@Article{info:doi/10.2196/66286, author="Luo, Jia-Yuan and Deng, Yu-Long and Lu, Shang-Yi and Chen, Si-Yan and He, Rong-Quan and Qin, Di-Yuan and Chi, Bang-Teng and Chen, Gang and Yang, Xia and Peng, Wei", title="Current Status and Future Directions of Ferroptosis Research in Breast Cancer: Bibliometric Analysis", journal="Interact J Med Res", year="2025", month="Feb", day="26", volume="14", pages="e66286", keywords="breast cancer", keywords="ferroptosis", keywords="bibliometric", keywords="malignancy", keywords="cancer studies", keywords="treatment", keywords="bibliometric analysis", keywords="VOSviewer", keywords="China", keywords="United States", keywords="breast carcinoma", keywords="mammary cancer", keywords="strategy", keywords="trends", keywords="bibliography", keywords="review", keywords="disparities", keywords="forecast", keywords="treatment strategies", keywords="advancements", abstract="Background: Ferroptosis, as a novel modality of cell death, holds significant potential in elucidating the pathogenesis and advancing therapeutic strategies for breast cancer. Objective: This study aims to comprehensively analyze current ferroptosis research and future trends, guiding breast cancer research advancements and innovative treatment strategies. Methods: This research used the R package Bibliometrix (Department of Economic and Statistical Sciences at the University of Naples Federico II), VOSviewer (Centre for Science and Technology Studies at Leiden University), and CiteSpace (Drexel University's College of Information Science and Technology), to conduct a bibliometric analysis of 387 papers on breast cancer and ferroptosis from the Web of Science Core Collection. The analysis covers authors, institutions, journals, countries or regions, publication volumes, citations, and keywords. Results: The number of publications related to this field has surged annually, with China and the United States collaborating closely and leading in output. Sun Yat-sen University stands out among the institutions, while the journal Frontiers in Oncology and the author Efferth T contribute significantly to the field. Highly cited papers within the domain primarily focus on the induction of ferroptosis, protein regulation, and comparisons with other modes of cell death, providing a foundation for breast cancer treatment. Keyword analysis highlights the maturity of glutathione peroxidase 4-related research, with breast cancer subtypes emerging as motor themes and the tumor microenvironment, immunotherapy, and prognostic models identified as basic themes. Furthermore, the application of nanoparticles serves as an additional complement to the basic themes. Conclusions: The current research status in the field of ferroptosis and breast cancer primarily focuses on the exploration of relevant theoretical mechanisms, whereas future trends and mechanisms emphasize the investigation of therapeutic strategies, particularly the clinical application of immunotherapy related to the tumor microenvironment. Nanotherapy has demonstrated significant clinical potential in this domain. Future research directions should deepen the exploration in this field and accelerate the clinical translation of research findings to provide new insights and directions for the innovation and development of breast cancer treatment strategies. ", doi="10.2196/66286", url="https://www.i-jmr.org/2025/1/e66286" } @Article{info:doi/10.2196/57379, author="Kim, Yesol and Kim, Geonah and Cho, Hyeonmi and Kim, Yeonju and Choi, Mona", title="Application of Patient-Generated Health Data Among Older Adults With Cancer: Scoping Review", journal="J Med Internet Res", year="2025", month="Feb", day="4", volume="27", pages="e57379", keywords="patient-generated health data", keywords="wearable devices", keywords="patient-reported outcomes", keywords="patient-centered care", keywords="older adults", keywords="cancer", keywords="scoping review", abstract="Background: The advancement of information and communication technologies has spurred a growing interest in and increased applications of patient-generated health data (PGHD). In particular, PGHD may be promising for older adults with cancer who have increased survival rates and experience a variety of symptoms. Objective: This scoping review aimed to identify the characteristics of research on PGHD as applied to older adults with cancer and to assess the current use of PGHD. Methods: Guided by Arksey and O'Malley as well as the JBI (Joanna Briggs Institute) methodology for scoping reviews, 6 electronic databases were searched: PubMed, Embase, CINAHL, Cochrane Library, Scopus, and Web of Science. In addition, the reference lists of the selected studies were screened to identify gray literature. The researchers independently screened the literature according to the predefined eligibility criteria. Data from the selected studies were extracted, capturing study, participant, and PGHD characteristics. Results: Of the 1090 identified studies, 88 were selected. The publication trend gradually increased, with a majority of studies published since 2017 (69/88, 78\%). Almost half of the studies were conducted in North America (38/88, 43\%), followed by Europe (30/88, 34\%). The most common setting in which the studies were conducted was the participant's home (69/88, 78\%). The treatment status varied; the median sample size was 50 (IQR 33.8-84.0). The devices that were used to measure the PGHD were classified as research-grade wearable devices (57/113, 50.4\%), consumer-grade wearable devices (28/113, 24.8\%), or smartphones or tablet PCs for mobile apps (23/113, 20.4\%). More than half of the studies measured physical activity (69/123, 56.1\%), followed by patient-reported outcomes (23/123, 18.7\%), vital signs (13/123, 10.6\%), and sleep (12/123, 9.8\%). The PGHD were mainly collected passively (63/88, 72\%), and active collection methods were used from 2015 onward (20/88, 23\%). In this review, the stages of PGHD use were classified as follows: (1) identification, monitoring, review, and analysis (88/88, 100\%); (2) feedback and reporting (32/88, 39\%); (3) motivation (30/88, 34\%); and (4) education and coaching (19/88, 22\%). Conclusions: This scoping review provides a comprehensive summary of the overall characteristics and use stages of PGHD in older adults with various types and stages of cancer. Future research should emphasize the use of PGHD, which interacts with patients to provide patient-centered care through patient engagement. By enhancing symptom monitoring, enabling timely interventions, and promoting patient involvement, PGHD have the potential to improve the well-being of older adults with cancer, contributing to better health management and quality of life. Therefore, our findings may provide valuable insights into PGHD that health care providers and researchers can use for geriatric cancer care. Trial Registration: Open Science Framework Registry OSF.IO/FZRD5; https://doi.org/10.17605/OSF.IO/FZRD5 ", doi="10.2196/57379", url="https://www.jmir.org/2025/1/e57379" } @Article{info:doi/10.2196/54086, author="Jain, Rishabh and Kumar, Akash and Sharma, Atul and Sahoo, Kumar Ranjit and Sharma, Aparna and Seth, Amlesh and Nayak, Brusabhanu and Shamim, A. Shamim and Kaushal, Seema and KP, Haresh and Das, J. Chandan and Batra, Atul", title="Carboplatin in Patients With Metastatic Castration-Resistant Prostate Cancer Harboring Somatic or Germline Homologous Recombination Repair Gene Mutations: Phase II Single-Arm Trial", journal="JMIR Res Protoc", year="2024", month="Apr", day="18", volume="13", pages="e54086", keywords="carboplatin", keywords="mCRPC", keywords="prostate cancer", keywords="homologous recombinant gene repair", keywords="metastatic castration-resistant prostate cancer", keywords="incurable", keywords="deleterious mutation", keywords="synthetic lethality", keywords="tumor", keywords="DNA", keywords="low-income", keywords="middle-income", keywords="chemotherapeutic", keywords="drug", keywords="retrospective study", keywords="taxane", keywords="novel antiandrogen", keywords="single-arm study", keywords="health-related", keywords="quality of life", keywords="bone lesion", abstract="Background: Approximately 20\%-25\% of patients with metastatic castration-resistant prostate cancer (mCRPC) harbor a deleterious germline or somatic mutation in the homologous recombination repair (HRR) pathway genes, which is involved in the repair of double-stranded DNA damage. Half of these mutations are germline, while the remaining are exclusively somatic. While polyadenosine 5'diphosphoribose [poly (ADP-ribose)] polymerase inhibitors, such as olaparib and rucaparib, are effective in this subgroup, their widespread use is limited due to the associated high cost, especially in resource-constrained settings. Notably, platinum agents like carboplatin have exquisite sensitivity to cells with defective DNA repair machinery. Carboplatin, a conventional, inexpensive chemotherapeutic agent, offers a potential alternative treatment in such patients. Several retrospective small case series support this hypothesis. However, there are no prospective clinical trials of carboplatin in patients with mCRPC with HRR mutations. Objective: The primary objective is to assess the objective response rate of 3 weekly carboplatin treatments in patients with mCRPC harboring deleterious mutations in the HRR pathway genes and previously treated with a taxane or a novel antiandrogen agent. The secondary objectives include progression-free survival, health-related quality of life, and safety profile of carboplatin. Methods: Patients diagnosed with mCRPC harboring HRR pathway mutations previously treated with docetaxel or novel antiandrogen agents (abiraterone, enzalutamide, apalutamide, or darolutamide) or both will be eligible. Genes involved directly or indirectly in the HRR pathway will be tested. In this single-arm phase II study, we will screen approximately 200 patients to enroll 49 patients, and carboplatin (dosing at the area under curve=5) will be administered every 3 weeks until progression or intolerable side effects. The primary end point will be assessed as the proportion of patients with a reduction of serum prostate-specific antigen by more than 50\% from enrollment. Secondary outcomes include progression-free survival---soft-tissue disease progression (by response evaluation criteria in solid tumors, version 1.1, and bone lesion progression using Prostate Cancer Clinical Trials Working Group 3 criteria), health-related quality of life during carboplatin treatment using the Functional Assessment of Cancer Therapy---Prostate questionnaire and the European Organisation for Research and Treatment of Cancer questionnaire and safety profile of carboplatin (National Cancer Institute's Common Terminology Criteria for Adverse Events version 5.0). Results: The trial started enrollment in September 2023. This trial is ongoing, and 12 patients have been recruited to date. All 49 participants will be enrolled according to plan. Conclusions: This prospective phase II trial represents a critical step toward addressing the therapeutic gap in patients with mCRPC harboring HRR pathway mutations, particularly in demographic regions with limited access to poly (ADP-ribose) polymerase inhibitors. Outcomes from this study will inform clinical practice and guide future phase III randomized trials, ultimately improving patient outcomes globally. Trial Registration: Clinical Trials Registry of India CTRI/2023/04/051507; https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=Njc0NjU=\&Enc=\&userName= International Registered Report Identifier (IRRID): DERR1-10.2196/54086 ", doi="10.2196/54086", url="https://www.researchprotocols.org/2024/1/e54086", url="http://www.ncbi.nlm.nih.gov/pubmed/38453159" } @Article{info:doi/10.2196/48127, author="Atiomo, William and Alqutami, Fatma and Albasha, Sara and Hachim, Mahmood", title="Deciphering the Role of Insulin-Like Growth Factor 1 in Endometrial Cancer in Patients With Polycystic Ovary Syndrome: Protocol for a Methodological Approach Using Cell Culture Experiments", journal="JMIR Res Protoc", year="2023", month="Nov", day="21", volume="12", pages="e48127", keywords="endometrial cancer", keywords="polycystic ovary syndrome", keywords="insulin-like growth factor-1", keywords="IGF-1", keywords="cell culture", keywords="United Arab Emirates", keywords="PCOS", keywords="women's health", keywords="gynecology", keywords="oncology", keywords="cancer", keywords="endocrinology", keywords="serum", keywords="endometrium", keywords="endometrial", keywords="cell", keywords="biology", keywords="gene", keywords="genetic", keywords="genetics", keywords="genes", abstract="Background: Endometrial cancer (EC) is the most common gynecological cancer in women globally. It is linked to increasing obesity rates and longer life spans. The molecular mechanisms leading to EC are unclear; however, women with polycystic ovary syndrome (PCOS) have a 3- to 5-fold increased EC risk. According to a pilot study conducted in the United Kingdom, insulin-like growth factor-1 (IGF-1) gene and protein were raised in the endometrium and blood of women with EC and PCOS, compared with those without PCOS (controls). Therefore, raised serum IGF-1 levels may contribute to an increased EC risk in women with PCOS, but it is necessary to test this hypothesis since not all studies have demonstrated this association. Objective: This study aims to investigate the role of IGF-1 in mediating EC risk in PCOS. This will be achieved by evaluating the proliferative effects of PCOS serum, IGF-1, and IGF-1 antagonist on human endometrial cancer 1-A and 1-B cell lines, with a comparison to controls (using serum from women without PCOS and cell culture media). The study will also identify differentially expressed genes and pathways activated by various treatments. Methods: We intend to recruit 20 women with PCOS and 20 women without PCOS for this cross-sectional study. All experiments will be carried out 4 times to ensure consistency. We will perform transcriptomic and phosphoproteomic profiling to identify differentially expressed genes and phosphoproteins between different treatments using RNA sequencing and phosphoproteomics. We will also perform bioinformatics pathway analysis to identify whether any unique collection of genes or phosphoproteins explains increased EC risk in PCOS. The primary outcome measure will be the cell proliferation (growth) difference measured by cell index values. Our protocol stands out due to its unique approach; no previous study has used this approach to investigate the oncogenic effect of serum from women with PCOS. Additionally, no previous study has considered the differential mutations of genes related to the insulin signaling pathway across various types of human EC cell lines and the potential impact of these variations on their experimental findings. Results: Participants are currently being recruited. It is expected that preliminary findings suitable for analysis and publication will be available by the summer of 2024. Conclusions: Although we currently do not have any results to report, sharing our protocol at this stage will aid in research collaboration, provide an opportunity for early feedback, and help reduce duplication of effort by other research groups. The findings of our study will have broader implications. A deeper understanding of the mechanisms underlying the regulation of the IGF system in PCOS and EC will improve our ability to develop effective treatment modalities for EC and will be a vital step toward reducing EC in women globally. International Registered Report Identifier (IRRID): DERR1-10.2196/48127 ", doi="10.2196/48127", url="https://www.researchprotocols.org/2023/1/e48127", url="http://www.ncbi.nlm.nih.gov/pubmed/37988160" } @Article{info:doi/10.2196/42254, author="Gallagher, Kevin and Bhatt, Nikita and Clement, Keiran and Zimmermann, Eleanor and Khadhouri, Sinan and MacLennan, Steven and Kulkarni, Meghana and Gaba, Fortis and Anbarasan, Thineskrishna and Asif, Aqua and Light, Alexander and Ng, Alexander and Chan, Vinson and Nathan, Arjun and Cooper, David and Aucott, Lorna and Marcq, Gautier and Teoh, Yuen-Chun Jeremy and Hensley, Patrick and Duncan, Eilidh and Goulao, Beatriz and O'Brien, Tim and Nielsen, Matthew and Mariappan, Paramananthan and Kasivisvanathan, Veeru", title="Audit, Feedback, and Education to Improve Quality and Outcomes in Transurethral Resection and Single-Instillation Intravesical Chemotherapy for Nonmuscle Invasive Bladder Cancer Treatment: Protocol for a Multicenter International Observational Study With an Embedded Cluster Randomized Trial", journal="JMIR Res Protoc", year="2023", month="Jun", day="15", volume="12", pages="e42254", keywords="TURBT", keywords="bladder cancer", keywords="quality improvement", keywords="performance feedback", keywords="transurethral resection", keywords="urology", keywords="oncology", keywords="recurrence", keywords="surgery", keywords="surgical", keywords="quality indicator", keywords="performance", keywords="feedback", keywords="evaluation", abstract="Background: Nonmuscle invasive bladder cancer (NMIBC) accounts for 75\% of bladder cancers. It is common and costly. Cost and detriment to patient outcomes and quality of life are driven by high recurrence rates and the need for regular invasive surveillance and repeat treatments. There is evidence that the quality of the initial surgical procedure (transurethral resection of bladder tumor [TURBT]) and administration of postoperative bladder chemotherapy significantly reduce cancer recurrence rates and improve outcomes (cancer progression and mortality). There is surgeon-reported evidence that TURBT practice varies significantly across surgeons and sites. There is limited evidence from clinical trials of intravesical chemotherapy that NMIBC recurrence rate varies significantly between sites and that this cannot be accounted for by differences in patient, tumor, or adjuvant treatment factors, suggesting that how the surgery is performed may be a reason for the variation. Objective: This study primarily aims to determine if feedback on and education about surgical quality indicators can improve performance and secondarily if this can reduce cancer recurrence rates. Planned secondary analyses aim to determine what surgeon, operative, perioperative, institutional, and patient factors are associated with better achievement of TURBT quality indicators and NMIBC recurrence rates. Methods: This is an observational, international, multicenter study with an embedded cluster randomized trial of audit, feedback, and education. Sites will be included if they perform TURBT for NMIBC. The study has four phases: (1) site registration and usual practice survey; (2) retrospective audit; (3) randomization to audit, feedback, and education intervention or to no intervention; and (4) prospective audit. Local and national ethical and institutional approvals or exemptions will be obtained at each participating site. Results: The study has 4 coprimary outcomes, which are 4 evidence-based TURBT quality indicators: a surgical performance factor (detrusor muscle resection); an adjuvant treatment factor (intravesical chemotherapy administration); and 2 documentation factors (resection completeness and tumor features). A key secondary outcome is the early cancer recurrence rate. The intervention is a web-based surgical performance feedback dashboard with educational and practical resources for TURBT quality improvement. It will include anonymous site and surgeon-level peer comparison, a performance summary, and targets. The coprimary outcomes will be analyzed at the site level while recurrence rate will be analyzed at the patient level. The study was funded in October 2020 and began data collection in April 2021. As of January 2023, there were 220 hospitals participating and over 15,000 patient records. Projected data collection end date is June 30, 2023. Conclusions: This study aims to use a distributed collaborative model to deliver a site-level web-based performance feedback intervention to improve the quality of endoscopic bladder cancer surgery. The study is funded and projects to complete data collection in June 2023. Trial Registration: ClinicalTrials.org NCT05154084; https://clinicaltrials.gov/ct2/show/NCT05154084 International Registered Report Identifier (IRRID): DERR1-10.2196/42254 ", doi="10.2196/42254", url="https://www.researchprotocols.org/2023/1/e42254", url="http://www.ncbi.nlm.nih.gov/pubmed/37318875" } @Article{info:doi/10.2196/45176, author="Sunami, Yoshiaki and Ronellenfitsch, Ulrich and Kleeff, Jorg and Rebelo, Artur", title="Fibroblast Activation Protein Overexpression in Gastrointestinal Tumors: Protocol for a Systematic Review and Meta-analysis", journal="JMIR Res Protoc", year="2023", month="Apr", day="26", volume="12", pages="e45176", keywords="fibroblast activation protein", keywords="cancer-associated fibroblasts", keywords="survival", keywords="fibroblast", keywords="protein", keywords="gastrointestinal", keywords="GI", keywords="gastrointestinal tumor", keywords="cancer", keywords="oncology", keywords="review method", keywords="systematic review", keywords="meta-analysis", keywords="meta-analyses", keywords="cell biology", keywords="proteomic", abstract="Background: A hallmark of gastrointestinal cancer, especially pancreatic cancer, is the dense stromal tumor microenvironment in which cancer-associated fibroblasts (CAFs) represent the major stromal cell type. Preclinical studies have demonstrated that depletion of fibroblast activation protein (FAP)--positive CAFs results in increased survival. Objective: We present the protocol for a systematic review and meta-analysis that aim to assess the currently available evidence on the effect of FAP expression on survival and clinical characteristics in gastrointestinal cancers. Methods: The literature search and data analysis will be conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 statement. The databases PubMed/MEDLINE, Web of Science Core Collection, Cochrane Library, and ClinicalTrials.gov will be searched via their respective online search engines. A meta-analysis comparing patients with and without FAP overexpression with the following outcomes will be performed: postoperative survival (overall and median survival; 1-, 2-, 3-, and 5-year survival rates), histological differentiation (grading), local tumor invasion, lymph node metastases, and distant metastases. Odds ratios will be calculated for binary data, and weighted mean differences and relative SD differences will be determined for continuous data. The 95\% CI, heterogeneity measures, and statistical significance will be reported for each outcome. The chi-square and Kruskal-Wallis tests will be used to evaluate statistical significance. A P value of <.05 will be considered statistically significant. Results: Database searches will commence in April 2023. The meta-analysis will be completed by December 2023. Conclusions: In recent years, several publications on FAP overexpression in gastrointestinal tumors have been published. The only published meta-analysis on this topic dates to 2015. It included 15 studies on various solid tumors and only 8 studies focusing exclusively on gastrointestinal tumors. The expected results of the present analysis will provide new evidence on the prognostic value of FAP in gastrointestinal tumors and thereby support health care professionals and patients in their decision-making. Trial Registration: PROSPERO CRD42022372194; https://tinyurl.com/352ae8b8 International Registered Report Identifier (IRRID): PRR1-10.2196/45176 ", doi="10.2196/45176", url="https://www.researchprotocols.org/2023/1/e45176", url="http://www.ncbi.nlm.nih.gov/pubmed/37099374" } @Article{info:doi/10.2196/34461, author="Moreira, In{\^e}s and Bartosch, Carla and Teixeira, Manuel and Ferreira, Marta", title="Molecular Classification of Endometrial Carcinoma: Protocol for a Cohort Study", journal="JMIR Res Protoc", year="2022", month="Aug", day="4", volume="11", number="8", pages="e34461", keywords="endometrial carcinoma", keywords="molecular classification", keywords="prognosis", keywords="POLE", keywords="mismatch repair", keywords="p53", abstract="Background: Endometrial carcinoma (EC) is the most common gynecologic malignancy in developed countries and the fourth most frequent in women worldwide. The cornerstone of treatment for EC is surgery. Clinicopathological features are currently used to help determine the individual risk of recurrence and the need for adjuvant treatment after surgery. Nonetheless, there is significant interobserver variability in assigning histologic subtype when using a morphological classification, revealing the need for a more unified approach. The Cancer Genome Atlas (TCGA) project identified 4 distinct prognostic EC subtypes based on genomic abnormalities. Surrogate assays including 3 immunohistochemical markers (p53, MSH6, and PMS2) and 1 molecular test (mutation analysis of the exonuclease domain of DNA polymerase epsilon; POLE) allowed the development and validation of a simplified molecular classifier that correlates with the TCGA classification, has prognostic value, and can easily be used in clinical practice. This molecular classification categorizes EC in 4 subtypes: POLE mutated, mismatch repair--deficient, p53 abnormal, and no specific molecular profile. Applying this classification in clinical practice will help tailor adjuvant treatment decisions. Objective: The aim of this study is to retrospectively apply this novel molecular classification to a cohort of patients with EC treated in a comprehensive cancer center, to assess its applicability in clinical practice, to evaluate clinical outcomes by molecular subtypes, and to assess its prognostic value. Methods: In this retrospective cohort study, patients with primary EC diagnosed during and after 2013 and treated or followed at our institution, after definite surgery, will be included. Demographic and clinicopathological data will be obtained from electronic health records and from pathology reports. Laboratory methods will include immunohistochemical study of p53 and mismatch repair proteins, as well as POLE mutational analysis by genetic sequencing. The primary end point is recurrence-free survival and secondary end points are disease-specific survival and overall survival. A descriptive analysis of variables will be carried out. Survival analysis will be performed using the Kaplan-Meier method and the groups will be compared using the log-rank test. Results: This protocol was reviewed and approved by the Instituto Portugu{\^e}s de Oncologia do Porto, Portugal, ethics committee in October 2021; patient selection from our cancer registry began the same month. A total of 160 patients will be included. This work will present real-life results that will allow a better understanding of the Portuguese EC population and the distribution of the molecular subgroups throughout. We will use these results to understand the prognostic value of this classification in our population and its role in adjuvant therapy decisions. This study is anticipated to conclude in December 2022. Conclusions: This study will provide important information regarding these women's outcomes according to this new molecular classification and will support its use when discussing a patient's need for adjuvant treatment. International Registered Report Identifier (IRRID): PRR1-10.2196/34461 ", doi="10.2196/34461", url="https://www.researchprotocols.org/2022/8/e34461", url="http://www.ncbi.nlm.nih.gov/pubmed/35925678" } @Article{info:doi/10.2196/31128, author="Shahzadi, Kiran Syeda and Karuvantevida, Noushad and Banerjee, Yajnavalka", title="A Venomics Approach to the Identification and Characterization of Bioactive Peptides From Animal Venoms for Colorectal Cancer Therapy: Protocol for a Proof-of-Concept Study", journal="JMIR Res Protoc", year="2021", month="Dec", day="21", volume="10", number="12", pages="e31128", keywords="animal venoms", keywords="colorectal cancer", keywords="bioactive peptides", keywords="high-throughput screening", keywords="venom", keywords="cancer", keywords="colorectal", keywords="peptide", keywords="screening", keywords="treatment", keywords="conceptual", keywords="characterize", keywords="development", keywords="therapy", abstract="Background: Cancer is the third leading cause of death in the United Arab Emirates (UAE), after cardiovascular diseases and accidents. In the UAE, colorectal cancer (CRC) is the first and fourth most common cancer in males and females, respectively. Several treatment modalities have been employed for cancer treatment, such as surgery, radiotherapy, chemotherapy, hormone replacement therapy, and immunotherapy. These treatment modalities often elicit adverse effects on normal cells, causing toxic side effects. To circumvent these toxicities, there has been an increased impetus towards the identification of alternate treatment strategies. Animal venoms are rich sources of pharmacologically active polypeptides and proteins. Objective: In this proof-of-concept study, we will apply a high-throughput venomics strategy to identify and characterize anticancer bioactive peptides (BAPs) from 20 different animal venoms, specifically targeting CRC. We chose to focus on CRC because it is one of the foremost health issues in the UAE. Methods: In the initial study, we will screen 2500 different peptides derived from 20 different animal venoms for anticancer activity specifically directed against 3 CRC cell lines and two control cell lines employing the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay for cytotoxicity. Of the 20 venoms, 3 that exhibit specific and potent anticancer activity directed against the 3 CRC cell lines will be selected; and from these 3 venoms, the specific peptides with anti-CRC activity will be isolated and characterized. Results: This study is at the protocol development stage only, and as such, no results are available. However, we have initiated the groundwork required to disseminate the proposed study, which includes culturing of colorectal cancer cell lines and preparation of venom screens. Conclusions: In summary, the proposed study will generate therapeutic leads to manage and treat one of the leading health issues in the UAE, namely, CRC. International Registered Report Identifier (IRRID): PRR1-10.2196/31128 ", doi="10.2196/31128", url="https://www.researchprotocols.org/2021/12/e31128", url="http://www.ncbi.nlm.nih.gov/pubmed/34932002" } @Article{info:doi/10.2196/24936, author="AlShehry, Faiez Nawal and Shanker, Raja and Zaidi, Ahmed Syed Ziauddin and AlGhmlas, Fahad and Motabi, Hussein Ibraheem and Iqbal, Shahid and Butt, Ali Ahmad and AlShehri, Hassan and Tailor, Khan Imran and Altaf, Yasir Syed and AlGhamdi, Mubarak and Marie, Mohammed and AlFayez, Mansour and Al Zahrani, Kamal and Dwaimah, Mohammed and Al-Halouli, Tahani and Al-Shakweer, Wafaa and AlShehery, Zaher Maied and Zaidi, Zia Abdul Rehman and Gill, Munawar Atta and Albtoosh, Mohammed Belal and Ahmed, Musab", title="Role of 18F-Fluorodeoxyglucose--Positron Emission Tomography/Computed Tomography Imaging in the Prediction of Prognosis in Patients With Indolent Lymphoma: Prospective Study", journal="JMIR Form Res", year="2021", month="Nov", day="12", volume="5", number="11", pages="e24936", keywords="positron emission tomography", keywords="lymphoma", keywords="prognosis", keywords="indolent lymphoma", keywords="SUVmax", keywords="Deauville criteria", abstract="Background: The role of fluorodeoxyglucose--positron emission tomography/computed tomography (FDG-PET/CT) in indolent lymphoma has been minimally studied. Objective: This study aims to assess the value of FDG-PET/CT in predicting the prognosis of indolent lymphoma. Methods: We prospectively recruited 42 patients with indolent lymphoma. A total of 2 patients were excluded, and 40 underwent baseline PET/CT and follow-up at various time points. A total of 9 patients were observed only, 7 received 4 doses of rituximab alone, and 24 received chemoimmunotherapy. Metabolic response on follow-up PET/CT was assessed using the maximum standardized uptake value (SUVmax) and Deauville criteria (DC). We aimed to obtain the best SUVmax and DC to predict optimal survival rates, risk stratification, and optimize therapeutic strategies. The mean follow-up from the initial diagnosis was 33.83 months. Results: SUVmax <4.35 at interim PET/CT provided the best discrimination, with a progression-free survival (PFS) of 100\% and a median survival time of 106.67 months compared with SUVmax ?4.35 (P=.04), which had a PFS of 43.8\% and a median survival time of 50.17 months. This cutoff was also valuable in predicting overall survival at baseline, that is, 100\% overall survival with baseline SUVmax <4.35, versus 58.4\% for SUVmax ?4.35 (P=.13). The overall survival of patients with a baseline DC score <3.0 was 100\%, with a median overall survival of 106.67 months. Conclusions: We demonstrated the utility of PET/CT in indolent lymphomas. SUVmax (<4.35 vs ?4.35) on interim PET/CT performed best in predicting PFS. ", doi="10.2196/24936", url="https://formative.jmir.org/2021/11/e24936", url="http://www.ncbi.nlm.nih.gov/pubmed/34508363" } @Article{info:doi/10.2196/33241, author="Dunaway, Spencer and Aggarwal, Pushkar and Shaughnessy, Cristin and Neltner, Scott", title="Surgical Surprise: Cutaneous Metastasis Presenting for Mohs Micrographic Surgery Without a Prior Diagnostic Biopsy", journal="JMIR Dermatol", year="2021", month="Nov", day="1", volume="4", number="2", pages="e33241", keywords="cutaneous metastasis", keywords="Mohs surgery", keywords="biopsy", keywords="micrographic surgery", keywords="dermatology", keywords="dermatologist", keywords="skin cancer", keywords="melanoma", doi="10.2196/33241", url="https://derma.jmir.org/2021/2/e33241", url="http://www.ncbi.nlm.nih.gov/pubmed/37632877" } @Article{info:doi/10.2196/31150, author="Alshammari, O. Fatemah O. F. and Al-saraireh, M. Yousef and Youssef, M. Ahmed M. and Al-Sarayra, M. Yahya and Alrawashdeh, Mohammad Hamzeh", title="Cytochrome P450 1B1 Overexpression in Cervical Cancers: Cross-sectional Study", journal="Interact J Med Res", year="2021", month="Oct", day="12", volume="10", number="4", pages="e31150", keywords="cancer", keywords="cervical cancer", keywords="cytochrome P450", keywords="cytochrome 1B1", keywords="immunohistochemistry", keywords="toxicity", keywords="therapies", keywords="molecular", keywords="tumor", keywords="cytochrome", keywords="cervix", abstract="Background: Current standard treatments for patients with recurrent cervical cancer are not very effective and are associated with severe toxicity. Recently, the rational approach for the discovery of new therapies for cervical cancer is based on the alterations in the molecular biology of cancer cells. One of the emerging molecular changes in cancer cells is the aberrant expression of cytochrome P450 1B1 (CYP1B1). This unique enzyme has been reported to be selectively overexpressed in several cancers. Objective: The aim of this study was to examine CYP1B1 expression in cervical cancers and to assess the enzyme's relationship with several clinicopathological features. Methods: Immunohistochemistry was performed to examine CYP1B1 expression in 100 patient samples with cervical cancer and 10 patient samples with normal healthy cervical tissues. Results: CYP1B1 was expressed in the majority of the cervical cancer samples (91/100, 91.0\%) but not in normal healthy cervical samples. The difference in the expression of CYP1B1 between healthy and tumorous cervical tissues was significant (P=.01). Moreover, the frequency of CYP1B1 expression was found to be significantly higher in patients with advanced grades of the disease (P=.03) and in patients having metastasis to the lymph nodes (P=.01). Surprisingly, there was a significantly higher expression of CYP1B1 in patients with a high prevalence of human papilloma virus 16/18 (P=.04). Conclusions: The differential profile of CYP1B1 expression between cervical cancer tissues and normal cervical tissues suggests that CYP1B1 may be used as a target for future therapeutic exploitations. ", doi="10.2196/31150", url="https://www.i-jmr.org/2021/4/e31150", url="http://www.ncbi.nlm.nih.gov/pubmed/34636736" } @Article{info:doi/10.2196/24423, author="Li, Guorong and Mallouk, Nora and Flandrin, Pascale and Garcin, Arnauld and Lambert, Claude and Berremila, Ali Sid and Habchi, Hocine and Mottet, Nicolas", title="Presence of Urinary Exosomes for Liquid Biopsy of Clear Cell Renal Cell Carcinoma: Protocol for a Pilot Feasibility Study", journal="JMIR Res Protoc", year="2021", month="Jul", day="20", volume="10", number="7", pages="e24423", keywords="liquid biopsy", keywords="urine exosome", keywords="CA9", keywords="clear cell renal cell carcinoma", keywords="kidney cancer", abstract="Background: Approximately 70\%-80\% of kidney cancers are clear cell renal cell carcinomas (CCRCCs). Patient management is based on imaging (abdominal ultrasound and computerized tomography), surgical excision of the tumor, and pathological analysis. A tissue biopsy is therefore necessary to confirm the diagnosis and avoid unnecessary nephrectomy. For metastatic cancers, a tissue biopsy is essential for establishing the targeted therapy. This biopsy of tumor material is invasive and painful. Other techniques such as liquid biopsy would help reduce the need for tissue biopsy. The development of a simple biological test for diagnosis is essential. CA9 is a powerful marker for the diagnosis of CCRCC. Exosomes have become a major source of liquid biopsy because they carry tumor proteins, RNA, and lipids. Urine is the most convenient biological liquid for exosome sampling. Objective: The aim of this study (PEP-C study) is mainly to determine whether it is possible to detect urinary exosomal CA9 for the molecular diagnosis of CCRCC. Methods: This study will include 60 patients with CCRCC and 40 noncancer patients. Exosomes will be isolated from urine samples and exosomal CA9 will be detected by transmission electron microscopy, flow cytometry, and reverse transcription-quantitative polymerase chain reaction. Results: This study is currently underway with funding support from the CHU Saint-Etienne of France. Conclusions: We expect to demonstrate that urinary tumor exosomes could be a novel liquid biopsy to diagnose CCRCC and to guide clinicians in treatment decision-making. Trial Registration: ClinicalTrials.gov NCT04053855; https://clinicaltrials.gov/ct2/show/NCT04053855 International Registered Report Identifier (IRRID): DERR1-10.2196/24423 ", doi="10.2196/24423", url="https://www.researchprotocols.org/2021/7/e24423", url="http://www.ncbi.nlm.nih.gov/pubmed/34283029" } @Article{info:doi/10.2196/16974, author="Giampietri, Claudia and Tomaipitinca, Luana and Scatozza, Francesca and Facchiano, Antonio", title="Expression of Genes Related to Lipid Handling and the Obesity Paradox in Melanoma: Database Analysis", journal="JMIR Cancer", year="2020", month="May", day="19", volume="6", number="1", pages="e16974", keywords="gene expression", keywords="obesity paradox", keywords="melanoma, colorectal cancer", keywords="CD36", keywords="FABPs", keywords="transcriptomic analysis", keywords="public databases", abstract="Background: Publicly available genomic and transcriptomic data in searchable databases allow researchers to investigate specific medical issues in thousands of patients. Many studies have highlighted the role lipids play in cancer initiation and progression and reported nutritional interventions aimed at improving prognosis and survival. Therefore, there is an increasing interest in the role that fat intake may play in cancer. It is known that there is a relationship between BMI and survival in patients with cancer, and that there is an association between a high-fat diet and increased cancer risk. In some cancers, such as colorectal cancer, obesity and high fat intake are known to increase the risk of cancer initiation and progression. On the contrary, in patients undergoing treatment for melanoma, a higher BMI unexpectedly acts as a protective factor rather than a risk factor; this phenomenon is known as the obesity paradox. Objective: We aimed to identify the molecular mechanism underlying the obesity paradox, with the expectation that this could indicate new effective strategies to reduce risk factors and improve protective approaches. Methods: In order to determine the genes potentially involved in this process, we investigated the expression values of lipid-related genes in patients with melanoma or colorectal cancer. We used available data from 2990 patients from 3 public databases (IST [In Silico Transcriptomics] Online, GEO [Gene Expression Omnibus], and Oncomine) in an analysis that involved 3 consecutive validation steps. Of this group, data from 1410 individuals were analyzed in the IST Online database (208 patients with melanoma and 147 healthy controls, as well as 991 patients with colorectal cancer and 64 healthy controls). In addition, 45 melanoma, 18 nevi, and 7 healthy skin biopsies were analyzed in another database, GEO, to validate the IST Online data. Finally, using the Oncomine database, 318 patients with melanoma (312 controls) and 435 patients with colorectal cancer (445 controls) were analyzed. Results: In the first and second database investigated (IST Online and GEO, respectively), patients with melanoma consistently showed significantly (P<.001) lower expression levels of 4 genes compared to healthy controls: CD36, MARCO, FABP4, and FABP7. This strong reduction was not observed in patients with colorectal cancer. An additional analysis was carried out on a DNA-TCGA data set from the Oncomine database, further validating CD36 and FABP4. Conclusions: The observed lower expression of genes such as CD36 and FABP4 in melanoma may reduce the cellular internalization of fat and therefore make patients with melanoma less sensitive to a high dietary fat intake, explaining in part the obesity paradox observed in patients with melanoma. ", doi="10.2196/16974", url="http://cancer.jmir.org/2020/1/e16974/", url="http://www.ncbi.nlm.nih.gov/pubmed/32209538" } @Article{info:doi/10.2196/14401, author="Tran, Xuan Bach and Latkin, A. Carl and Sharafeldin, Noha and Nguyen, Katherina and Vu, Thu Giang and Tam, S. Wilson W. and Cheung, Ngai-Man and Nguyen, Thi Huong Lan and Ho, H. Cyrus S. and Ho, M. Roger C.", title="Characterizing Artificial Intelligence Applications in Cancer Research: A Latent Dirichlet Allocation Analysis", journal="JMIR Med Inform", year="2019", month="Sep", day="15", volume="7", number="4", pages="e14401", keywords="scientometrics", keywords="cancer", keywords="artificial intelligence", keywords="global", keywords="mapping", abstract="Background: Artificial intelligence (AI)--based therapeutics, devices, and systems are vital innovations in cancer control; particularly, they allow for diagnosis, screening, precise estimation of survival, informing therapy selection, and scaling up treatment services in a timely manner. Objective: The aim of this study was to analyze the global trends, patterns, and development of interdisciplinary landscapes in AI and cancer research. Methods: An exploratory factor analysis was conducted to identify research domains emerging from abstract contents. The Jaccard similarity index was utilized to identify the most frequently co-occurring terms. Latent Dirichlet Allocation was used for classifying papers into corresponding topics. Results: From 1991 to 2018, the number of studies examining the application of AI in cancer care has grown to 3555 papers covering therapeutics, capacities, and factors associated with outcomes. Topics with the highest volume of publications include (1) machine learning, (2) comparative effectiveness evaluation of AI-assisted medical therapies, and (3) AI-based prediction. Noticeably, this classification has revealed topics examining the incremental effectiveness of AI applications, the quality of life, and functioning of patients receiving these innovations. The growing research productivity and expansion of multidisciplinary approaches are largely driven by machine learning, artificial neural networks, and AI in various clinical practices. Conclusions: The research landscapes show that the development of AI in cancer care is focused on not only improving prediction in cancer screening and AI-assisted therapeutics but also on improving other corresponding areas such as precision and personalized medicine and patient-reported outcomes. ", doi="10.2196/14401", url="https://medinform.jmir.org/2019/4/e14401", url="http://www.ncbi.nlm.nih.gov/pubmed/31573929" }