recombinase system restricting activation of oncogenic KrasG12D and deletion of the tumor suppressor gene (TSG) Trp53 to Lgr5+ stem cells of the colon crypts. Importantly, these events are not only critical drivers of CRC progression and metastasis in mice and humans but can also lead to non-specific transformation of the surrounding colonic stroma. By expressing one half of Cre from the endogenous Lgr5 locus and other half via colonoscopy-guided submucosal injection of lentivirus, we restricted Cre-mediated recombination to enterocytes. Lentivirus was also engineered to express a single guide RNA (sgRNA) against Apc, facilitating tumor initiation via deletion of this critical CRC TSG in mice expressing Cas9. A second sgRNA was included to facilitate rapid interrogation of putative cancer driver genes. As proof-of-principle, we targeted Smad4, a critical suppressor of metastasis in CRC, and observed adenocarcinoma formation and liver metastases with complete recombination and editing of all targeted genes. To prioritize candidate TSGs for future in vivo interrogation, we applied MutSigCV to large human sequencing datasets and identified genes significantly co-mutated with APC and KRAS in CRC. Altogether, this faithful and tractable model of CRC can be used for rapid functional interrogation of TSGs and should accelerate downstream mechanistic and preclinical studies.
Citation Format: Daniel Zhang, Peter Westcott, Santiago Naranjo, Haley Hauck, William Rideout, Nate Sacks, Arjun Bhutkar, Justin Patten, Norihiro Goto, Joseph Sedlak, Tyler Jacks. Rapid interrogation of colon cancer driver genes in vivo using split Cre and CRISPR-Cas9 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2194.
Abstract 2231: Surface-enhanced Raman scattering paltform of nanometal for exosome analysis in hepato-cellular carcinoma
Authors: Ahmed Ola Sayed , imam hisham , zekri abdel Rahman 
Published: June 2022

Abstract
Exosomes could be a source of cancer biomarkers in the future. Exosomes derived from tumors could provide a non-invasive way to diagnose cancer, assess cancer progression, and track treatment responses. However, exosome analysis would be aided by new molecular methods, which would speed up basic and clinical exosome research. Exosome research is rapidly advancing, providing new insights into the physiological role of exosomes and their significant link to human health. Although tumor-derived exosomes have been shown to be promising biomarkers for cancer detection and disease progression due to their inherited biological contents from the parent cancer cells and unique roles in tumor metastasis and invasion, rapid and effective isolation from complex biological samples and high-precision real-time analysis remains a difficult task. In this work, we present a surface-enhanced Raman scattering (SERS) platform for integrating multiple hepatocellular carcinoma exosomes conventional method to read different peak positions and amplitudes of spectrum, whole SERS spectra of exosomes were analyzed by principal component analysis (PCA). In addition, label-free analysis of purified exosomes from normal cell and hepatocellular carcinoma were clearly distinguished from normal cell derived exosomes by 96.4% sensitivity and 98.2% specificity using surface-enhanced Raman spectroscopy (SERS). In this study, the possibility of using exosomes as biomarkers for the detection of hepatocellular carcinoma (HCC) was discussed. From this study, SERS can serve as a valuable tool for separating exogenous subpopulations and can be used to characterize exosomes for cancer diagnosis.
Citation Format: Ola Sayed Ahmed, hisham imam, abdel Rahman zekri. Surface-enhanced Raman scattering paltform of nanometal for exosome analysis in hepato-cellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2231.
Abstract 2239: Detecting cancer when it can be cured: The potential for cure across all stageable cancers
Authors: Hubbell Earl , Clarke Christina 
Published: June 2022

Abstract
Introduction: Early detection of cancer may reduce cancer mortality by providing access to treatments with the potential to cure cancer at early stages. A mixture cure model divides cancer cases into two populations: one where cancer is likely to severely impact mortality (not-cured) and one where long-term survival with low risk is possible (cured). Previous work on such models has concentrated on estimating cure for either many cancer types without regard to stage (public health arena), or single cancers by stage at diagnosis (screening arena). A gap in the current literature is an estimation of likelihood of cure in many cancer types at all stages.
Methods: We estimate a mixture-cure model for all stages simultaneously for stageable cancers using the fact that cancer is a progressive disease (worse by stage) as a constraint on model parameters. We applied this estimation procedure to 21 cancer classes with standard American Joint Committee on Cancer (AJCC) staging using 12 years of cancer-specific survival data in 50-79 year old individuals using Surveillance, Epidemiology and End Results (SEER) program data from 2006-2015 followed to 2018. For each stage, we recover the fraction of those cured (“cure fraction”, i.e., long-term survivors with minimal excess hazard) and not-cured (severe acute mortality due to cancer, modeled as a Weibull distribution).
Results: Cure fractions varied between cancer classes. Two important types of cancer behavior are illustrated by colorectal and gallbladder cancers. Colorectal cancer had a good potential for cure at any stage before metastasis, with a precipitous drop from 63% (95% CI: 62-64%) cure at stage III to 7% (6-7%) cure at stage IV. In contrast, gallbladder cancer exhibited a systematic decrease at each stage, with 47% (43-52%) cure fraction at stage I, 22% (20-24%) at stage II, 20% (17-22%) at stage III, and 2% (2-3%) at stage IV. Differences in 5-year survival between earlier stages and metastasis were highly correlated to differences in cure fraction (r^2=0.97), suggesting differences in 5-year survival are a proxy for differences in cure.
Conclusions: Long-term survivors were evident at early stages for all 21 cancer types examined. These survival fractions were all greatly reduced by the time cancer reached metastasis. This indicates early-stage cancers do not differ from late-stage cancers simply by lead time and provides statistical evidence that detection of cancer in early stages may result in long-term survival for many stageable cancer types.
Citation Format: Earl Hubbell, Christina Clarke. Detecting cancer when it can be cured: The potential for cure across all stageable cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2239.
Abstract 2316: Malignant potential of colorectal adenoma based on the telomere length
Authors: Tomasova Kristyna , Kroupa Michal , Siskova Anna , Horak Josef , Vycital Ondrej , Liska Vaclav , Vodickova Ludmila , Vodicka Pavel 
Published: June 2022

Abstract
Telomere attrition is a well-known hallmark of malignancy in cancer tissue. Our study analyzed the relative telomere length in adenomas, precursor lesions of colorectal adenocarcinoma. We investigated if the accelerated telomere length shortening occurs before potential malignant transformation to adenocarcinoma and corresponds with clinicopathological characteristics.
Relative telomere length was measured in 145 patients using multiplex qPCR. We have recorded significant shortening of telomeres in the adenoma tissue compared to adjacent mucosa (Wilcoxon Signed Rank test, p &lt; 0.0001). Further, we have observed a weak inverse relationship between both adenoma and mucosa telomere length and age (Spearman's and Pearson's correlation, p = 0.021 and p = 0.027, respectively), contrary to our previous study of colorectal cancer patients (n = 696), where the inverse correlation of telomere length was detected only in the non-malignant mucosa (Pearson's correlation, p = 0.029). However, the telomere length ratio of adenoma to adjacent mucosa did not correspond with the degree of dysplasia according to the Vienna classification (Kruskal-Wallis test, p = 0.572). Also, there was no difference in the telomere length ratio among histological types of adenomas and no association with the adenoma localization in proximal and distal colon or rectum (Kruskal-Wallis test, p = 0.648 and p = 0.459, respectively).
Preliminary results indicate that telomere shortening occurs indeed as early as in a stage of adenomatous polyps, and it is less pronounced in adenomas compared to cancerous cells. However, the relative telomere length does not seem to correspond with adenoma progression towards malignancy. In planned experiments, we intend to assess mitochondrial DNA damage caused by 8-oxoguanine DNA adducts. These major oxidative base lesions can arise from endogenous reactive oxygen species and impact, among other things, the integrity of telomeres through double-strand breaks to DNA. Mitochondrial DNA is more prone to accumulation of oxidative damage than nuclear DNA and thus might be useful as an early, additional indicator of the precancerous character of adenoma. The study will reveal whether increased mitochondrial DNA damage and telomere loss are commonly present and linked together in adenomas.
This study was supported by the Charles University (project GA UK No. 120, UNCE/MED/006) and the Grant Agency of the Czech Republic (21-04607X, 21-27902S).
Citation Format: Kristyna Tomasova, Michal Kroupa, Anna Siskova, Josef Horak, Ondrej Vycital, Vaclav Liska, Ludmila Vodickova, Pavel Vodicka. Malignant potential of colorectal adenoma based on the telomere length [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2316.
Abstract 2416: Ras-mediated activation of mTORC2 drives breast cancer cell migration and invasion
Authors: Wiegand Mollie E. , Collins Shannon E. , Brown Isabella N. , Werner Alyssa N. , Mundo Isabelle M. , Mouneimne Ghassan , Charest Pascale G. 
Published: June 2022

Abstract
We previously identified the mechanistic Target of Rapamycin Complex 2 (mTORC2) as an effector of Ras for the control of directed cell migration in Dictyostelium. Recently, this relationship was found to be conserved in mammalian cells, and mTORC2 was shown to be an effector of oncogenic Ras. Deregulated mTORC2 signaling in cancer is mostly associated with increased survival and metabolic reprogramming, but mTORC2 has also been linked to cancer cell migration, particularly in breast cancer. Interestingly, although Ras is rarely mutated in breast cancer, it is often upregulated due to amplification and overexpression of growth factor receptors. Here, we investigated the role of Ras in promoting the migration and invasion of breast cancer cells through mTORC2. We observed that Ras and mTORC2 promote the migration of breast cancer cells, independently of the breast cancer molecular subtype. Using breast epithelial MCF10A cells transformed with HER2 or mutant Ras, we found that Ras promotes mTORC2 activation, and mTORC2-dependent migration and invasion. We further observed that while mutant Ras-transformed MCF10A cells display uncontrolled cell proliferation and an invasive phenotype, silencing of the mTORC2-dependent component Rictor mostly leads to loss of invasiveness. Together, our findings suggest that, whereas Ras activation of mTORC2 is likely to play a minor role in breast tumor formation, the Ras-mTORC2 pathway plays a key and general role in promoting the migration and invasion of breast cancer cells.
Citation Format: Mollie E. Wiegand, Shannon E. Collins, Isabella N. Brown, Alyssa N. Werner, Isabelle M. Mundo, Ghassan Mouneimne, Pascale G. Charest. Ras-mediated activation of mTORC2 drives breast cancer cell migration and invasion [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2416.
Abstract 2418: Markers for metastasis evaluation of the ErbB family and GDF15 inratosteosarcoma
Authors: Ishiyama Shun , West Bailey , Han Hyo-Jeong , Guo Xin , Ito Tomoaki , Saeki Harumi , Brock Malcolm V. , Gabrielson Kathleen 
Published: June 2022

Abstract
The most recent advance in the treatment of osteosarcoma (OS) occurred in the 1980s when multi-agent chemotherapy was shown to improve overall survival compared to surgery alone. Animal model investigations can accelerate the understanding of human diseases and since few models are available for OS, we refined a rat model to ask questions regarding pathways of metastasis and metastasis biomarker predictiveness. The outbred Sprague-Dawley (SD) rat model is an immunocompetent, syngeneic model, as we implant UMR106 OS cells (ATCC), which were originally isolated from a SD OS. We developed a reproducible method to orthotopically implant cells into the tibia microenvironment and to amputate the limb for longitudinal studies. Using young rats, we also modeled pediatric OS. We found that rats develop reproducible primary and metastatic pulmonary tumors which histologically resemble human primary and metastatic osteosarcoma. Using immunohistochemistry methods, we found that primary OS is infiltrated with numerous macrophages with relatively fewer CD3+ T cells. A protein expression survey of these OS cells revealed significant expression of ErbB family receptor tyrosine kinases (ErbB2, ErbB4), which have recently been shown to be anti-inflammatory against macrophages. We also discovered that rats with osteosarcoma have markedly high serum levels of Growth Differentiation Factor 15 (GDF15), also called Macrophage Inhibitory Cytokine 1, a member of the TGF beta family of proteins, which is also frequently expressed with ErbB2 in cancers. GDF15 was measured by ELISA. Western blot analysis showed that GDF15 precursor (pro-peptide) was expressed in primary and metastases. This model will enable studies with anti-ErbB2 or GDF15 pathway inhibition to assess the role of macrophage activation in the setting of pathway inhibition and chemotherapy, as well as how pathway inhibition modulates metastasis incidence. In vivo and invitro, systems will enable the assessment of the role of GDF15 as a potential biomarker of metastasis, compared to tibial radiographic patterns, serum alkaline phosphatase, and lung histopathology. In conclusion, we have an immunocompetent, syngeneic orthotopic osteosarcoma rat model which affectively resembles human osteosarcoma, and can be used for better understanding metastasis mechanisms and metastasis biomarkers.
Citation Format: Shun Ishiyama, Bailey West, Hyo-Jeong Han, Xin Guo, Tomoaki Ito, Harumi Saeki, Malcolm V. Brock, Kathleen Gabrielson. Markers for metastasis evaluation of the ErbB family and GDF15 inratosteosarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2418.
Abstract 2420: Exploring associations between the IL4 pathway and colorectal cancer risk in in vivo models and clinical records
Authors: Beckstead Jacob , Petros Jack , Mehrotra Kunaal , Fingleton Barbara 
Published: June 2022

Abstract
We have previously demonstrated that inhibition of the IL4 pathway limits metastatic potential in colorectal cancers and have postulated that the type II IL4 receptor could serve as a potential target in risk assessment and treatment. Here we expand on these findings through in vivo mouse studies and retrospective patient analysis. To elucidate how colorectal cancers may use the IL4 pathway to grow and infiltrate surrounding tissue, we performed two in vivo studies independently targeting IL4ra in myeloid and intestinal epithelial tissues. Mice with a deleted allele of IL4ra and a floxed allele of IL4ra were crossed with either a line expressing a myeloid-specific Cre (LysM Cre) or an intestinal epithelial-specific Cre (Villin Cre). Our results indicate that myeloid-expressed IL4ra facilitates tumorigenesis but is not a significant contributor to later growth. In contrast, epithelial IL4ra significantly contributes to tumor number and size, but had little effect on the observed number of aberrant crypt foci, an early indicator of colon cancer.
We hypothesized that effects of atypical IL4 activity could also be observed in the medical record. Atopic diseases such as asthma and eczema are characterized by an overabundance of IgE, a protein regulated by the IL4 pathway. Using Vanderbilt University Medical Center’s SD Discover program, we obtained de-identified records for patients diagnosed with at least stage II colorectal carcinoma between 2005 and 2015. We then stratified patients by metastatic progression. Patients who were diagnosed with asthma prior to age sixty were significantly less likely to develop an advanced form of colorectal cancer and at reduced risk of metastatic disease or recurrence. This may be a result of medication prescribed for atopic disease such as inhalers and corticosteroids and we are performing further analyses to test these hypotheses.
Citation Format: Jacob Beckstead, Jack Petros, Kunaal Mehrotra, Barbara Fingleton. Exploring associations between the IL4 pathway and colorectal cancer risk in in vivo models and clinical records [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2420.