Integrating priorities at the intersection of cancer and neuroscience.

Cancer neuroscience is a rapidly growing multidisciplinary field that conceptualizes tumors as tissues fully integrated into the nervous system. Recognizing the complexity and challenges in this field is of fundamental importance to achieving the goal of translational impact for cancer patients. Our commentary highlights key scientific priorities, optimal training settings, and roadblocks to translating scientific findings to the clinic in this emerging field, aiming to formulate a transformative and cohesive path forward.

Perceived comfort with weight, body shape and eating pattern of young adults with type 1 diabetes and associations with clinical and psychological parameters in a clinical setting.

Background: Higher prevalence of disordered eating in young adults with type 1 diabetes (T1D) culminates in higher levels of morbidity and mortality. In addition to validated questionnaires for diabetes distress, depression/anxiety symptoms and emotional well-being, the Diabetes Psychosocial Assessment Tool (DPAT) includes three questions about comfort with weight, body shape and eating pattern (WSE), which were derived from literature and multidisciplinary team consensus. Recognising individuals with low comfort with WSE, is the first step towards identifying those who may be at risk of developing eating disorders.

Neuroimmune cell interactions and chronic infections in oral cancers.

Inflammation is a process that is associated with the activation of distal immunosuppressive pathways that have evolved to restore homeostasis and prevent excessive tissue destruction. However, long-term immunosuppression resulting from systemic and local inflammation that may stem from dysbiosis, infections, or aging poses a higher risk for cancers. Cancer incidence and progression dramatically increase with chronic infections including HIV infection.

Reduced exercise capacity occurs before intrinsic skeletal muscle dysfunction in experimental rat models of pulmonary hypertension.

Reduced exercise capacity in pulmonary hypertension (PH) significantly impacts quality of life. However, the cause of reduced exercise capacity in PH remains unclear. The objective of this study was to investigate whether intrinsic skeletal muscle changes are causative in reduced exercise capacity in PH using preclinical PH rat models with different PH severity.

HPV-associated oropharyngeal cancer: in search of surrogate biomarkers for early lesions.

The incidence of oropharyngeal cancer (OPSCC) has escalated in the past few decades; this has largely been triggered by high-risk human papillomavirus (HPV). Early cancer screening is needed for timely clinical intervention and may reduce mortality and morbidity, but the lack of knowledge about premalignant lesions for OPSCC poses a significant challenge to early detection. Biomarkers that identify individuals at high risk for OPSCC may act as surrogate markers for precancer but these are limited as only a few studies decipher the multistep progression from HPV infection to OPSCC development.

Salivary microbiome changes distinguish response to chemoradiotherapy in patients with oral cancer.

Background: Oral squamous cell carcinoma (SCC) is associated with oral microbial dysbiosis. In this unique study, we compared pre- to post-treatment salivary microbiome in patients with SCC by 16S rRNA gene sequencing and examined how microbiome changes correlated with the expression of an anti-microbial protein.

Results: Treatment of SCC was associated with a reduction in overall bacterial richness and diversity.

Clinical, morphologic and molecular heterogeneity of HPV-associated oropharyngeal cancer.

The incidence of human papillomavirus-positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) is rising rapidly and has exceeded cervical cancer to become the most common HPV-induced cancer in developed countries. Since patients with HPV + OPSCC respond very favorably to standard aggressive treatment, the emphasis has changed to reducing treatment intensity. However, recent multi-center clinical trials failed to show non-inferiority of de-escalation strategies on a population basis, highlighting the need to select low-risk patients likely to respond to de-intensified treatments.

Whole-genome CpG-resolution DNA Methylation Profiling of HNSCC Reveals Distinct Mechanisms of Carcinogenesis for Fine-scale HPV+ Cancer Subtypes.

Unlabelled: DNA methylation is a vital early step in carcinogenesis. Most findings of aberrant DNA methylation in head and neck squamous cell carcinomas (HNSCC) are array based with limited coverage and resolution, and mainly explored by human papillomavirus (HPV) status, ignoring the high heterogeneity of this disease. In this study, we performed whole-genome bisulfite sequencing on a well-studied HNSCC cohort ( = 36) and investigated the methylation changes between fine-scaled HNSCC subtypes in relation to genomic instability, repetitive elements, gene expression, and key carcinogenic pathways.

An emerging field: An evaluation of biomedical graduate student and postdoctoral education and training research across seven decades.

Biomedical graduate student and postdoctoral education and training research has expanded greatly over the last seven decades, leading to increased publications and the emergence of a field. The goal of this study was to analyze this growth by performing a cross-sectional bibliometric analysis using a systematic approach to better understand the publishing trends (including historical vs. emerging themes and research priorities); depth, structure, and evidence-basis of content; and venues for publication.

Emotional well-being and HbA1c following the implementation of the Diabetes Psychosocial Assessment Tool (DPAT) in young adults with type 1 diabetes (T1DM): An observational study.

Aims: This observational study evaluated the implementation of the Diabetes Psychosocial Assessment Tool (DPAT), assessing emotional well-being of young adults with type 1 diabetes (T1DM) and the clinical congruency between DPAT-recommended and specialist-led referrals.

Methods: Young adults with T1DM attending the clinic completed the DPAT on two occasions. The DPAT includes the PAID (diabetes distress), PHQ-4 (depression/anxiety) and WHO-5 (general well-being), a diabetes health audit and a referral pathway to (allied) health professionals.

Increased Nerve Density Adversely Affects Outcome in Oral Cancer.

Purpose: Perineural invasion (PNI) in oral cavity squamous cell carcinoma (OSCC) is associated with poor survival. Because of the risk of recurrence, patients with PNI receive additional therapies after surgical resection. Mechanistic studies have shown that nerves in the tumor microenvironment promote aggressive tumor growth.

The 3D's of Neural Phenotypes in Oral Cancer: Distance, Diameter, and Density.

Squamous cell carcinoma of the oral cavity (OSCC) is the most common type of head and neck cancer; survival is poor, and response to treatment varies. Metastasis or recurrence in the regional lymph nodes is associated with poor survival. Consequently, overt or occult spread to the lymph nodes is used to identify patients who will receive adjuvant radiation therapy.

Agenda-setting by young adults with type 1 diabetes and associations with emotional well-being/social support: results from an observational study.

Background: The Diabetes Psychosocial Assessment Tool (DPAT) was developed to assess the psychosocial well-being of young adults with type 1 diabetes in clinical practice. The DPAT includes three validated questionnaires (assessing diabetes distress, anxiety/depressive symptoms and emotional well-being) and an agenda-setting tool. It is currently used by the Queensland Statewide Diabetes Clinical Network (available at Clinical Excellence Queensland).

Spatial and Transcriptomic Analysis of Perineural Invasion in Oral Cancer.

Purpose: Perineural invasion (PNI), a common occurrence in oral squamous cell carcinomas, is associated with poor survival. Consequently, these tumors are treated aggressively. However, diagnostic criteria of PNI vary and its role as an independent predictor of prognosis has not been established.

Galanin mediates tumor-induced immunosuppression in head and neck squamous cell carcinoma.

Purpose: Galanin receptor 2 (GALR2) plays a significant role in the progression of head and neck squamous cell carcinomas (HNSCC). Since there is virtually no information on immunomodulation mediated by its ligand in the tumor microenvironment, we assessed the effects of galanin on peripheral blood mononuclear cells (PBMCs).

Methods: After verification of GALR2 expression and it activity in PBMCs we evaluated the effect of galanin and conditioned media from HNSCC cell lines silenced for galanin or antibody-depleted, on proliferation, apoptosis, cytokine expression and activation/differentiation of immune cells.

Nerve density in cancer: Less is better.

The density of nerves in cancer is emerging as a relevant clinical parameter for patient survival. Nerves in the tumor microenvironment have been associated with poor survival and recurrence, particularly if involved in perineural invasion. However, usually only a few nerves inside a tumor are affected by perineural invasion, while most nerves are not.

Cancer-associated keratinocytes: new members of the microenvironment in head and neck cancer.

The tumor microenvironment is a complex ecosystem of malignant and nonmalignant cells and extracellular proteins that work together to enhance tumor progression. We identified a mechanism in which adjacent nonmalignant epithelium enhances invasion of squamous cell carcinoma, thereby expanding the tumor microenvironment to include cancer-associated keratinocytes.

T-Cell Expression and Release of Kidney Injury Molecule-1 in Response to Glucose Variations Initiates Kidney Injury in Early Diabetes.

Half of the mortality in diabetes is seen in individuals <50 years of age and commonly predicted by the early onset of diabetic kidney disease (DKD). In type 1 diabetes, increased urinary albumin-to-creatinine ratio (uACR) during adolescence defines this risk, but the pathological factors responsible remain unknown. We postulated that early in diabetes, glucose variations contribute to kidney injury molecule-1 (KIM-1) release from circulating T cells, elevating uACR and DKD risk.

Phosphorylation of TRIP13 at Y56 induces radiation resistance but sensitizes head and neck cancer to cetuximab.

Radiation therapy, a mainstay of treatment for head and neck cancer, is not always curative due to the development of treatment resistance; additionally, multi-institutional trials have questioned the efficacy of concurrent radiation with cetuximab, the epidermal growth factor receptor (EGFR) inhibitor. We unraveled a mechanism for radiation resistance; that is, radiation induces EGFR, which phosphorylates TRIP13 (thyroid hormone receptor interactor 13) on tyrosine 56. Phosphorylated (phospho-)TRIP13 promotes non-homologous end joining (NHEJ) repair to induce radiation resistance.