A phase I study of docetaxel plus synthetic lycopene in metastatic prostate cancer patients.

Purpose: Our preclinical studies showed that lycopene enhanced the anti-prostate cancer efficacy of docetaxel in animal models. A phase I trial (NCT0149519) was conducted to identify an optimum dose of synthetic lycopene in combination with docetaxel (and androgen blockade [androgen deprivation therapy, ADT]), and to evaluate its effect on the safety and pharmacokinetics of docetaxel in men with metastatic prostate cancer.

Methods: Subjects were treated with 21-day cycles of 75 mg/m docetaxel (and ADT), plus lycopene at 30, 90 or 150 mg/day.

Quantifying Oropharyngeal Swallowing Impairment in Response to Bolus Viscosity.

Purpose: The purpose of this study was to test the feasibility for quantifying changes in oropharyngeal swallowing impairment in response to alteration in bolus viscosity using a reliable and valid method of observational measurement-the Modified Barium Swallow Impairment Profile (MBSImP).

Method: This retrospective analysis included a heterogeneous cohort of 119 patients with suspected dysphagia that underwent a videofluoroscopic swallowing study as part of clinical care. Using consensus scoring, two expert clinicians assigned MBSImP scores to components related to oropharyngeal swallowing function between two bolus viscosities (thin liquid and pudding): epiglottic movement, laryngeal elevation, anterior hyoid excursion, tongue base retraction, pharyngeal stripping wave, and pharyngoesophageal segment opening (PESO).

Relating Physiologic Swallowing Impairment, Functional Swallowing Ability, and Swallow-Specific Quality of Life.

Many studies include functional swallowing ability and quality of life information to indicate a response to a specific swallowing intervention or to describe the natural history of dysphagia across diseases and conditions. Study results are difficult to interpret because the association between these factors and actual swallowing impairment is not understood. We set out to test the associations between components of physiologic swallowing impairment, functional swallowing ability, and swallow-specific quality of life using standardized and validated measurement tools: Modified Barium Swallow Impairment Profile (MBSImP), Functional Oral Intake Scale (FOIS), Eating Assessment Tool (EAT-10), and Dysphagia Handicap Index (DHI).

A pilot randomized controlled trial to evaluate a survivorship care planning intervention for head and neck cancer survivor-caregiver dyads.

Purpose: Head and neck cancer (HNC) survivors and caregivers face significant challenges after treatment. This study's objective was to evaluate the effects of a dyadic survivorship care planning (SCP) intervention on survivor and caregiver outcomes.

Methods: This randomized controlled trial enrolled HNC survivors and caregivers within 18 months post-treatment, randomized dyads to SCP (one-session with written SCP and follow-up telephone call) or usual care and administered baseline and 6-month surveys.

SWAN pathway-network identification of common aneuploidy-based oncogenic drivers.

Haploinsufficiency drives Darwinian evolution. Siblings, while alike in many aspects, differ due to monoallelic differences inherited from each parent. In cancer, solid tumors exhibit aneuploid genetics resulting in hundreds to thousands of monoallelic gene-level copy-number alterations (CNAs) in each tumor.

Neoadjuvant presurgical PD-1 inhibition in oral cavity squamous cell carcinoma.

Oral cavity squamous cell carcinoma (OCSCC) is a prevalent surgically treated subset of head and neck cancer with frequent recurrence and poor survival. Immunotherapy has demonstrated efficacy in recurrent/metastatic head and neck cancer. However, whether antitumor responses could be fostered by neoadjuvant presurgical immunotherapy remains unclear.

A single strain of Bacteroides fragilis protects gut integrity and reduces GVHD.

Graft-versus-host disease (GVHD) is a pathological process caused by an exaggerated donor lymphocyte response to host antigens after allogeneic hematopoietic cell transplantation (allo-HCT). Donor T cells undergo extensive clonal expansion and differentiation, which culminate in damage to recipient target organs. Damage to the gastrointestinal tract is a main contributor to morbidity and mortality.

Respiratory-swallow coordination and swallowing impairment in head and neck cancer.

Background: The aim of the study was to determine the link between frequency of optimal respiratory-swallow coordination, swallowing impairment, and airway invasion in head and neck cancer (HNC) patients.

Method: A cross-sectional study of a heterogeneous group of HNC patients (49), precancer (N = 30) or postcancer treatment (N = 29), participated in a single Modified Barium Swallow Study (MBSS) with synchronized respiratory data.

Results: Spearman correlation coefficients revealed significant negative correlations between optimal respiratory-swallow phase pattern and objective measures of swallowing impairment: penetration-aspiration scale max, pharyngeal total, and oral total scores with Spearman correlation coefficients of -0.

Identification of human CD4 T cell populations with distinct antitumor activity.

How naturally arising human CD4 T helper subsets affect cancer immunotherapy is unclear. We reported that human CD4CD26 T cells elicit potent immunity against solid tumors. As CD26 T cells are often categorized as T17 cells for their IL-17 production and high CD26 expression, we posited these populations would have similar molecular properties.

Development and implementation of the SUM breast cancer cell line functional genomics knowledge base.

Several years ago, the SUM panel of human breast cancer cell lines was developed, and these cell lines have been distributed to hundreds of labs worldwide. Our lab and others have developed extensive omics data sets from these cells. More recently, we performed genome-scale shRNA essentiality screens on the entire SUM line panel, as well as on MCF10A cells, MCF-7 cells, and MCF-7LTED cells.

Neuropilin-2b facilitates resistance to tyrosine kinase inhibitors in non-small cell lung cancer.

Objective: Innate and acquired resistance is the principle factor limiting the efficacy of tyrosine kinase inhibitors in lung cancer. We have observed a dramatic upregulation of the cell surface co-receptor neuropilin-2b in lung cancers clinically treated with tyrosine kinase inhibitors correlating with acquired resistance. We hypothesize that neuropilin-2b plays a functional role in acquired tyrosine kinase inhibitor resistance.

Classification of Physiologic Swallowing Impairment Severity: A Latent Class Analysis of Modified Barium Swallow Impairment Profile Scores.

Purpose Our objectives were to (a) identify oral and pharyngeal physiologic swallowing impairment severity classes based on latent class analyses (LCAs) of the Modified Barium Swallow Impairment Profile (MBSImP) swallow task scores and (b) quantify the probability of severity class membership given composite MBSImP oral total (OT) and pharyngeal total (PT) scores. Method MBSImP scores were collected from a patient database of 319 consecutive modified barium swallow studies. Because of missing swallow task scores, LCA was performed using 25 multiply imputed data sets.

IL6 Fuels Durable Memory for Th17 Cell-Mediated Responses to Tumors.

The accessibility of adoptive T-cell transfer therapies (ACT) is hindered by the cost and time required for product development. Here we describe a streamlined ACT protocol using Th17 cells expanded only 4 days . While shortening expansion compromised cell yield, this method licensed Th17 cells to eradicate large tumors to a greater extent than cells expanded longer term.

Immunological effects of nivolumab immunotherapy in patients with oral cavity squamous cell carcinoma.

Background: Although checkpoint blockades have become widely used, the immunological impact in cancer patients, especially those with oral cavity squamous cell carcinoma (OCSCC), has not been well studied.

Methods: The present study assessed the immunological impact of anti-PD-1 (nivolumab) treatment in 10 patients with OCSCC. This involved phenotypic analyses of peripheral blood T-cell subpopulations and their expression of immune mediators prior to and following nivolumab treatment.

Aging Effects on Eating Assessment Tool-10 (EAT-10) Total Scores in Healthy, Community-Dwelling Adults.

The purpose of this study was to examine how aging and sex impacted scores on the Eating Assessment Tool-10 in a large sample of healthy, non-dysphagic adults. Differences in Eating Assessment Tool-10 total normal (< 3) and abnormal (≥ 3) scores were examined across four age categories (21-39 years, 40-59 years, 60-79 years, 80 years and older) and between sexes. The mean (± ) Eating Assessment Tool-10 total score for this healthy cohort of 167 individuals was 0.

Polo-like kinase 1 (Plk1) inhibition synergizes with taxanes in triple negative breast cancer.

Within triple negative breast cancer, several molecular subtypes have been identified, underlying the heterogeneity of such an aggressive disease. The basal-like subtype is characterized by mutations in the TP53 gene, and is associated with a low pathologic complete response rate following neoadjuvant chemotherapy. In a genome-scale short hairpin RNA (shRNA) screen of breast cancer cells, polo-like kinase 1 (Plk1) was a frequent and strong hit in the basal breast cancer cell lines indicating its importance for growth and survival of these breast cancer cells.

HUNK phosphorylates EGFR to regulate breast cancer metastasis.

Epidermal growth factor receptor (EGFR) is commonly over-expressed in metastatic breast cancer yet metastatic breast cancer is generally resistant to anti-EGFR therapies, and the mechanism for resistance to EGFR inhibitors in this setting is not fully understood. Hormonally up-regulated neu-associated kinase (HUNK) kinase is up-regulated in aggressive breast cancers and is thought to play a role in breast cancer metastasis. However, no studies have been conducted to examine a relationship between EGFR and HUNK in breast cancer metastasis.

Hematology and Depression Levels: Examining Correlated Factors Among Hospitalized Patients.

Background: Depression in patients with cancer negatively influences physical symptoms, treatment success, coping, and quality of life (QOL), and is associated with increased mortality.

Objectives: This study investigated the prevalence of depression and explored fatigue, QOL, and pain that is associated with depression in patients on first admission to a hematologic oncology unit.

Methods: This descriptive study measured depression, QOL, and fatigue with the Patient Health Questionnaire-9, the Functional Assessment of Cancer Therapy (FACT)-General, and the FACT-Anemia scale, respectively.

Eukaryotic initiation factor 4E-binding protein as an oncogene in breast cancer.

Background: Eukaryotic Initiation Factor 4E-Binding Protein (EIF4EBP1, 4EBP1) is overexpressed in many human cancers including breast cancer, yet the role of 4EBP1 in breast cancer remains understudied. Despite the known role of 4EBP1 as a negative regulator of cap-dependent protein translation, 4EBP1 is predicted to be an essential driving oncogene in many cancer cell lines in vitro, and can act as a driver of cancer cell proliferation. EIF4EBP1 is located within the 8p11-p12 genomic locus, which is frequently amplified in breast cancer and is known to predict poor prognosis and resistance to endocrine therapy.

Syringotropic Mycosis Fungoides: A Variant of Folliculotropic Mycosis Fungoides or a Distinct Entity?

Syringotropic mycosis fungoides (MF) is classified under folliculotropic MF. Although there is significant overlap between the 2, this study demonstrates that folliculotropism is frequently present in syringotropic MF, and when not present, the specimen did not include a follicle to examine. In addition, few of the pathology reports mentioned folliculotropism or syringotropism, although this is an important prognostic feature.

Bolus Airway Invasion Observed During Videofluoroscopy in Healthy, Non-dysphagic Community-Dwelling Adults.

Objectives: Typical aging may result in subclinical swallowing alterations (presbyphagia), which can place an individual at risk for dysphagia-related conditions, such as aspiration pneumonia, secondary to loss of functional reserve and rising incidence of age-related diseases associated with dysphagia. The purpose of this study was to investigate occurrence of airway invasion among healthy, nondysphagic community-dwelling adults. Further, we tested for differences of airway invasion across age categories and between sexes.

Evaluation of a survivorship needs assessment planning tool for head and neck cancer survivor-caregiver dyads.

Purpose: The objectives of this study were to test the acceptability and feasibility of a survivorship needs assessment planning (SNAP) tool for head and neck cancer (HNC) survivors and caregivers, evaluate short-term changes in psychosocial outcomes after completing the SNAP session, and develop strategies for system refinement.

Methods: We used a prospective one-group design and mixed methods with HNC survivors and caregivers (N = 25 dyads). Participants completed baseline and 6-week surveys before and after completing a SNAP clinic visit to assess psychosocial outcomes and acceptability.

Staurosporine, an inhibitor of hormonally up-regulated neu-associated kinase.

HUNK is a protein kinase that is implicated in HER2-positive (HER2+) breast cancer progression and resistance to HER2 inhibitors. Though prior studies suggest there is therapeutic potential for targeting HUNK in HER2+ breast cancer, pharmacological agents that target HUNK are yet to be identified. A recent study showed that the broad-spectrum kinase inhibitor staurosporine binds to the HUNK catalytic domain, but the effect of staurosporine on HUNK enzymatic activity was not tested.