Prostate luminal cell plasticity and cancer.

Cellular plasticity in prostate cancer promotes treatment resistance. Several independent studies have used mouse models, single-cell RNA sequencing, and genetic lineage tracing approaches to characterize cellular differentiation and plasticity during prostate organogenesis, homeostasis and androgen-mediated tissue regeneration. We review these findings and recent work using immune-competent genetically-engineered mouse models to characterize cellular plasticity and clonal dynamic changes during prostate cancer progression.

A T cell receptor specific for an HLA-A*03:01-restricted epitope in the endogenous retrovirus ERV-K-Env exhibits limited recognition of its cognate epitope.

Transposable elements (TEs) are often expressed at higher levels in tumor cells than normal cells, implicating these genomic regions as an untapped pool of tumor-associated antigens. In ovarian cancer (OC), protein from the TE ERV-K is frequently expressed by tumor cells. Here we determined whether the targeting of previously identified epitope in the envelope gene (env) of ERV-K resulted in target antigen specificity against cancer cells.

T-cell Responses to Individualized Neoantigen Therapy mRNA-4157 (V940) Alone or in Combination with Pembrolizumab in the Phase 1 KEYNOTE-603 Study.

mRNA-4157 (V940) is an individualized neoantigen therapy targeting up to 34 patient-specific tumor neoantigens to induce T-cell responses and potentiate antitumor activity. We report mechanistic insights into the immunogenicity of mRNA-4157 via characterization of T-cell responses to neoantigens from the first-in-human, phase 1, KEYNOTE-603 study (NCT03313778) in patients with resected non-small cell lung cancer (Part A: 1-mg mRNA-4157, n = 4) or resected cutaneous melanoma (Part D: 1-mg mRNA-4157 + 200-mg pembrolizumab, n = 12). Safety, tolerability, and immunogenicity were assessed.

Macrophages of multiple hematopoietic origins reside in the developing prostate.

Tissue-resident macrophages contribute to the organogenesis of many tissues. Growth of the prostate is regulated by androgens during puberty, yet androgens are considered immune suppressive. In this study, we characterized the localization, androgen receptor expression and hematopoietic origin of prostate macrophages, and transiently ablated macrophages during postnatal prostate organogenesis in the mouse.

The association between a patient-centered quality of care index and self-efficacy among cancer survivors.

Purpose: The number of cancer survivors in the US surpassed 18.1 million in 2022 and this number continues to grow. Patient self-efficacy, a patient's confidence in his or her ability to self-manage symptoms and healthcare concerns, has been linked to improved health outcomes.

Durvalumab in combination with chemoradiotherapy in patients with head and neck squamous cell carcinoma: Results from the Phase 1 CLOVER study.

Background: The Phase 1 CLOVER study (NCT03509012) assessed durvalumab in combination with concurrent chemoradiotherapy (cCRT) in patients with advanced solid tumors; we report results from the head and neck squamous cell carcinoma (HNSCC) cohort.

Methods: Patients with histologically/cytologically confirmed locally advanced HNSCC, eligible for definitive cCRT and not considered for primary surgery, received durvalumab plus cisplatin and concurrent external beam radiation. Objectives were to assess safety/tolerability and preliminary efficacy.

Fixed and random effect selections in generalized linear mixed models.

Generalized linear mixed models are commonly used to describe relationships between correlated responses and covariates in medical research. In this paper, we propose a simple and easily implementable regularized estimation approach to select both fixed and random effects in generalized linear mixed model. Specifically, we propose to construct and optimize the objective functions using the confidence distributions of model parameters, as opposed to using the observed data likelihood functions, to perform effect selections.

Biological Functions of the KDM2 Family of Histone Demethylases.

The histone lysine demethylase 2 (KDM2) family of α-Ketoglutarate-Fe-dependent dioxygenases were the first Jumonji-domain-containing proteins reported to harbor demethylase activity. This landmark discovery paved the way for the characterization of more than 25 enzymes capable of demethylating lysine residues on histones-an epigenetic modification previously thought to be irreversible. The KDM2 family is comprised of KDM2A and KDM2B which share significant structural similarities and demethylate lysine 36 on histone H3.

A phase II study of bevacizumab and temsirolimus in advanced extra-pancreatic neuroendocrine tumors.

We assessed the efficacy and safety of combining bevacizumab with temsirolimus in patients with advanced extra-pancreatic neuroendocrine tumors. This NCI-sponsored multicenter, open-label, phase II study (NCT01010126) enrolled patients with advanced, recurrent, or metastatic extra-pancreatic neuroendocrine tumors. All patients were treated with temsirolimus and bevacizumab until disease progression or unacceptable toxicity.

Development of a cervical cancer prevention text-messaging program for women living with HIV.

Cervical cancer screening and human papillomavirus (HPV) vaccination are critical for those immunocompromised due to human immunodeficiency virus (HIV). Health education programs, including text messaging, can effectively improve knowledge of cervical cancer and recommended screening. This paper describes the data-driven development of a 4-week text-messaging intervention to improve HPV and cervical cancer knowledge among women living with HIV (WLH).

Priming a vascular-selective cytokine response permits CD8 T-cell entry into tumors.

Targeting DNA methyltransferase 1 (DNMT1) has immunomodulatory and anti-neoplastic activity, especially when paired with cancer immunotherapies. Here we explore the immunoregulatory functions of DNMT1 in the tumor vasculature of female mice. Dnmt1 deletion in endothelial cells (ECs) impairs tumor growth while priming expression of cytokine-driven cell adhesion molecules and chemokines important for CD8 T-cell trafficking across the vasculature; consequently, the efficacy of immune checkpoint blockade (ICB) is enhanced.

Epigenetically programmed resistance to chemo- and immuno-therapies.

Resistance to cancer treatments remains a major barrier in developing cancer cures. While promising combination chemotherapy treatments and novel immunotherapies have improved patient outcomes, resistance to these treatments remains poorly understood. New insights into the dysregulation of the epigenome show how it promotes tumor growth and resistance to therapy.

Industry marketing of tobacco products on social media: case study of Philip Morris International's IQOS.

Significance: Newer tobacco products might be particularly likely to use social media as they emerge in the global market. Little is known about the official use of social media in marketing heated tobacco products (HTPs). This study examined Philip Morris International's (PMI) social media marketing globally of its leading HTP, IQOS.

TRIM28 promotes luminal cell plasticity in a mouse model of prostate cancer.

The Tripartite motif-containing 28 (TRIM28) transcriptional cofactor is significantly upregulated in high-grade and metastatic prostate cancers. To study the role of TRIM28 in prostate cancer progression in vivo, we generated a genetically-engineered mouse model, combining prostate-specific inactivation of Trp53, Pten and Trim28. Trim28 inactivated NPp53T mice developed an inflammatory response and necrosis in prostate lumens.

Inhibiting DNA methylation and RNA editing upregulates immunogenic RNA to transform the tumor microenvironment and prolong survival in ovarian cancer.

Background: Novel therapies are urgently needed for ovarian cancer (OC), the fifth deadliest cancer in women. Preclinical work has shown that DNA methyltransferase inhibitors (DNMTis) can reverse the immunosuppressive tumor microenvironment in OC. Inhibiting DNA methyltransferases activate transcription of double-stranded (ds)RNA, including transposable elements.

Immunoarray Measurements of Parathyroid Hormone-Related Peptides Combined with Other Biomarkers to Diagnose Aggressive Prostate Cancer.

Parathyroid hormone-related peptide (PTHrP) is related to bone metastasis and hypercalcemia in prostate and breast cancers and should be an excellent biomarker for aggressive forms of these cancers. Current clinical detection protocols for PTHrP are immunoradiometric assay and radioimmunoassay but are not sensitive enough to detect PTHrPs at early stages. We recently evaluated a prostate cancer biomarker panel, including serum monocyte differentiation antigen (CD-14), ETS-related gene protein, pigment epithelial-derived factor, and insulin-like growth factor-1, with promise for identifying aggressive prostate cancers.

Oncology provider experiences during the COVID-19 pandemic.

Purpose: The COVID-19 pandemic upended nearly all aspects of daily life and of medical care, placing a double burden of professional and personal concerns on those who provide medical care. We set out to assess the burden of the pandemic on provider outlook and understand how cancer survivorship providers experienced rapid changes to practice.

Methods: We distributed a survey through the American College of Surgeons Commission on Cancer (CoC) to its accredited organizations in mid-October 2020.

Building implementation science capacity among practitioners of cancer control: development of a pilot training curriculum.

Purpose: Cancer control interventions are difficult to implement with fidelity, while tailoring to fit contexts. Engaged approaches are suggested to advance equity. On-the-ground practitioners are needed to serve as collaborators in the implementation process with research teams, but few trainings are designed with them in mind.

E-cigarette and combusted tobacco abstinence among young adults: Secondary analyses from a U.S.-based randomized controlled trial of vaping cessation.

Objective: To examine patterns of abstinence from e-cigarettes, combusted tobacco products (CTPs), both, or neither among young adults enrolled in a U.S.-based randomized trial of a text message vaping cessation intervention.