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Preprint ARTICLE | doi:10.20944/preprints202305.1971.v1

Potential Immunotherapy of Dendritic Cell-Cytokine-Induced Killer Cells for Refractory Metastatic Colorectal Cancer: A Preliminary Experience of Single Tertiary Hospital

Tao-Wei Ke, Cheng-Wei Huang, Sheng-Chi Chang, Wen-Liang Huang, Chin-Ting Hsu, Cheng-Kang Tsai, Chien-Lin Chen, Cheng-Li Lin, Hei-Tung Yip, Der-Yang Cho, Chang-Hai Tsai, William Tzu-Liang Chen, Woei-Cherng Shyu, Long-Bin Jeng

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: DC-CIK; immunotherapy; colorectal cancer

Online: 29 May 2023 (05:03:40 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202305.1968.v1

SaBrcada: Survival Intervals Prediction for Breast Cancer Patients by Dimension Raising and Age Stratification

Shih-Huan Lin, Ching-Hsuan Chien, Kai-Po Chang, Min-Fang Lu, Yu-Ting Chen, Yen-Wei Chu

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: breast cancer; deep learning; survival analysis; data dimension raising; age stratification

Online: 29 May 2023 (04:52:42 CEST)

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Preprint REVIEW | doi:10.20944/preprints202305.1937.v1

Prospective Clinical Trials to Advance the Study of Immunotherapy Toxicities

Christopher Cluxton, Jarushka Naidoo

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Cancer Immunotherapy; Tumour Immunology; Clinical trials; Adverse effects

Online: 26 May 2023 (14:16:17 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202305.1905.v1

A Novel Anti-CD44 Variant 10 Monoclonal Antibody is Useful for Immunohistochemical Analysis against Oral Squamous cell carcinomas

Kenichiro Ishikawa, Hiroyuki Suzuki, Mika K Kaneko, Yukinari Kato

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: CD44; CD44v10; monoclonal antibody; oral squamous cell carcinoma; immunohistochemistry

Online: 26 May 2023 (09:49:30 CEST)

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Preprint REVIEW | doi:10.20944/preprints202305.1877.v1

From Dual Roles to Translational Challenges: Unpacking the Complexities of Tumor-Associated Macrophages in Cancer Progression and Therapy

Shengwen Shao, HuiLai Miao, Wenxue Ma

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Tumor-associated macrophages (TAM); Tumor microenvironment (TME); Cytokine; Immunosuppression; Pro-tumor functions; Anti-tumor functions; Clinical application.

Online: 26 May 2023 (07:31:53 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202305.1804.v1

Targeting M2-TAM via STAT3/NF-kB/AKT Signaling Pathway With Oxaliplatin, Retinoic Acid, and Libidibia ferrea -Loaded Extracellular Vesicles From Macrophages 1 Down-Regulates Murine Colon Cancer Metastasis

Thaís Gomes De Carvalho, Pablo Lara, Carla Jorquera-Cordero, Timo Schomann, Cícero Flávio Soares Aragão, Artur de Santana Oliveira, Vinicius Barreto Garcia, Shirley Vitória de Paiva Souza, Isabelle de Lima Marques, Luiz Alberto Lira Soares, Paulo Marcos Da Matta Guedes, Raimundo Fernandes De Araújo-Júnior

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: EVs; Macrophages 1; STAT3, AKT; NF-κB; metastasis; colorectal cancer.

Online: 25 May 2023 (10:48:17 CEST)

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Despite the numerous advances in target therapy for the treatment of colorectal cancer, aggressive colorectal cancer remains an incurable disease whose negative modulation of the immune system in the tumor microenvironment is still critical for improving the patient's prognosis. Extracellular vesicles (EVs) have received attention for their use as cell-membrane-camouflaged nanoparticles and drug delivery systems in nanomedicine derived by nearly all cell types for intercellular communication and regulation in the tumor microenvironment (TME). In this study, M1 Macrophage EVs (M1EVs) were used as nanocarriers of oxaliplatin (M1EV1) associated with retinoic acid (M1EV2) and Libidibia ferrea (M1EV3), or combined together with retinoic acid and Libidibia ferrea (M1EV4) to evaluate their antiproliferative and immunomodulatory potential on CT-26 and MC-38 colorectal cancer cell lines, as well as their capacity to prevent metastases in mouse models of colorectal cancer such as allographic and peritoneal. Tumors were evaluated by qRT-PCR and immunohistochemistry. The cell death profile and epithelial-mesenchymal transition process (EMT) were analyzed in vitro in colorectal cancer cell lines. Polarization of murine macrophages (RAW264.7 cells) was also carried out. M1EV2 and M1EV3 used alone or especially combined (M1EV4) downregulated the tumor progression by TME immunomodulation, leading to a decrease in primary tumor size and metastases in peritoneum, liver and lungs. STAT3, NF-kB and AKT were the major genes downregulated by systems of M1EVs. Tumor-associated macrophages (TAM) switched M2 phenotype (CD163) towards M1 (CD68) reducing levels of IL-10, TGF-β and CCL22. Furthermore, malignant cells showed overexpression of FADD, APAF-1, caspase-3, and E-cadherin, and decreased expression of MDR-1, survivin, vimentin, CXCR4, and PD-L1 after treatment with systems of M1EVs. The results obtained in this study provided evidence that EVs from M1 antitumor macrophages can transport drugs and increase their immunomodulatory and antitumor activity by stimulating activation or blockage of pathways involved in cell proliferation, migration, cell survival, and drug resistance processes.

Preprint ARTICLE | doi:10.20944/preprints202305.1679.v1

Ferroptosis-Mediated Cell Death Induced by NCX4040, The Non-Steroidal Nitric Oxide Donor, in Human Colorectal Cancer Cells: Implications in Therapy

Birandra Kumar Sinha, Carl D Bortner, Alan K Jatmusch, Erik J Tokar, Carri Murphey, Xian Wu, Heather Winter, Ronald E Cannon

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Ferroptosis; NCX4040; Erastin; Ferrostatin-1; RSL3; Colon Cancer

Online: 24 May 2023 (03:52:22 CEST)

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Preprint COMMUNICATION | doi:10.20944/preprints202305.1667.v1

Liphedema Rehabilitation after Breast Cancer Surgery Using Combined Physiotherapy Techniques

Maria Baltag Oana, Mihaela Apostu, Kristo Xhardo, Daniel Andrei Iordan, Ilie Onu, Mariana Cordun

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: breast cancer; lymphedema management; manual lymph drainage; liphedema rehabilitation after mastectomy

Online: 24 May 2023 (02:11:14 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202305.1657.v1

Metabolic Dysregulation Explains the Diverse Impacts of Obesity in Males and Females with Gastrointestinal Cancers

Spencer R. Rosario, Bowen Dong, Yali Zhang, Hua-Hsin Hsiao, Emily Isenhart, Jianmin Wang, Erin M. Siegel, Arta Monir Monjazeb, Dwight H. Owen, Prasenjit Dey, Fred K. Tabung, Daniel Spakowicz, William J. Murphy, Stephen B. Edge, Sai Yendamuri, Sami Ibrahimi, Jill M. Kolesar, Patsy H. McDonald, Deepak Vadehra, Michelle Churchman, Song Liu, Pawel Kalinsky, Sarbajit Mukherjee

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: obesity; gender; metabolism; cancer; gastrointestinal

Online: 23 May 2023 (12:43:10 CEST)

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Background: The prevalence of obesity, defined as body mass index (BMI) ≥ 30 kg/m2, has reached epidemic levels. Obesity is associated with an increased risk of various cancers, including gastrointestinal ones. Recent evidence has suggested that obesity disproportionately impacts males and females with cancer, resulting in varied transcriptional and metabolic dysregulation. Methods: This study aimed to elucidate the differences in the metabolic milieu of adenocarcinomas of the gastrointestinal (GI) track both related and unrelated to sex in obesity. To demonstrate these obesity and sex-related effects, we utilized three primary data sources: serum metabolomics from obese and non-obese patients assessed via the Biocrates MxP Quant 500 mass spectrometry-based kit, the ORIEN tumor RNA-sequencing data for all adenocarcinoma cases to assess the impacts of obesity, and publicly available TCGA transcriptional analysis to assess GI cancers and sex-related differences in GI cancers specifically. We applied and integrated our unique transcriptional metabolic pipeline in combination with our metabolomics data to reveal how obesity and sex can dictate differential metabolism in patients. Results: Differentially expressed genes (DEG) analysis of ORIEN obese adenocarcinoma as compared to normal-weight adenocarcinoma patients resulted in large-scale transcriptional reprogramming (4029 DEGs, adj. p < 0.05 and |logFC|>0.58). Gene Set Enrichment and metabolic pipeline analysis showed genes enriched for pathways relating to immunity (inflammation, and CD40 signaling, among others) and metabolism. Specifically, we found alterations to steroid metabolism and tryptophan/kynurenine metabolism in obese patients, both of which are highly associated with disease severity and immune cell dysfunction. These findings were further confirmed using the TCGA colorectal adenocarcinoma (CRC) and esophageal adenocarcinoma (ESCA) data, which showed similar patterns of increased tryptophan catabolism for kynurenine production in obese patients. These patients further showed disparate alterations between males and females when comparing obese to non-obese patient populations. Alterations to immune and metabolic pathways were validated in 6 patients (2 obese and 4 normal weight) via CD8+/CD4+ peripheral blood mononuclear cell RNA-sequencing and paired serum metabolomics, which showed differential kynurenine and lipid metabolism, which corresponded with altered T-cell transcriptome in obese populations. Conclusions: Overall, obesity is associated with differential transcriptional and metabolic program in various disease sites. Further, these alterations, like kynurenine and tryptophan metabolism, which impact both metabolism and immune phenotype, vary with sex and obesity together. This study warrants further in-depth investigation into obesity and sex-related alterations in cancers that may better define biomarkers of response to immunotherapy.

Preprint REVIEW | doi:10.20944/preprints202305.1646.v1

The Exploitation of Lysosomes in Cancer Therapy with Graphene-Based Nanomaterials

Biljana Ristic, Mihajlo Bosnjak, Maja Misirkic Marjanovic, Danijela Stevanovic, Kristina Janjetovic, Ljubica Harhaji-Trajkovic

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: graphene-based nanomaterials; graphene-based drug delivery systems; lysosomes; cancer; endosomal/lysosomal escape; lysosomal cell death

Online: 23 May 2023 (10:52:24 CEST)

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Preprint REVIEW | doi:10.20944/preprints202305.1637.v1

Computational Advancements in Drug Repurposing for Cancer Combination Therapy Prediction

Victoria L. Flanary, Jennifer L. Fisher, Elizabeth J. Wilk, Timothy C. Howton, Brittany N. Lasseigne

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: computational; drug repurposing; drug repositioning; cancer; combination therapy; network biology; machine learning; deep learning; precision oncology

Online: 23 May 2023 (10:19:47 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202204.0132.v2

Sentinel Lymph Node in Breast Cancer: An Innovative Technique Innovation in Breast Cancer

Paolo Izzo, Claudia De Intinis, Simone Sibio, Luigi Basso, Andrea Polistena, Gabriele Raimondo, Massimo Codacci-Pisanelli, Luciano Izzo, Sara Izzo

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: SLNB; SPIO; ALND; LS; superparamagnetic iron oxide nanoparticles

Online: 23 May 2023 (05:26:30 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202305.1576.v1

Potential Utility of a Panel of Four-miRNAs As Biomarkers in the Clinical Management of Obese and Non-obese Colorectal Cancer Patients

Sofía Elena Tesolato, Daniel González-Gamo, Ana Barabash, Paula Claver, Sofía Cristina De la Serna, Inmaculada Domínguez-Serrano, Jana Dziakova, Carmen De Juan, Antonio José Torres, Pilar Iniesta

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: colorectal cancer; adipose tissue; miRNAs; serum biomarkers; obesity

Online: 23 May 2023 (05:03:00 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202305.1572.v1

The Prognostic Nutritional Index (PNI): A New Biomarker for Determining Prognosis in Metastatic Castration-Sensitive Prostate Carcinoma

Halil İbrahim Ellez, Merve Keskinkilic, Huseyin Salih Semiz, Mehmet Emin Arayici, Erdem Kısa, Ilhan Oztop

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: prostate cancer; prognostic nutritional index; inflammation; prognosis

Online: 23 May 2023 (04:50:23 CEST)

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Preprint REVIEW | doi:10.20944/preprints202305.1503.v1

Exosomes Analysis in Prostate Cancer: How They Can Improve Biomarkers Performance

Stefano Salciccia, Marco Frisenda, Giulio Bevilacqua, Luca Gobbi, Bruno Bucca, Martina Moriconi, Pietro Viscuso, Alessandro Gentilucci, Gianna Mariotti, Susanna Cattarino, Flavio Forte, Stefano Fais, Mariantonia Logozzi, Beatrice Sciarra, Alessandro Sciarra

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: exosome; prostate cancer; biomarker

Online: 22 May 2023 (10:39:32 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202305.1499.v1

Chemoradiation with Cisplatin vs. Carboplatin for Squamous Cell Carcinoma of the Head-and-Neck (SCCHN)

Dirk Rades, Inga Zwaan, Tamer Soror, Christian Idel, Ralph Pries, Karl L Bruchhage, Samer G. Hakim, Nathan Y. Yu

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: head-and-neck cancer; chemoradiation; cisplatin; carboplatin; loco-regional control; metasta-ses-free survival; overall survival; toxicity

Online: 22 May 2023 (10:21:54 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202305.1470.v1

Lessons from a 3-Year Review of PSMA PET-CT in a Tertiary Setting: Can We Fine Tune Referral Criteria by Identifying Factors Predicting Positivity and Negativity?

Vineet Pant, Sobhan Vinjamuri, Ahmad zaid Zanial, Faisal Naeem

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: PSMA PET CT; Biochemical Recurrence; prostate cancer recurrence; prostate bed recurrence

Online: 22 May 2023 (07:25:45 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202305.1353.v1

Mutations in the PIK3C2B, ERBB3, KIT, and MLH1 Genes and their Relationship with Resistance to Temozolomide in Patients with High-grade Gliomas

León Darío Ortiz Gómez, Heidy Johanna Contreras Martínez, Piedad Matilde Agudelo Florez, David Andrés Galvis Pareja, Ronald guillermo Pelaez

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: gliomas; temozolomide; resistance; genes; PIK3C2B; ERBB3; KIT; MLH1; MGMT

Online: 18 May 2023 (14:59:42 CEST)

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Preprint REVIEW | doi:10.20944/preprints202305.1305.v1

Heat Shock Proteins Mediate Intercellular Communications within Tumor Microenvironment Cells through Extracellular Vesicles

Renata F. Saito, Maria Cristina Rangel, Andreia Hanada Otake, Camila Maria Longo Machado

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Heat-shock-protein; extracellular vesicles; reprograming tumors; tumor evolucionary pressure

Online: 18 May 2023 (08:46:07 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202305.1285.v1

Characteristics of Phase IV Clinical Trials in Oncology: An Analysis Using the ClinicalTrials.gov Registry Data

Brandon Michael Henry, Giuseppe Lippi, Ameen Nasser, Patryk Ostrowski

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: postmarketing surveillance; pharmacovigilance; registry data

Online: 18 May 2023 (07:18:52 CEST)

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Preprint REVIEW | doi:10.20944/preprints202305.1239.v1

Immune Checkpoint Blockade and Biomarkers of Response in Lymphoma: A Case-Illustrated Narrative Review

Sarah Perdikis-Prati, Semira Sheikh, Bouroumeau Antonin, Noémie Lang

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Hodgkin lymphoma; non-Hodgkin lymphoma; PD1 / PD-L1 checkpoint inhibitors; tumor mutational burden; predictive biomarkers

Online: 17 May 2023 (10:52:16 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202305.1126.v1

High Expression of MRE11A, the Gene Involved in the Resection Step During Homologous Recombination, Is Associated with Shorter Survival and a Higher Risk of Death in CRC Patients

Daniel de Barcelos Azambuja, Helena de Castro E Glória, Gabriel e Silva Montenegro, Antonio Nocchi Kalil, Jean-Sébastien Hoffmann, Natalia Leguisamo, Jenifer Saffi

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: colorectal cancer; homologous recombination; prognosis; Mre11

Online: 16 May 2023 (08:30:40 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202305.0995.v1

Development of a Novel Anti-CD44 Variant 8 Monoclonal Antibody C₄₄Mab-94 against Gastric Carcinomas

Hiroyuki Suzuki, Nohara Goto, Tomohiro Tanaka, Tsunenori Ouchida, Mika K. Kaneko, Yukinari Kato

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: CD44 variant 8; monoclonal antibody; gastric cancer; flow cytometry; immunohistochemistry

Online: 15 May 2023 (07:41:36 CEST)

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Preprint REVIEW | doi:10.20944/preprints202305.0967.v1

Recent Insight About HE4 Role in Ovarian Cancer Oncogenesis

Emanuela Anastasi, Antonella Farina, Teresa Granato, Flavia Colaiacovo, Beatrice Pucci, Sara Tartaglione, Antonio Angeloni

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Ovarian cancer; HE4; oncogenesis; target therapy

Online: 15 May 2023 (03:19:07 CEST)

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Preprint REVIEW | doi:10.20944/preprints202305.0914.v1

KRAS-dependency in Pancreatic Ductal Adenocarcinoma: Mechanisms of Escaping in Resistance to KRAS Inhibitors

Enrico Gurreri, Giannicola Genovese, Luigi Perelli, Antonio Agostini, Geny Piro, Carmine Carbone, Giampaolo Tortora

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: pancreatic cancer; KRAS; KRAS inhibitors; KRAS-dependency; resistance; escaping.

Online: 12 May 2023 (09:33:30 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202305.0912.v1

Application of Spectral Algorithm Applied to Spatially Registered Bi-Parametric MRI to Predict Tumor Aggressiveness: A Pilot Study

Rulon Mayer, Baris Turkbey, Peter L. Choyke, Charles Simone II

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: logistic probability; prostate cancer; bi-parametric magnetic resonance imaging (BP-MRI); Gleason score (GS); signal-to-clutter ratio (SCR); regularization

Online: 12 May 2023 (09:06:16 CEST)

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Background: Current prostate cancer evaluation can be inaccurate and burdensome. Quantitative evaluation of MRI sequences non-invasively helps prostate tumor assessment. However, including Dynamic Contrast Enhancement in the examined MRI sequence set can add complications, inducing possible side effects from the IV placement or injected contrast material, and prolongs scanning time. Purpose: Predict the risk of developing Clinically Significant (Insignificant) prostate cancer CsPCa (CiPCa) and International Society of Urologic Pathology (ISUP) grade using processed Signal to Clutter Ratio (SCR) derived from spatially registered bi-parametric MRI (SRBP-MRI) and thereby enhance non-invasively management of prostate cancer. Methods: This pilot study retrospectively analyzed 42 consecutive prostate cancer patients from the PI-CAI data collection. BP-MRI (Apparent Diffusion Coefficient, High B-value, T2) were resized, translated, cropped, and stitched to form spatially registered SRBP-MRI. Efficacy of noise reduction was tested by regularizing, eliminating principal components (PC), and minimizing elliptical volume from the covariance matrix to optimize the SCR. MRI guided biopsy (MRBx), Systematic Biopsy (SysBx), combination (MRBx+SysBx), or radical prostatectomy determined the ISUP grade for each patient. ISUP grade >=2 (<2) was judged as CsPCa (CiPCa). Linear and Logistic regression were fitted to ISUP grade and CsPCa/CiPCa SCR. Correlation Coefficients (R) and Area Under the Curves (AUC) for Receiver Operator Curves (ROC) evaluated the performance. Results: High correlation coefficients (R) (>0.55) and high AUC (=1.0) for linear and/or logistic fit from processed SCR and z-score for SRBP-MRI greatly exceed fits using prostate serum antigen, prostate volume, and patient age (R~0.17). Patients assessed with combined MRBx+SysBx and from individual MRI scanners achieved higher R (R=0.207+/-0.118) than using all patients in the fits. Conclusions: In the first study to date to apply and test hyperspectral approaches for assessing tumor aggressiveness on SRBP-MRI, high values of R and exceptional AUC to fit the ISUP grade and CsPCA/CiPCA were comparable or better than those from artificial intelligence in other studies.

Preprint REVIEW | doi:10.20944/preprints202305.0801.v1

Pet Radiomics and Response to Immunotherapy in Lung Cancer: A Systematic Review of the Literature

Laura Evangelista, Francesco Fiz, Riccardo Laudicella, Francesco Bianconi, Angelo Castello, Priscilla Guglielmo, Virginia Liberini, Luigi Manco, Viviana Frantellizi, Alessia Giordano, Luca Urso, Stefano Panareo, Barbara Palumbo, Luca Filippi

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: immunotherapy; lung cancer; PET; response to therapy; PD-L1

Online: 11 May 2023 (05:32:06 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202305.0705.v1

Contrast-enhanced Liver MR Synthesis using Gradient Regularized Multi-Modal Multi-Discrimination Sparse Attention Fusion GAN

Changzhe Jiao, Diane Ling, Shelly Bian, April Vassantachart, Karen Cheng, Shahil Mehta, Derrick Lock, Zhenyu Zhu, Mary Feng, Horatio Thomas, Jessica E Scholey, Ke Sheng, Zhaoyang Fan, Wensha Yang

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: MR synthesis, GAN, multi-modal fusion, tumor monitoring, contrast enhancement

Online: 10 May 2023 (08:10:11 CEST)

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Purposes: To provide abdominal contrast-enhanced MR image synthesis, we developed an image gradient regularized multi-modal multi-discrimination sparse-attention fusion generative adversarial network (GRMM-GAN) to avoid repeated contrast injections to patients and facilitate adaptive monitoring. Methods: With IRB approval, 165 abdominal MR studies from 61 liver cancer patients were retrospectively solicited from our institutional database. Each study included T2, T1 pre-contrast (T1pre), and T1 contrast-enhanced (T1ce) images. The GRMM-GAN synthesis pipeline consists of a sparse attention fusion network, an image gradient regularizer (GR), and a generative adversarial network with multi-discrimination. The studies were randomly divided into 115 for training, 20 for validation, and 30 for testing. The two pre-contrast MR modalities, T2 and T1pre images, were adopted as inputs in the training phase. The T1ce image at the portal venous phase was used as an output. The synthesized T1ce images were compared with the ground truth T1ce images. The evaluation metrics include peak signal-to-noise ratio (PSNR), structural-similarity-index (SSIM), and mean-squared-error (MSE). A Turing test and experts’ contours evaluated the image synthesis quality. Results: The proposed GRMM-GAN model achieved a PSNR of 28.56, an SSIM of 0.869, and an MSE of 83.27. The proposed model showed statistically significant improvements in all metrics tested with p-values <0.05 over the state-of-the-art model comparisons. The average Turing test score was 52.33%, close to random guessing, supporting the model's effectiveness for clinical application. In the tumor-specific region analysis, the average tumor contrast-to-noise ratio (CNR) of the synthesized MR images was not statistically significant from the real MR images. The average DICE from real vs. synthetic images was 0.90, compared to the inter-operator DICE of 0.91. Conclusion: We demonstrated the function of a novel multi-modal MR image synthesis neural network, GRMM-GAN, for T1ce MR synthesis based on pre-contrast T1 and T2 MR images. GRMM-GAN shows promise for avoiding repeated contrast injections during radiation therapy treatment.

Preprint COMMUNICATION | doi:10.20944/preprints202305.0641.v1

EMab-300 Detects Mouse Epidermal Growth Factor Receptor-Expressing Cancer Cell Lines in Flow Cytometry

Nohara Goto, Hiroyuki Suzuki, Tomohiro Tanaka, Kenichiro Ishikawa, Tsunenori Ouchida, Mika K. Kaneko, Yukinari Kato

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: mouse EGFR; monoclonal antibody; Cell-Based Immunization and Screening; CBIS

Online: 9 May 2023 (10:42:31 CEST)

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Preprint REVIEW | doi:10.20944/preprints202305.0620.v1

Acute Lymphoblastic Leukemia Immunotherapy Treatment: Now, Next, and Beyond

Anna Aureli, Beatrice Marziani, Adriano Venditti, Tommaso Sconocchia, Giuseppe Sconocchia

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: ALL; immunotherapy; antibody-drug conjugate; CAR-based therapies, targeted therapies

Online: 9 May 2023 (09:03:11 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202305.0561.v1

Immunotherapy with PD-1 Inhibitor Nivolumab in Recurrent/Metastatic Platinum Refractory Head and Neck Cancers: The Early Experience of Two Academic Center

Camil Ciprian Mireștean, Mihai Cosmin Stan, Michael Schenker, Constantin Volovăț, Simona Ruxandra Volovăț, Dragoș Petru Teodor Iancu, Roxana Irina Iancu, Badulescu Florinel

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Nivolumab; immunotherapy; head and neck cancers; HNSCC; chemotherapy; neutrophil to lymphocyt ratio; NLR; second primary malignancy; Cetuximab

Online: 9 May 2023 (04:21:38 CEST)

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The prognosis of patients with recurrent or metastatic of the head and neck squamous-cell carcinoma (HNSCC) refractory to platinum-based chemotherapy is severe and, consequently, the identification of therapeutic options for this category of patients is a priority. Nivolumab, an anti- programmed cell death protein 1 (anti-PD-1) monoclonal antibody, has been approved for the treatment of recurrent or metastatic HNSCC after platinum-based therapy progressing. We present the early experience of two academic center including diagnostic, clinical, biological, therapeutic and outcomes characteristics of head and neck cancer (HNC) patients treated with Nivolumab. The purpose of the study is to identify certain peculiarities and to report them compared to the data from the literature in order to generate some hypotheses that coud constitute criteria for the selection of cases with maximum benefit to immunotherapy. Analyzing the data obtained from 18 patients treated in Emergency County Hospital Craiova, "Saint Nectarie" Oncological Hospital Craiova and Euroclinic Oncological Center Iasi January 2020 and March 2023 it could be hypothesized that lower nadir values of neutrophil to lymphocyte ratio (<3.5) and the adition of intensive regimens of chemotherapy and radiotherapy could justify a favorable response in terms of progression free survival (PFS) during immunotherapy with Nivolumab. To our knowledge, the study included the first two cases of second primary malignancy (SPM) in the head neck region treated with Nivolumab. The reported data support a possible benefit of the sequential administration of radiotherapy, immunotherapy for SPM cases. Higher positive dynamic of neutrophil to lymphocyt ratio (NLR) could be associated with worst outcome during immunotherapy. All study observations including the role of infections and antibiotic treatment as well as the possible biomarker value of NLR variation during immunotherapy should be investigated in multicenter clinical trials.

Preprint ARTICLE | doi:10.20944/preprints202305.0530.v1

Characterization and Optimization of Multiomic Single-Cell Epigenomic Profiling

Leticia Sandoval, Wazim Mohammed Ismail, Amelia Mazzone, Mihai Dumbrava, Jenna Fernandez, Amik Munankarmy, Terra Lasho, Mortiz Binder, Vernadette Simon, Kwan Hyun Kim, Nicholas Chia, Jeong Heon Lee, S. John Weroha, Mrinal M. Patnaik, Alexandre Gaspar-Maia

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: single-cell sequencing; epigenomic profiling; snATAC-seq; snRNA-seq; nuclei preparation

Online: 8 May 2023 (11:00:52 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202305.0485.v1

Externally Applied Electromagnetic Fields and Hyperthermia Irreversibly Damage Cancer Cells

Elena Obrador, Ali Jihad-Jebbar, Rosario Salvador-Palmer, Rafael López-Blanch, María Oriol-Caballo, María Paz Moreno-Murciano, Enrique Navarro, Rosa Cibrian, José M. Estrela

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Non-ionizing radiations; Electromagnetic fields; Hyperthermia; Cancer therapy; Cancer cell death

Online: 8 May 2023 (08:53:59 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202305.0400.v1

In Vitro and In Vivo Efficacy of a Stroma Targeted, Tumor Microenvironment Responsive Oncolytic Adenovirus in Different Preclinical Models of Cancer

Ana Alfano, Eduardo G. A Cafferata, Mariela Gangemi, Alejandro Nicola Candia, Cristian M Malnero, Ismael Bermudez, Gregorio David Rios, Cecilia Rotondaro, Nicasio Cuneo, David T Curiel, Osvaldo L Podhajcer, Maria Veronica Lopez

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: transcriptionally targeted oncolytic adenovirus; gynecologic cancer; human samples; cytokines; ovarian cancer; tumor stroma

Online: 6 May 2023 (09:25:49 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202305.0284.v1

Evaluation of Contrast-Enhanced Mammography and Development of Flowchart for BI-RADS Classification of Breast Lesions

Kristina Klarić, Andrej Šribar, Anuška Budisavljević, Loredana Labinac Peteh, Petra Valković Zujić

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: breast cancer; contrast-enhanced mammography; magnetic resonance imaging

Online: 5 May 2023 (03:26:25 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202305.0173.v1

Expression of Immune Checkpoint Markers PD-1, PD-L1, CD8, MSI, and p53 in Advanced Serous Ovarian Carcinoma

Ana Paula Dergham, Seigo Nagashima, Caroline Busatta Vaz de Paula, Marcia Olandoski, Lucia De Noronha, Vanessa Santos Sotomaior

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: biomarkers; immunotherapy markers; advanced serous ovarian carcinoma; immunohistochemistry; p53; MSI

Online: 4 May 2023 (03:39:48 CEST)

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Preprint CASE REPORT | doi:10.20944/preprints202305.0157.v1

Invasion of Chronic Lymphocytic Leukemia ( CLL/SLL) Bloodstream Tumor Cells by Borrelia spirochetes

Alan Bruce MacDonald

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Borrelia infection; Leukemia; burgdorferi; Miyamotoi

Online: 3 May 2023 (13:07:25 CEST)

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Preprint REVIEW | doi:10.20944/preprints202305.0122.v1

Overview on Therapeutic Options in Uncommon EGFR Mutant Non-Small Cell Lung Cancer (NSCLC): New Lights for an Unmet Medical Need

Giulia Pretelli, Calogera Claudia Spagnolo, Giuliana Ciappina, Mariacarmela Santarpia, Giulia Pasello

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Non-small cell lung cancer (NSCLC); EGFR; Tyrosine kinase inhibitors (TKIs); Uncommon mutation; Compound mutation; Intracranial activity; Immunotherapy

Online: 3 May 2023 (09:29:08 CEST)

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Preprint REVIEW | doi:10.20944/preprints202304.1239.v1

In-silico Molecular Docking and Bibliometric Analyses of Dyes Used in Photodynamic Therapy in Cervical Cancer

Nasrulla Abdullaevich Shanazarov, Afshin Zare, Nadiar Maratovich Mussin, Rustam Kuanyshbekovich Albayev, Asset Askerovich Kaliyev, Yerbolat Maratovich Iztleuov, Sandugash Bakhytbekovna Smailova, Farhad Rahmanifar, Nazanin Jafari, Hanieh Baneshi, Amin Tamadon

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Cervical cancer; Human papillomavirus (HPV); Photodynamic therapy (PDT); Squamous in-traepithelial neoplasia; Bibliometric analysis; Molecular Docking; Fullerene

Online: 30 April 2023 (02:31:30 CEST)

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Preprint REVIEW | doi:10.20944/preprints202304.1185.v1

Chasing Circulating Biomarkers in Renal Cell Carcinoma: the Case of Extracellular Vesicles and their miRNA Cargos

Ilenia Mastrolia, Virginia Catani, Marco Oltrecolli, Stefania Pipitone, Maria Giuseppa Vitale, Valentina Masciale, Chiara Chiavelli, Carlo Augusto Bortolotti, Cecilia Nasso, Giulia Grisendi, Roberto Sabbatini, Massimo Dominici

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: renal cell carcinoma; liquid biopsy; blood; extracellular vesicles; microRNA; biomarker; diagnostics; prognosis; prediction

Online: 28 April 2023 (13:00:31 CEST)

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Preprint REVIEW | doi:10.20944/preprints202304.0901.v1

Combined Therapies with Taxanes Based-Chemotherapeutic Drugs in Prostate Cancer: Novel Insights and Future Directions

Rafaella S Coelho, Sandra M Rocha, Cláudio J Maia

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: PCa; taxanes-based drugs; combination therapy; transmembrane proteins

Online: 25 April 2023 (08:34:03 CEST)

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Preprint COMMUNICATION | doi:10.20944/preprints202304.0892.v1

The Implication of ATP Scavenging Behaviour and Upregulation of Immune Regulatory Receptor by Intracellular Porphyromonas gingivalis Based on In-Vitro Models on the Prognosis of Digestive Tract Cancers Regarding the Oral Cancer Patients

Manosha Perera, Irosha Perera

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Porphyromonas gingivalis; ATP scavenging behavior; Microbiome Medicine; Digestive tract cancers

Online: 25 April 2023 (07:05:39 CEST)

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Preprint REVIEW | doi:10.20944/preprints202304.0746.v2

Prognostic Factors for Cardiotoxicity Among Children With Cancer: Definition, Causes and Diagnosis With Omics Technologies

Kondylia Antoniadi, Nikolaos S. Thomaidis, Petros Nihoyannopoulos, Konstantinos Toutouzas, Evagelos Gikas, Charikleia Kelaidi, Sophia Polychronopoulou

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: cardiotoxicity, childhood cancer, chemotherapeutics agents, biomarkers, omics technology

Online: 24 April 2023 (04:06:08 CEST)

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Preprint REVIEW | doi:10.20944/preprints202304.0746.v1

Prognostic Factors for Cardiotoxicity Among Children With Can-Cer: Definition, Causes and Diagnosis With Omics Technologies

Kondylia Antoniadi, Nikolaos S. Thomaidis, Petros Nihoyannopoulos, Konstantinos Toutouzas, Evagelos Gikas, Charikleia Kelaidi, Sophia Polychronopoulou

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: cardiotoxicity, childhood cancer, chemotherapeutics agents, biomarkers, omics technology

Online: 23 April 2023 (03:36:10 CEST)

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Preprint REVIEW | doi:10.20944/preprints202304.0736.v1

Biological Therapies Beyond PARP-Inhibitors in Advanced Breast Cancer Patients with Germline BRCA1/2 Mutations

Marta Nerone, Lorenzo Rossi, Rosaria Condorelli, Vilma Ratti, Fabio Conforti, Antonella Palazzo, Rossella Graffeo

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: advanced breast cancer; germline BRCA1/2 mutations; pathogenic/likely pathogenic variants; CDK4/6 inhibitors; Pi3Ka inhibitors; HER2-low

Online: 23 April 2023 (03:12:48 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202304.0668.v1

Quality-Of-Life Survey of Pancreatic Cancer Patients: A Comparison Between General Public and Physicians

Yuriko Sasahara, Yuki Takumoto, Kaname Watanabe, Hiroyuki Takeda, Kumiko Umemoto, Yu Sunakawa, Naoki Suzuki, Takashi Yoshioka, Satoshi Kobayashi, Makoto Ueno, Sho Nakamura, Manabu Akazawa, Hiroto Narimatsu

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Quality-of-life; pancreatic cancer, physicians; VAS; cTTO; EQ-5D

Online: 21 April 2023 (03:51:46 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202304.0530.v1

PARP1: New Drug Development Opportunities for an Old Target

Pablo Iglesias, Marcos Seoane, Irene Golán-Cancela, Maximo Fraga, Víctor M. Arce, Jose A. Costoya

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Poly (ADP-Ribose) Polymerase-1; PARP inhibitors; neoplasm; cancer; animal disease models

Online: 19 April 2023 (03:30:59 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202304.0477.v1

Transplanting Heterologous Mitochondria from Human Umbilical Vein Endothelial Cells Reduces the Malignancy of Melanoma Cells

Fu-Chen Kuo, Bi-Ling Cheng, Ching-Chung Tsai, Ping-Chen Chen, Hsin-Yi Tsai, Kuen-Jang Tsai, Yaw-Bin Huang, Chung-Jung Liu, Deng-Chyang Wu, Ming-Wei Lin, Bin Huang

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Mitochondrial transplantation; Mitophagy; HUVEC; melanoma; EMT; malignancy

Online: 18 April 2023 (04:10:03 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202304.0452.v1

A Novel Anti-CD44 Variant 3 Monoclonal Antibody C44Mab-6 was Established for Multiple Applications

Hiroyuki Suzuki, Kaishi Kitamura, Nohara Goto, Kenichiro Ishikawa, Tsunenori Ouchida, Tomohiro Tanaka, Mika K. Kaneko, Yukinari Kato

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: CD44; CD44 variant 3; monoclonal antibody; flow cytometry; immunohistochemistry

Online: 17 April 2023 (10:44:35 CEST)

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Preprint REVIEW | doi:10.20944/preprints202304.0340.v1

Unraveling the Hidden Impact of Tumor Microenvironment: Insights into Novel Therapeutic Strategies for Oncology in Tanzania: Integrated Review

Samson Peter Mvandal, Wende Mlonganile

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Africa; cancer; immunotherapy; oncology; Tanzania; therapeutic; tumor microenvironment

Online: 14 April 2023 (03:30:46 CEST)

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The tumor microenvironment (TME) plays a critical role in cancer progression and treatment outcomes. Despite advances in cancer research, many therapeutic strategies have failed to provide the desired clinical outcomes. In this integrated review, aimed to explore the role of TME in cancer biology and develop novel therapeutic strategies that target not only cancer cells but also the surrounding microenvironment. Study conducted a comprehensive literature search using PubMed, Embase, and Web of Science databases for articles published between 2016 and 2022. Inclusion of articles that discussed the impact of TME on cancer development and progression, as well as articles that proposed novel therapeutic strategies targeting the TME. The analysis of the literature revealed that the TME plays a crucial role in cancer development and progression by promoting cancer cell survival, angiogenesis, invasion, and metastasis, and by interfering with the efficacy of cancer therapies. The TME is composed of a complex network of non-cancerous cells, extracellular matrix components, and signaling molecules that interact with cancer cells. Several novel therapeutic strategies have been proposed based on the modulation of TME components. One of the most promising approaches is the use of immunotherapy, which aims to enhance the immune system's ability to recognize and attack cancer cells. Immunotherapy drugs such as checkpoint inhibitors, chimeric antigen receptor (CAR) T cells, and immune-stimulatory monoclonal antibodies have been approved for the treatment of different cancer types. These approaches have shown promising results in preclinical studies and clinical trials. The TME plays a critical role in cancer development and progression, and targeting its components represents a promising avenue for cancer therapy. Novel therapeutic strategies such as immunotherapy, extracellular matrix-targeting drugs, and nanoparticle-based therapies have shown promising results in preclinical studies and clinical trials. However, further research is needed to identify the most effective strategies and to overcome the challenges associated with TME targeting.

Preprint ARTICLE | doi:10.20944/preprints202304.0253.v2

The Purpose of Adrenarche Is Tumor Suppression: Identification of a Novel, Human-Specific, Kill-Switch Tumor Suppression Mechanism Dependent upon the Dramatic Adrenarchal Rise of Adrenal Androgens

Jonathan Wesley Nyce

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: p53; adrenarche; dehydroepiandrosterone; DHEA; DHEAS

Online: 13 April 2023 (05:01:41 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202304.0253.v1

The Purpose of Adrenarche Is Tumor Suppression: Identification of a Novel, Human-Specific, Kill-Switch Tumor Suppression Mechanism Dependent upon the Dramatic Adrenarchal Rise of Adrenal Androgens

Jonathan Wesley Nyce

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: p53; adrenarche; dehydroepiandrosterone; DHEA; DHEAS

Online: 12 April 2023 (07:38:17 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202304.0220.v1

Role of Phytochemicals and their Derivatives in Targeting Stem Cell Markers in Breast and Cervical Cancer

Kamran Waidha, Mehreen Aftab, Divyam Singh, Showket Hussain

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: breast cancer; cervical cancer; stem cells; docking; simulation; microRNA

Online: 11 April 2023 (10:14:48 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202304.0151.v1

The Surgical, Histopathological Characteristics, and Survival Outcome of Ovarian Clear Cell Carcinoma: A Retrospective Case Series Sharing the Experience of a Tertiary Cancer Centre over 10 Years

Sally EL Tawab, Sabina Nistor, Rene Roux, Sanjiv Manek, Kezia Geitskell, Ahmed Ahmed, Sean Kehoe, Hooman Soleymani majd

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Ovarian clear cell carcinoma; residual disease; recurrence; survival; endometriosis- associated

Online: 10 April 2023 (05:14:42 CEST)

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Preprint REVIEW | doi:10.20944/preprints202304.0038.v1

Serological Response to SARS-CoV-2 after COVID-19 Vaccination in Lung Cancer patients: Short Review

Ananda Rodilla, Sooyun Tavolacci, Jazz Cagan, Tanay Shah, Sandeep Mittan, Philip C. Mack, Fred R. Hirsch

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: lung cancer; SARS-CoV-2 vaccine; immunogenicity

Online: 4 April 2023 (04:58:31 CEST)

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Preprint COMMUNICATION | doi:10.20944/preprints202304.0032.v1

Development of Highly Sensitive Anti-Mouse CD39 Monoclonal Antibodies C₃₉Mab-1 and C₃₉Mab-2 for flow cytometry

Hiroyuki Suzuki, Yuma Kudo, Mayuki Tawara, Nohara Goto, Kenichiro Ishikawa, Tsunenori Ouchida, Tomohiro Tanaka, Teizo Asano, Takuro Nakamura, Miyuki Yanaka, Mika K. Kaneko, Yukinari Kato

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: mouse CD39; monoclonal antibody; the Cell-Based Immunization and Screening; CBIS

Online: 4 April 2023 (02:29:25 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202304.0027.v1

Engineering Adenoviral Vectors With Improved GBM Selectivity

Emily A Bates, Charlotte Lovatt, Alice R Plein, James A Davies, Florian A. Siebzehnrubl, Alan L Parker

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: brain tumour; oncolytic virus; receptor; therapy

Online: 3 April 2023 (13:31:42 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202303.0501.v1

Risk Factors of Breast Cancer Recurrence in Pathologic Complete Response Achieved by Patients Following Neoadjuvant Chemotherapy

Joon Young Choi, Doyoun Woen, Sung Yoon Jang, Hyunjun Lee, Dong Seung Shin, Youngji Kwak, Byung Joo Chae, Jonghan Yu, Jeong Eon Lee, Seok Won Kim, Seok Jin Nam, Jai Min Ryu

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Breast Neoplasm; Neoadjuvant Chemotherapy (NAC); pathologic Complete Response (pCR); Risk Factor; recurrence

Online: 29 March 2023 (03:52:14 CEST)

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Background: Pathologic complete response (pCR) of breast cancer after neoadjuvant chemotherapy (NAC) is highly related to molecular subtypes. Patients who achieved tumor pCR after NAC have a better prognosis. However, despite of better prognosis, pCR patients have a potential for recurrence. There is little evidence of risk factors of recurrence in patients with pCR. We aim to analyze factors associated with tumor recurrence in patients who achieved pCR. Methods: This study retrospectively reviewed the data of patients diagnosed with breast cancer who achieved pCR after receiving NAC between January 2009 and December 2018 in Samsung Medical Center. pCR was defined as no residual invasive cancer in the breast and axillary nodes even if there is residual ductal carcinoma in situ (ypT0 or ypTis with ypN0). Breast cancers are classified into 4 subtypes based on hormone receptors (HR) and human epithelial growth factor receptor 2 (HER2) status. Patients who had bilateral breast cancer, inflammatory breast cancer, distant metastasis, unknown subtype, and histologically unique case were excluded from the study. Results: In total 483 patients were included in this study except for patients who corresponded to the exclusion criteria. The median follow-up duration was 59.0 months (range, 0.5-153.3 months). Breast cancer recurred in 4.1% of patients (20 of 483). There was a significant difference in clinical T (p = .004) and clinical N (p = .034) stage in the Kaplan-Meier curve for disease-free survival. Molecular subtypes (p = .573), Ki67 (p = 1.000), and breast surgery type (p = .574) were not associated with tumor recurrence in patients who achieved pCR after NAC. In the clinical T stage and clinical N stage, there was a significant difference between recurrence and no-recurrence groups (clinical T stage; p = .045, clinical N stage; p = .002). Univariable Cox regression revealed statistical significance in the clinical T stage (p = .049) and clinical N stage (p = .010), while multivariable Cox regression demonstrated non-significance in the clinical T stage (p = .320) and clinical N stage (p = .073). Conclusion: Results in this study showed that clinical T, clinical N stage, and molecular subtypes were not statistically significant predictors of recurrence in patients who achieved pCR after NAC. It is hypothesized that a multicenter-based study would lead to the identification of factors as predictors of recurrence after achieving pCR.

Preprint ARTICLE | doi:10.20944/preprints202303.0491.v1

A Feasibility Study of Machine Learning Models for Cancer Rate Prediction

Shan Chen, Yuanzhao Ding

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Cancer; Incidence; Mortality; Artificial Intelligence; Machine learning; Neural network

Online: 28 March 2023 (14:10:14 CEST)

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Preprint REVIEW | doi:10.20944/preprints202303.0440.v1

Aiding Cancer’s “Sweet Tooth”: Role of Hexokinases in Metabolic Reprogramming

Zeenat Farooq, Hagar Ismail, Sheraz Bhat, Brian Layden, Md. Wasim Khan

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Cancer metabolism; HKDC1; Hexokinases; glucose metabolism; metabolic reprogramming

Online: 27 March 2023 (03:46:30 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202303.0431.v1

Somatic Evolution of Cancer: A New Synthesis

Ulfat Baing, Rohini Kharate, Milind Watve

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Cancer; wound healing; exaptation; somatic evolution

Online: 24 March 2023 (12:35:04 CET)

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Preprint REVIEW | doi:10.20944/preprints202302.0488.v2

Obesity Is Associated With Immunometabolic Changes in Adipose Tissue That May Drive Treatment Resistance in Breast Cancer: Immune-Metabolic Reprogramming and Novel Therapeutic Strategies

Constantinos Savva, Ellen Copson, Peter WM Johnson, Ramsey I Cutress, Stephen A Beers

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: breast cancer; obesity; inflammation; metabolism; treatment resistance

Online: 24 March 2023 (02:09:14 CET)

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Preprint ARTICLE | doi:10.20944/preprints202303.0407.v1

Willingness To Pay for HPV Vaccine Among Women Living With HIV in Nigeria

Folahanmi Akinsolu, Olunike Abodunrin, Ifeoluwa Adewole, Mobolaji Olagunju, Aisha O Gambari, Dolapo Raji, Ifeoma Idigbe, Diana W Njuguna, Abideen Salako, Oliver Ezechi

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: HPV, Cervical cancer, HPV vaccine, Women, HIV

Online: 23 March 2023 (02:45:10 CET)

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Preprint ARTICLE | doi:10.20944/preprints202303.0399.v1

A Novel Anti-CD44 Variant 9 Monoclonal Antibody C₄₄Mab-1 was Developed for Immunohistochemical Analyses Against Colorectal Cancers

Mayuki Tawara, Hiroyuki Suzuki, Tomohiro Tanaka, Mika K Kaneko, Yukinari Kato

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: CD44; CD44v9; monoclonal antibody; colorectal cancer

Online: 22 March 2023 (14:21:41 CET)

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Preprint ARTICLE | doi:10.20944/preprints202303.0360.v1

Double-Blind Parallel Treatment Randomized Controlled Trial of Prebiotics Efficacy for Severe Acute Malnutrition Children in Southern Punjab, Pakistan

Munazza Batool, Javeria Saleem, Rubeena Zakar, Sanaullah Iqbal, Ruhma Shahzad, Muhammad Salman Butt, Shahroz Haider, Florian Fischer

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: RUTF; prebiotics; SAM; CMAM; malnourishment

Online: 21 March 2023 (01:32:08 CET)

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Preprint REVIEW | doi:10.20944/preprints202303.0341.v1

COVID-19 Impact Analysis on Patients with Complex Health Conditions: A Literature Review

Xueping Peng, Guodong Long, Peng Yan, Wensi Tang, Allison Clarke

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: COVID-19 pandemic; impact analysis; data analytics; health care; vulnerable cohort; complex health condition

Online: 20 March 2023 (04:12:15 CET)

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Preprint REVIEW | doi:10.20944/preprints202208.0229.v6

Lipofuscin as the Main Driving Force of Current Age-Related Disease: Justification and Strategies for Removal

Michael Renteln

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Anti-aging therapy; lipofuscin; SENS; TFEB; telomerase; and intracellular microbes

Online: 20 March 2023 (03:43:19 CET)

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Preprint ARTICLE | doi:10.20944/preprints202303.0300.v1

Associations Between Health Behaviours, Gastrointestinal Symptoms, and Gut Microbiota in a Cross-Sectional Sample of Cancer Survivors: Secondary Analysis from the Chemo-Gut Study

Julie M. Deleemans, Faye Chleilat, Raylene A. Reimer, Mohamad Baydoun, Katherine-Ann Piedalue, Dana E. Lowry, Linda E. Carlson

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Health behaviors; gastrointestinal symptoms; gut microbiota; diet; exercise; cancer survivors

Online: 16 March 2023 (08:57:56 CET)

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Preprint COMMUNICATION | doi:10.20944/preprints202303.0269.v1

Preliminary Data: Feeding and Colon Cancer Growth. Modified Nitrogen Intake Leads to Blunted Cancer Growth Independently by Serine

Giovanni Corsetti, Claudia Romano, Tiziano Maria Scarabelli, Carol Chen-Scarabelli, Evasio Pasini, Francesco Saverio Dioguardi

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: cancer; amino acids; colon; nitrogen, diet, mice

Online: 15 March 2023 (03:12:31 CET)

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Preprint ARTICLE | doi:10.20944/preprints202303.0220.v1

18F-FDG PET-Derived Volume-Based Parameters To Predict Dis-Ease-Free Survival in Patients With Grade III Breast Cancer of Different Molecular Subtypes Candidates to Neoadjuvant Chem-Otherapy

Natale Quartuccio, Pierpaolo Alongi, Luca Urso, Naima Ortolan, Francesca Borgia, Mirco Bartolomei, Gaspare Arnone, Laura Evangelista

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: breast cancer; disease-free survival; semiquantitative paramaters; volume-based parameters; 18F-FDG; PET/CT

Online: 13 March 2023 (07:25:28 CET)

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Aim: This study aimed to investigate whether baseline 18F-FDG PET-derived semiquantitative parameters could predict disease-free survival in patients with grade III breast cancer of different molecular subtypes undergoing neoadjuvant chemotherapy (NAC). Materials and Methods: Patients were retrospectively retrieved from the databases of two Italian hospitals (University of Padua and University Hospital of Ferrara). Inclusion criteria were: 1) histologically proven diagnosis of grade III breast cancer; 2) history of NAC; 3) execution of a baseline 18F-FDG PET/CT scan before the start of NAC; 4) adequate follow-up time to compute the 3Y-DFS. For each 18F-FDG-PET/CT scan, the following parameters were calculated in the primary tumor (SUVmax, SUVmean, MTV, TLG) and whole-body (WB_SUVmax, WB_MTV, and WB_TLG). Receiver operating characteristic (ROC) analysis was used for each parameter to assess the prediction capability for 3Y-DFS. DFS differences between groups were assessed using Kaplan-Meier curves and compared by log-rank test. Results: Ninety-five grade III breast cancer patients with different molecular types were retrieved (luminal A: 5; luminal B: 34; luminal B-HER2: 22; HER2-enriched: 7; triple-negative: 27). In the whole group of patients, WB_SUVmax was the best predictor of recurrence (AUC: 0.66; best cut-off: WB_SUVmax>9.43; SS: 96%; SP: 38.1%; p<0.008). Patients with luminal A and Her-2-enriched breast cancer types were excluded from the molecular subgroup analysis due to the small study samples (5 and 7, respectively). In luminal B patients (n=34), WB_MTV (AUC: 0.75; best cut-off: WB_MTV>195.33; SS: 55.56%, SP: 100%; p=0.002) and WB_TLG (AUC: 0.73; best cut-off: WB_TLG>1066.21; SS: 55.56%, SP: 100%; p=0.05) were the best predictors of 3Y-DFS. Patients had a higher probability of DFS in case of a WB_MTV≤195.33 (3429±210 vs. 446±144 days; p<0.001) or WB_TLG≤ 1066.33 (937.35±19 vs. 496±131 days; p<0.001). In luminal B-HER2 patients (n=22), WB_SUVmax was the only predictor of 3Y-DFS (AUC: 0.857; best cut-off: WB_SUVmax>13.12; SS: 100%; SP: 71.43%; p<0.001); patients with WB_SUVmax≤13.12 had a significantly longer DFS (3857 days) than patients with a WB_SUVmax >13.12 (1693±430 days; p<0.004). No parameter resulted significant in the prediction of 3Y-DFS in patients with grade III triple-negative cancer. Conclusion: Volume-based parameters, extracted from baseline 18F-FDG PET, seem to be promising tools in the prediction of recurrence within 3 years in patients with grade III luminal B and luminal B- HER2 breast cancer undergoing NAC. Larger study samples are needed to confirm these preliminary findings.

Preprint ARTICLE | doi:10.20944/preprints202303.0147.v1

An In-Vitro Approach to Model EMT in Breast Cancer

Lorenz Isert, Aditi Mehta, Gabriele Loiudice, Altea Oliva, Andreas Roidl, Olivia Merkel

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: breast cancer; EMT; tumor microenvironment; collagen coatings; EMT-phenotyping; shape factors

Online: 8 March 2023 (06:29:48 CET)

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Preprint ARTICLE | doi:10.20944/preprints202303.0082.v1

CENPA Was a Cell Cycle Biomarker in Cancers With Diagnostic Prognostic, and Therapeutic Value

Hengrui Liu, Tao Tang

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: CENPA; cell cycle; pan-cancer; diagnostic; prognostic; glioma; immune; protein-ligand docking

Online: 6 March 2023 (02:38:13 CET)

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Preprint ARTICLE | doi:10.20944/preprints202301.0421.v3

Drawbacks of Immune Checkpoint Inhibition and Rigorous Management for Immune Related Adverse Events Along with a Mathematical Model to Assess Therapy Success and Optimum Therapy Duration and a Strategy Against Tumor Plasticity

C. Mehmet Hendekli

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Oncology; Immune Checkpoint Inhibition; PD-1; PD-L1; CTLA-4; Immune Related Adverse Events; Immunotherapy; Tumor Plasticity; Tumor Microenvironment; Optimum Therapy Duration

Online: 6 March 2023 (01:53:16 CET)

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Preprint BRIEF REPORT | doi:10.20944/preprints202212.0579.v3

Known Modifiable Risk Factors of Cancer

Angel Justiz-Vaillant, Darren Gopaul

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Lifestyle; diet; carcinogenesis; tobacco; alcohol; cancer-related microorganisms

Online: 3 March 2023 (10:19:18 CET)

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Preprint ARTICLE | doi:10.20944/preprints202303.0060.v1

Assessing the Relationship Between Gastrointestinal and Pancreatic Neuroendocrine Tumor Grade and Overall Survival: A Systematic Review and Meta-Analysis

Aysha Aslam, Preeti Malik, Azadeh Khayat, Muhammed Asad, Rizwan Rabbani, Sameer Dawodi, Neel Patel, Sangeetha Chandramohan, Nkechi Unachukwu, Bibimariyam Nasyrlaeva, Laseena Vaisyambath, Sriram Chowdary, Vikramaditya Samala Venkata, Urvish Patel

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Neuroendocrine tumors; survival; meta-analysis; NET; gastropancreatic NET; systemic review

Online: 3 March 2023 (06:59:20 CET)

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Preprint ARTICLE | doi:10.20944/preprints202303.0015.v1

Developing a Supplementary Diagnostic Tool for Breast Cancer Risk Estimation Using Ensemble Transfer Learning

Tengku Muhammad Hanis, Nur Intan Raihana Ruhaiyem, Wan Nor Arifin, Juhara Haron, Wan Faiziah Wan Abdul Rahman, Rosni Abdullah, Kamarul Imran Musa

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Asian women; breast cancer; transfer learning; artificial intelligence

Online: 1 March 2023 (08:51:04 CET)

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Preprint REVIEW | doi:10.20944/preprints202302.0488.v1

Obesity Is Associated With Immunometabolic Changes in Adi-Pose Tissue That May Drive Treatment Resistance in Breast Cancer: Immune-Metabolic Reprogramming and Novel Therapeutic Strategies

Constantinos Savva, Ellen Copson, Peter WM Johnson, Ramsey I Cutress, Stephen A Beers

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: breast cancer; obesity; inflammation; metabolism; treatment resistance

Online: 28 February 2023 (02:26:46 CET)

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White adipose tissue (WAT) has evolved to slowly mobilise energy stores in the form of lipids and a dynamic endocrine and immunologically active organ that regulates energy homeostasis. Breast WAT is involved not only in the biosynthesis of important molecular mediators but is also reported to be linked to the metastatic potential of breast tumours. The role of adiposity and consequently the role of systemic inflammation in immune responses and resistance to anti-cancer treatment in breast cancer (BC) patients is however still not clear. This review aims to evaluate the emerging evidence on the crosstalk between adiposity and the immune-tumour microenvironment in BC, its progression and treatment resistance. Adiposity, and by extension subclinical inflammation, are associated with metabolic dysfunction and changes in the immune-tumour microenvironment in BC. In oestrogen receptor positive (ER+) breast tumours, it is proposed that these changes are mediated via a paracrine interaction between macrophages and preadipocytes leading to elevated aromatase expression and secretion of pro-inflammatory cytokines and adipokines in the breast tissue in patients who are obese or overweight. In HER2+ breast tumours, WAT inflammation has been reported to induce trastuzumab resistance via activation of MAPK or PI3K signalling pathways. Furthermore, adipose tissue in patients with obesity is associated with upregulation of immune checkpoints on T-cells that is partially mediated via immunomodulatory effects of leptin and has been paradoxically associated with improved responses to immunotherapy in several cancers. In conclusion, evidence suggests that body composition and metabolic status are associated with patient outcomes. In order to optimise patient stratification and personalisation of treatment prospective studies are required to evaluate the role of body composition and metabolic parameters in metabolic immune reprogramming with and without immunotherapy in patients with BC.

Preprint REVIEW | doi:10.20944/preprints202212.0579.v2

Known Modifiable Risk Factors of Cancers

Angel Justiz-Vaillant, Darren Gopaul

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: carcinogenesis; lifestyle; diet

Online: 27 February 2023 (08:39:41 CET)

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Preprint ARTICLE | doi:10.20944/preprints202302.0419.v1

Self-Employed Canadians’ Experiences with Cancer and Work: A Qualitative Study

Christine Maheu, Maureen Parkinson, Caitlin Wong, Fatima Yashmin, Caroline Longpré

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: self-employed; cancer; work; return to work; cancer survivors

Online: 24 February 2023 (04:44:52 CET)

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Preprint ARTICLE | doi:10.20944/preprints202302.0363.v1

Characterization of Spatial Heterogeneity in Metastasized Colorectal Cancer by MALDI Imaging

Lennart Moritz, Maren Nicole Stillger, Ferenc Takács, Hannah Füllgraf, Martin Werner, Stefan Fichtner-Feigl, Andreas Jud, Oliver Schilling, Melanie Christine Föll

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: colorectal cancer; metastasis; tumor heterogeneity; spatial proteomics; mass spectrometry imaging; MALDI imaging; formalin-fixed paraffin-embedded tissues

Online: 21 February 2023 (11:21:41 CET)

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Preprint ARTICLE | doi:10.20944/preprints202301.0421.v2

Drawbacks of Immune Checkpoint Inhibition and Rigorous Management for Immune Related Adverse Events Along with a Strategy Against Tumor Plasticity

C. Mehmet Hendekli

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Oncology; Immune Checkpoint Inhibition; PD-1; PD-L1; CTLA-4; Immune Related Adverse Events; Immunotherapy; Tumor Plasticity; Tumor Microenvironment

Online: 16 February 2023 (07:54:31 CET)

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Preprint ARTICLE | doi:10.20944/preprints202302.0274.v1

Dynamic Vascular Imaging Using Active Breast Thermography

Meir Gershenson, Jonathan Peter Gershenson

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Breast cancer; components analysis; dynamic thermogram; vasomodulation; veins; virtual wave; equivalent wave field

Online: 16 February 2023 (06:32:33 CET)

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Preprint ARTICLE | doi:10.20944/preprints202210.0296.v2

Wild-type N-Ras Complements Mutant K-Ras in Pancreatic Cancer Cell Lines but K-Ras has a Specific Role in Cell Cycle Independent Regulation of G2 Cyclins

Robert Ferguson, Karen Aughton, Anthony Evans, Victoria Shaw, Jane Armstron, Adam Ware, Laura Bennett, Eithne Costello, William Greenhalf

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Pancreatic Ductal Adenocarcinoma; K-Ras; N-Ras; G2 cyclins

Online: 16 February 2023 (03:22:47 CET)

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Preprint REVIEW | doi:10.20944/preprints202302.0240.v1

Employing Mesenchymal Stromal Cells (MSC) for Managing Acute and Chronic Graft-versus-Host-Disease

Mohini Mendiratta, Meenakshi Mendiratta, Sujata Mohanty, Ranjit Kumar Sahoo, Hridayesh Prakash

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Mesenchymal Stromal Cells; Graft-versus-Host-Disease; Immunomodulation; Apoptosis; Efferocytosis; Secretome

Online: 14 February 2023 (08:39:01 CET)

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Preprint REVIEW | doi:10.20944/preprints202302.0205.v1

BRCA Mutations: The Achilles Heel of Breast, Ovarian and Other Epithelial Cancers

Anna P. Loboda, Leonid S. Adonin, Svetlana D. Zvereva, Nikolay B. Pestov, Dmitri Y. Guschin, Tatyana V. Korneenko, Alexandra V. Telegina, Olga K. Kondratieva, Sofia E. Frolova, Nickolai A. Barlev

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: breast cancer; ovarian cancer; PARP inhibitors; Alu repeats; protein-protein interactions

Online: 13 February 2023 (07:54:35 CET)

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Preprint ARTICLE | doi:10.20944/preprints202302.0183.v1

Evaluation of Mitochondrial Function in Blood Samples Shows Distinct Patterns in Subjects with Thyroid Carcinoma from Those with Hyperplasia

Julia Bernal-Tirapo, María Teresa Bayo-Jimenez, Pedro Yuste-García, Isabel Córdova-Oriz, Ana Peñas, Francisco-Javier García-Borda, Cesar Quintela, Ignacio Prieto, Cristina Sánchez-Ramos, Eduardo Ferrero-Herrero, María Monsalve

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: metabolism; mitochondria; cancer; thyroid; diagnostic

Online: 10 February 2023 (07:28:05 CET)

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Metabolic adaptations are a hallmark of cancer and may be exploited to develop novel diagnostic and therapeutic tools. Only about 50% of the patients who undergo thyroidectomy due to suspicion of thyroid cancer actually have the disease, highlighting the diagnostic limitations of current tools. We explored the possibility of using non-invasive blood tests to accurately diagnose thyroid cancer. We analyzed blood and thyroid tissue samples from 2 independent cohorts of patients undergoing thyroidectomy at the Hospital Universitario 12 de Octubre (Madrid, Spain). As expected, histological comparisons of thyroid cancer and hyperplasia revealed higher proliferation and apoptotic rates and enhanced vascular alterations in the former. Notably, they also revealed increased levels of membrane-bound phosphorylated AKT, suggestive of enhanced glycolysis, and alterations in mitochondrial sub-cellular distribution. Both characteristics are common metabolic adaptations in primary tumors. These data together with reduced mtDNA copy number and elevated levels of the mitochondrial antioxidant Prx3 in cancer tissue samples suggest the presence of mitochondrial oxidative stress. In plasma, cancer patients showed higher levels of cfDNA and mtDNA. Of note, mtDNA plasma levels inversely correlated with those in the tissue, suggesting that higher death rates were linked to lower mtDNA copy number. In PBMCs, cancer patients showed higher levels of PGC-1, a positive regulator of mitochondrial function, but this increase was not associated with a corresponding induction of its target genes, suggesting a reduced activity in cancer patients. We also observed a significant difference in the PRDX3/PFKFB3 correlation at the gene expression level, between carcinoma and hyperplasia patients, also indicative of increased systemic metabolic stress in cancer patients. The correlation of mtDNA levels in tissue and PBMCs further stressed the interconnection between systemic and tumor metabolism. Evaluation of the mitochondrial gene ND1 in plasma, PBMCs and tissue samples, suggested that it could be a good biomarker for systemic oxidative metabolism, with ND1/mtDNA ratio positively correlating in PBMCs and tissue samples. In contrast, ND4 evaluation would be informative of tumor development, with ND4/mtDNA ratio specifically altered in the tumor context. Taken together, our data suggest that metabolic dysregulation in thyroid cancer can be monitored accurately in blood samples and might be exploited for the accurate discrimination of cancer from hyperplasia.

Preprint REVIEW | doi:10.20944/preprints202302.0122.v1

Relationship between Osteosarcoma Therapy and Tumorigenesis, Metastasis, Immune Evasion, and Chemoresistance

Yan Yik Lim, Ahmad Mujahid Ahmad Zaidi, Mainul Haque, Azizi Miskon

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Osteosarcoma; Tumorigenesis; Metastasis; Immune Evasion; Chemoresistance; Mutation

Online: 7 February 2023 (06:12:43 CET)

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Preprint ARTICLE | doi:10.20944/preprints202302.0100.v1

Development of Surface-Modified Mesenchymal Stem Cells with Liposomes via Electrostatic Interactions for Tumor Targeted Drug Delivery

Yusuke Kono, Renpei Kamino, Soma Hirabayash, Takuya Kishimoto, Mika Hosokawa, Ken-ichi Ogawara

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: mesenchymal stem cell; drug delivery; surface modification; electrostatic interaction; magnetic liposome

Online: 6 February 2023 (10:07:55 CET)

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Preprint REVIEW | doi:10.20944/preprints202302.0030.v1

Analysis of Efficacy/Safety Ratio of Angiogenesis-inhibitors based Therapies in Ovarian Cancer: A Comprehensive Meta-analysis

Laurentiu Simion, Vlad Rotaru, Ciprian Cirimbei, Daniela-Cristina Ştefan, Mirela Gherghe, Sinziana Ionescu, Bogdan Cosmin Tănase, Dan Cristian Luca, Laurentia Nicoleta Gales, Elena Chitoran

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: angiogenesis inhibitors; VEGF inhibitors; ovarian cancer; progression-free survival; overall sur-vival; toxicity; systematic review; meta-analysis; randomized controlled trials; FDA approval of cancer drugs

Online: 2 February 2023 (05:26:47 CET)

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Preprint ARTICLE | doi:10.20944/preprints202302.0025.v1

CT Radiomics and Clinical Feature Model to Predict Lymph Node Metastases in Early-Stage Testicular Cancer

Catharina Silvia Lisson, Sabitha Manoj, Daniel Wolf, Jasper Schrader, Stefan Andreas Schmidt, Meinrad Beer, Michael Goetz, Friedemann Zengerling, Christoph Gehard Lisson

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: radiomics signature; prediction; machine learning; testicular cancer; personalised oncology; precision imaging

Online: 2 February 2023 (03:15:05 CET)

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Accurate retroperitoneal lymph node metastasis (LNM) prediction in early-stage testicular germ cell tumours (TGCT) harbours the potential to significantly reduce over- or undertreatment and treatment-related morbidity in this group of young patients as an important survivorship imperative. We investigated the role of computed tomography (CT) radiomics models integrating clinical predictors for the individualized prediction of LNM in early-stage TGCT. Ninety-one patients with surgically proven testicular germ cell tumours and contrast-enhanced CT were included in this retrospective study. Dedicated radiomics software was used to segment 273 retroperitoneal lymph nodes and extract features. After feature selection, radiomics-based machine learning models were developed to predict LN metastasis. The robustness of the procedure was controlled by 10-fold cross-validation. Using multivariable logistic regression modelling, we developed three prediction models: A radiomics-only model, a clinical-only model and a combined radiomics-clinical model. The models' performance was evaluated using the area under the receiver operating characteristic curve (AUC). Finally, decision curve analysis was performed to estimate the clinical usefulness of the predictive model. The radiomics-only model for predicting lymph node metastasis reached a greater discrimination power than the clinical-only model, with an AUC of 0.84 (± 0.17; 95% CI ) vs 0.60 (± 0.22; 95% CI) in our study cohort. The combined model integrating clinical risk factors and selected radiomics features outperformed the clinical-only and the radiomics-only prediction models and showed good discrimination with an area under the curve of 0.94 ( ± 0.10; 95% CI). The decision curve analysis demonstrated the clinical usefulness of our proposed combined model. The presented combined CT-based radiomics-clinical model represents an exciting non-invasive prediction tool for individualized prediction of LN metastasis in testicular germ cell tumours. Multi-centre validation is required to generate high-quality evidence for its clinical application.

Preprint ARTICLE | doi:10.20944/preprints202212.0444.v2

First Live-Experience Session with PET/CT Specimen Imager. A pilot analysis in Prostate Cancer and Neuroendocrine Tumor

Lorenzo Muraglia, Francesco Mattana, Laura Lavinia Travaini, Gennaro Musi, Emilio Bertani, Giuseppe Renne, Eleonora Pisa, Mahila Esmeralda Ferrari, Uberto Fumagalli Romario, Ottavio De Cobelli, Nicola Fusco, Francesco Ceci

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: PET/CT; PET; PET/CT specimen imager; radio-guided surgery

Online: 2 February 2023 (02:30:52 CET)

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Objective: to evaluate the feasibility of the intra-operative application of a specimen PET/CT imager in a clinical setting. Materials and methods: this is a pilot analysis performed in three patients who received an intra-operative administration of 68Ga-PSMA-11 (n=2) and 68Ga-DOTA-TOC (n=1), respectively. Patients were administrated with PET radiopharmaceuticals to perform radio-guided surgery with a beta-probe detector during radical prostatectomy for prostate cancer (PCa) and salvage lymphadenectomy for recurrent neuroendocrine tumor (NET) of the ileum, respectively. All procedures have been performed within two ongoing clinical trials in our Institute (NCT05596851 and NCT05448157). Pathologic assessment with immunohistochemistry (PSMA-staining and SSA immunoreactivity) was considered as standard of truth. Specimen images were compared with baseline PET/CT images and histopathological analysis. Results: Patients received 1 MBq/Kg of 68Ga-PSMA-11 (PCa) or 1.2 MBq/Kg of 68Ga-DOTA-TOC (NET) prior to surgery. Specimens were collected, positioned in the dedicated specimen container, and scanned to obtain high resolution PET/CT images. In all cases a perfect match was observed between the findings detected by the specimen imager and histopathology. Overall, the PET spatial resolution was sensibly higher for the specimen images compared to the baseline whole-body PET/CT images. Furthermore, the use of the PET/CT specimen imager did not significantly interfere with any procedures, and the overall length of the surgery was not affected using the PET/CT specimen imager. Finally, the radiation exposure of the operating theater staff was lower than 40 µSv per procedure (range 26 – 40 Sv). Conclusion: the image acquisition of specimens obtained by patients who received intra-surgery injection of 68Ga-PSMA-11 and 68Ga-DOTA-TOC was feasible and reliable also in a live-experience session and has been easily adapted to surgery daily-practice. The high sensitivity, together with the evaluation of intra-lesion tumor heterogeneity, were the most relevant results since the data derived from specimen PET/CT imaging matched perfectly with the histopathological analysis.

Preprint CASE REPORT | doi:10.20944/preprints202302.0016.v1

First Evidence of Activity of Enfortumab Vedotin on Brain Metastases in Urothelial Cancer Patients

Christof Vulsteke, Laurens De Cocker, Alfonso Gómez de Liaño, Cristina Montesdeoca, Astrid De Meulenaere, Lieselot Croes, Danielle Delombaerde, Bernadett Szabados, Thomas Powles

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: enfortumab vedotin; brain metastases; antibody-drug conjugate

Online: 1 February 2023 (16:46:24 CET)

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Abstract: Enfortumab vedotin (EV), an antibody-drug conjugate directed against Nectin-4, signif-icantly prolonged survival when compared with standard chemotherapy in patients with locally advanced or metastatic urothelial carcinoma who previously received platinum-based chemo-therapy and a PD-1 or PD-L1 inhibitor. The confirmed overall response rate in the phase 3 EV301 trial leading to approval was 40.6%. However, no data have been published about the activity in brain metastases. Here, we present three patients from different centers with brain metastases receiving EV. A 58-year-old male Caucasian patient, who was heavily pretreated for urothelial carcinoma with visceral metastases and a solitary clinically active brain metastasis, started on EV 1.25 mg/kg on days 1, 8, and 15 of a 28-day cycle. The first evaluation after three cycles of EV showed a partial remission by RECIST v1.1 with a near complete response in the brain metastasis and disappear-ance of the neurological complaints. The patient is currently still receiving EV. A second, 74-year-old male patient started on the same regimen, after previous progression on platinum-based chemotherapy and maintenance avelumab. The patient achieved complete response and remained on therapy for five months. However, therapy was discontinued at the patient’s re-quest. Shortly after, he developed new leptomeningeal metastases. Upon rechallenge with EV, there was a significant reduction in the diffuse meningeal infiltration. A third, 50-year-old male Caucasian patient also received EV, after previous progression on cisplatin-gemcitabine and ate-zolizumab maintenance followed by palliative whole brain radiotherapy and two cycles of vin-flunine. The first evaluation after three cycles of EV showed a significant reduction of the brain metastases. The patient is currently still receiving EV. These are the first reports on efficacy of EV in patients with urothelial carcinoma and active brain metastases.

Preprint ARTICLE | doi:10.20944/preprints202301.0581.v1

Development of a Novel Anti-CD44 Variant 5 Monoclonal Antibody C₄₄Mab-3 for Multiple Applications against Pancreatic Carcinomas

Yuma Kudo, Hiroyuki Suzuki, Tomohiro Tanaka, Mika K. Kaneko, Yukinari Kato

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: CD44; CD44 variant 5; monoclonal antibody; flow cytometry; immunohistochemistry

Online: 31 January 2023 (09:08:35 CET)

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Preprint REVIEW | doi:10.20944/preprints202301.0567.v1

Mechanistic Insights on Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer

Olivia G Huffman, Danielle B Chau, Andreea I Dinicu, Robert DeBernardo, Ofer Reizes

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: hyperthermia; ovarian cancer; immunity; chemotherapy; HIPEC

Online: 31 January 2023 (02:41:11 CET)

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Preprint REVIEW | doi:10.20944/preprints202301.0519.v1

Genetic Risk Scores and Missing Heritability in Ovarian Cancer

James P Brody, Yasaman Fatapour

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: ovarian cancer; machine learning; germ line; genetic risk scores

Online: 28 January 2023 (06:58:55 CET)

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Preprint ARTICLE | doi:10.20944/preprints202301.0454.v1

Stress-inducible SCAN Factors Suppress the Stress Response and Are Biomarkers for Enhanced Prognosis in Cancers

Takanori Eguchi, Mona Sheta, Stuart K Calderwood

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: cell stress response; heat shock protein 90 (HSP90); SCAN domain-containing proteins (SCAND); MZF1; heat shock factors (HSF); co-expression correlation; Kaplan-Meyer analysis; cancer patients prognosis

Online: 25 January 2023 (10:18:20 CET)

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Preprint ARTICLE | doi:10.20944/preprints202301.0434.v1

Pan-cancer evaluation of clinical value of mitotic network activity index (MNAI) and its predictive value of immunotherapy

Xuanyu Mao, Yimeng Cai, Sarah Long, Jesus Perez-Losada, Jian-Hua Mao, Hang Chang

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: pan-cancer; mitotic network activity index; prognostic biomarker; genetic instability; immunotherapy; multimodal biomarker; cellular morphometric subtype

Online: 24 January 2023 (13:23:26 CET)

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Preprint ARTICLE | doi:10.20944/preprints202301.0421.v1

Drawbacks of Immune Checkpoint Inhibition and Rigorous Management for Immune Related Adverse Events Along with a Strategy Against Tumor Plasticity

C. Mehmet Hendekli

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Oncology, Immune Checkpoint Inhibition, PD-1, PD-L1, CTLA-4, Immune Related Adverse Events, Immunotherapy, Tumor Plasticity, Tumor Microenvironment

Online: 24 January 2023 (03:27:37 CET)

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Preprint ARTICLE | doi:10.20944/preprints202301.0376.v1

Artificial Diets with Altered Levels of Sulfur Amino Acids Induce Anticancer Activity in Mice with Metastatic Colon Cancer, Ovarian Cancer and Renal Cell Carcinoma

Julio José Jiménez-Alonso, Emilio Guillén-Mancina, José Manuel Calderón-Montaño, Víctor Jiménez-González, Patricia Díaz-Ortega, Estefanía Burgos-Morón, Miguel López-Lázaro

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: sulphur amino acids; anticancer activity; metastasis; cancer metabolism; colorectal cancer; ovari-an cancer; renal cancer; methionine; cysteine; taurine; amino acids

Online: 22 January 2023 (04:09:19 CET)

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Preprint ARTICLE | doi:10.20944/preprints202301.0325.v1

Foxp3 and CD68 as Potential Predictors of Response to Immune Checkpoint Inhibitors in Patients with Advanced Solid Tumor

Peter Grell, Simona Borilova, Pavel Fabian, Iveta Selingerova, David Novak, Petr Muller, Igor Kiss, Rostislav Vyzula

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Immune checkpoint inhibitors; Anti-tumor immunity; Predictive biomarker; Malignant melanoma; NSCLC

Online: 18 January 2023 (08:39:18 CET)

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Medicine and Pharmacology