Proteomic analysis of dorsal root ganglia in a mouse model of paclitaxel-induced neuropathic pain.

Paclitaxel is a chemotherapy drug widely used for the treatment of various cancers based on its ability to potently stabilize cellular microtubules and block division in cancer cells. Paclitaxel-based treatment, however, accumulates in peripheral system sensory neurons and leads to a high incidence rate (over 50%) of chemotherapy induced peripheral neuropathy in patients. Using an established preclinical model of paclitaxel-induced peripheral neuropathy (PIPN), we examined proteomic changes in dorsal root ganglia (DRG) of adult male mice that were treated with paclitaxel (8 mg/kg, at 4 injections every other day) relative to vehicle-treated mice.

The Innate Immune System and the TRAIL-Bcl-XL Axis Mediate a Sex Bias in Lung Cancer and Confer a Therapeutic Vulnerability in Females.

There is a significant sex bias in lung cancer, with males showing increased mortality compared with females. A better mechanistic understanding of these differences could help identify therapeutic targets to personalize cancer therapies to each sex. After observing a clear sex bias in humanized mice, with male patient-derived xenograft lung tumors being more progressive and deadlier than female patient-derived xenograft lung tumors, we identified mouse tumor models of lung cancer with the same sex bias.

The Prediction of Biological Features Using Magnetic Resonance Imaging in Head and Neck Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis.

Magnetic resonance imaging (MRI) is an indispensable, routine technique that provides morphological and functional imaging sequences. MRI can potentially capture tumor biology and allow for longitudinal evaluation of head and neck squamous cell carcinoma (HNSCC). This systematic review and meta-analysis evaluates the ability of MRI to predict tumor biology in primary HNSCC.

Lymph node-targeting adjuvant/neoantigen-codelivering vaccines for combination glioblastoma radioimmunotherapy.

Glioblastoma multiforme (GBM) is the most common and lethal type of adult brain cancer. Current GBM standard of care, including radiotherapy, often ends up with cancer recurrence, resulting in limited long-term survival benefits for GBM patients. Immunotherapy, such as immune checkpoint blockade (ICB), has thus far shown limited clinical benefit for GBM patients.

External validation of an MR-based radiomic model predictive of locoregional control in oropharyngeal cancer.

Objectives: To externally validate a pre-treatment MR-based radiomics model predictive of locoregional control in oropharyngeal squamous cell carcinoma (OPSCC) and to assess the impact of differences between datasets on the predictive performance.

Methods: Radiomic features, as defined in our previously published radiomics model, were extracted from the primary tumor volumes of 157 OPSCC patients in a different institute. The developed radiomics model was validated using this cohort.

Strategies for tackling the class imbalance problem of oropharyngeal primary tumor segmentation on magnetic resonance imaging.

Background And Purpose: Contouring oropharyngeal primary tumors in radiotherapy is currently done manually which is time-consuming. Autocontouring techniques based on deep learning methods are a desirable alternative, but these methods can render suboptimal results when the structure to segment is considerably smaller than the rest of the image. The purpose of this work was to investigate different strategies to tackle the class imbalance problem in this tumor site.

Largest diameter delineations can substitute 3D tumor volume delineations for radiomics prediction of human papillomavirus status on MRI's of oropharyngeal cancer.

Purpose: Laborious and time-consuming tumor segmentations are one of the factors that impede adoption of radiomics in the clinical routine. This study investigates model performance using alternative tumor delineation strategies in models predictive of human papillomavirus (HPV) in oropharyngeal squamous cell carcinoma (OPSCC).

Methods: Of 153 OPSCC patients, HPV status was determined using p16/p53 immunohistochemistry.

In Vivo Imaging to Measure Spontaneous Lung Metastasis of Orthotopically-injected Breast Tumor Cells.

Metastasis remains the primary cause of cancer-related death. The succession of events that characterize the metastatic cascade presents multiple opportunities for therapeutic intervention, and the ability to accurately model them in mice is critical to evaluate their effects. Here, a step-by-step protocol is presented for the establishment of orthotopic primary breast tumors and the subsequent monitoring of the establishment and growth of metastatic lesions in the lung using in vivo bioluminescence imaging.

Identifying high-risk colon cancer on CT an a radiomics signature improve radiologist's performance for T staging?

Purpose: To assess the role of radiomics in detection of high-risk (pT3-4) colon cancer and develop a combined model that combines both radiomics and CT staging of colon cancer.

Methods: We included 292 colon cancer patients who underwent pre-operative CT and primary surgical resection within 2 months. Three-dimensional segmentations and CT staging of primary colon tumors were done.

Simple delineations cannot substitute full 3d tumor delineations for MR-based radiomics prediction of locoregional control in oropharyngeal cancer.

Background And Purpose: Manual delineation of head and neck tumor contours for radiomics analyses is tedious and time consuming. This study investigates if fast or readily available tumor contours can substitute full tumor contours by an experienced observer for an MR-based radiomics model to predict locoregional control (LRC) in oropharyngeal squamous cell carcinoma (OPSCC) tumors.

Materials And Methods: Radiomic features were extracted from postcontrast T1-weighted MRIs of 177 OPSCC primary tumors using six different manual delineation strategies.

Prognostic functional MR imaging parameters in head and neck squamous cell carcinoma: A systematic review.

Objective: Functional MR imaging has demonstrated potential for predicting treatment response. This systematic review gives an extensive overview of the current level of evidence for pre-treatment MR-based perfusion and diffusion imaging parameters that are prognostic for treatment outcome in head and neck squamous cell carcinoma (HNSCC) (PROSPERO registrationCRD42020210689).

Materials And Methods: According to the PRISMA statements, Medline, Embase and Scopus were queried for articles with a maximum date of October 19th, 2020.

Oropharyngeal primary tumor segmentation for radiotherapy planning on magnetic resonance imaging using deep learning.

Background And Purpose: Segmentation of oropharyngeal squamous cell carcinoma (OPSCC) is needed for radiotherapy planning. We aimed to segment the primary tumor for OPSCC on MRI using convolutional neural networks (CNNs). We investigated the effect of multiple MRI sequences as input and we proposed a semi-automatic approach for tumor segmentation that is expected to save time in the clinic.

Improved outcome prediction of oropharyngeal cancer by combining clinical and MRI features in machine learning models.

Objectives: New markers are required to predict chemoradiation response in oropharyngeal squamous cell carcinoma (OPSCC) patients. This study evaluated the ability of magnetic resonance (MR) radiomics to predict locoregional control (LRC) and overall survival (OS) after chemoradiation and aimed to determine whether this has added value to traditional clinical outcome predictors.

Methods: 177 OPSCC patients were eligible for this study.

Autophagy-Dependent Sensitization of Triple-Negative Breast Cancer Models to Topoisomerase II Poisons by Inhibition of the Nucleosome Remodeling Factor.

Epigenetic regulators can modulate the effects of cancer therapeutics. To further these observations, we discovered that the bromodomain PHD finger transcription factor subunit (BPTF) of the nucleosome remodeling factor (NURF) promotes resistance to doxorubicin, etoposide, and paclitaxel in the 4T1 breast tumor cell line. BPTF functions in promoting resistance to doxorubicin and etoposide, but not paclitaxel, and may be selective to cancer cells, as a similar effect was not observed in embryonic stem cells.

Unexpected PD-L1 immune evasion mechanism in TNBC, ovarian, and other solid tumors by DR5 agonist antibodies.

Lack of effective immune infiltration represents a significant barrier to immunotherapy in solid tumors. Thus, solid tumor-enriched death receptor-5 (DR5) activating antibodies, which generates tumor debulking by extrinsic apoptotic cytotoxicity, remains a crucial alternate therapeutic strategy. Over past few decades, many DR5 antibodies moved to clinical trials after successfully controlling tumors in immunodeficient tumor xenografts.

Regulatory T Cells Support Breast Cancer Progression by Opposing IFN-γ-Dependent Functional Reprogramming of Myeloid Cells.

Regulatory T (Treg) cell infiltration of solid tumors often correlates with poor prognosis, but their tumor-suppressive function lacks mechanistic understanding. Through a combination of transgenic mice, cell fate mapping, adoptive transfer, and co-injection strategies, we demonstrate that Treg cell ablation-dependent anti-tumor effects in murine breast cancer require intratumoral recruitment of CCR2 inflammatory monocytes, which primarily differentiate into tumor-associated macrophages (TAMs), and lead to reprogramming of their function in an IFN-γ-dependent manner. Furthermore, transcriptomic signatures from murine TAMs in Treg cell-ablated conditions correlate with increased overall survival in human breast cancer.

Local Targeting of Lung-Tumor-Associated Macrophages with Pulmonary Delivery of a CSF-1R Inhibitor for the Treatment of Breast Cancer Lung Metastases.

The lungs are major sites of metastases for several cancer types, including breast cancer (BC). Prognosis and quality of life of BC patients that develop pulmonary metastases are negatively impacted. The development of strategies to slow the growth and relieve the symptoms of BC lung metastases (BCLM) is thus an important goal in the management of BC.

Clinical variables and magnetic resonance imaging-based radiomics predict human papillomavirus status of oropharyngeal cancer.

Background: Human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) have better prognosis and treatment response compared to HPV-negative OPSCC. This study aims to noninvasively predict HPV status of OPSCC using clinical and/or radiological variables.

Methods: Seventy-seven magnetic resonance radiomic features were extracted from T1-weighted postcontrast images of the primary tumor of 153 patients.

Brain Metastasis Cell Lines Panel: A Public Resource of Organotropic Cell Lines.

Spread of cancer to the brain remains an unmet clinical need in spite of the increasing number of cases among patients with lung, breast cancer, and melanoma most notably. Although research on brain metastasis was considered a minor aspect in the past due to its untreatable nature and invariable lethality, nowadays, limited but encouraging examples have questioned this statement, making it more attractive for basic and clinical researchers. Evidences of its own biological identity (i.

Gross tumour volume delineation in anal cancer on T2-weighted and diffusion-weighted MRI - Reproducibility between radiologists and radiation oncologists and impact of reader experience level and DWI image quality.

Purpose: To assess how gross tumour volume (GTV) delineation in anal cancer is affected by interobserver variations between radiologists and radiation oncologists, expertise level, and use of T2-weighted MRI (T2W-MRI) vs. diffusion-weighted imaging (DWI), and to explore effects of DWI quality.

Methods And Materials: We retrospectively analyzed the MRIs (T2W-MRI and b800-DWI) of 25 anal cancer patients.

Tracing bone marrow-derived microglia in brain metastatic tumors.

Microglia are the resident macrophages in the central nervous system (CNS), and they constitute 15-20% of the total glial populations. They have wide developmental and protective functions during brain injury, infection and tumorigenesis. Originally thought to derive from postnatal hematopoietic progenitors, it has recently been demonstrated that microglia originate from primitive myeloid progenitor cells that arise during early development from the embryonic yolk sac.

Regulatory T Cells Control the Switch From to Invasive Breast Cancer.

Ductal carcinoma (DCIS) is a non-obligate precursor of breast cancer, and it only progresses to invasive breast cancer in around 40% of patients. While immune infiltrates have been observed in these early cancer lesions, their potential prognostic value is still unclear. Regulatory T (Treg) cells accumulate in advanced breast cancers, and predict poor outcome.

Preexisting Commensal Dysbiosis Is a Host-Intrinsic Regulator of Tissue Inflammation and Tumor Cell Dissemination in Hormone Receptor-Positive Breast Cancer.

It is unknown why some patients with hormone receptor-positive (HR) breast cancer present with more aggressive and invasive disease. Metastatic dissemination occurs early in disease and is facilitated by cross-talk between the tumor and tissue environment, suggesting that undefined host-intrinsic factors enhance early dissemination and the probability of developing metastatic disease. Here, we have identified commensal dysbiosis as a host-intrinsic factor associated with metastatic dissemination.

Tumor-Associated Macrophage Isolation and In Vivo Analysis of Their Tumor-Promoting Activity.

Characterization of individual cell populations from the tumor microenvironment is critical to understand their functional contribution to tumor progression. Magnetic bead enrichment and fluorescence-activated cell sorting (FACS) allow for the isolation of specific cell types that can be used in downstream applications, including in vitro and in vivo functional studies and molecular profiling. In this chapter, we describe the process of isolation of tumor-associated macrophages (TAMs) from primary murine breast tumors subsequent to therapeutic or experimental intervention.