Quantitative proteomic analysis of HER2 protein expression in PDAC tumors.

Metastatic pancreatic adenocarcinoma (PDAC) is the third leading cause of cancer-related death in the United States, with a 5-year survival rate of only 11%, necessitating identification of novel treatment paradigms. Tumor tissue specimens from patients with PDAC, breast cancer, and other solid tumor malignancies were collected and tumor cells were enriched using laser microdissection (LMD). Reverse phase protein array (RPPA) analysis was performed on enriched tumor cell lysates to quantify a 32-protein/phosphoprotein biomarker panel comprising known anticancer drug targets and/or cancer-related total and phosphorylated proteins, including HER2, HER2, and HER3.

Integration of Multi-omic Data in a Molecular Tumor Board Reveals EGFR-Associated ALK-Inhibitor Resistance in a Patient With Inflammatory Myofibroblastic Cancer.

Inflammatory myofibroblastic tumors (IMTs) are intermediate-grade mesenchymal neoplasms commonly characterized by chromosomal rearrangements causing constitutive activation of anaplastic lymphoma kinase (ALK) and/or ALK mutations causing reduced sensitivity to ALK tyrosine kinase inhibitors (TKI). We present a patient with an IMT who initially responded to first-line alectinib, but who later suffered disease relapse and presently survives with moderate residual disease after receiving second-line lorlatinib. Biopsy specimens were analyzed using next generation sequencing (DNA-seq and RNA-seq) and reverse phase protein microarray (RPPA) as part of an institutional Molecular Tumor Board (MTB) study.

Effectiveness of an Electronic Medical Record-Based Recognition Tool for the Identification of Incidental Pulmonary Nodules.

Background: Incidental pulmonary nodules (IPNs) are lung nodules detected on imaging studies performed for an unrelated reason. Approximately 1.6 million IPNs are detected in the United States every year.

Safety of Nivolumab Added to Chemoradiation Therapy Platforms for Intermediate and High-Risk Locoregionally Advanced Head and Neck Squamous Cell Carcinoma: RTOG Foundation 3504.

Purpose: Programmed death-1 immune checkpoint blockade improves survival of patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), but the benefits of addition to (chemo)radiation for newly diagnosed patients with HNSCC remain unknown.

Methods And Materials: We evaluated the safety of nivolumab concomitant with 70 Gy intensity modulated radiation therapy and weekly cisplatin (arm 1), every 3-week cisplatin (arm 2), cetuximab (arm 3), or alone for platinum-ineligible patients (arm 4) in newly diagnosed intermediate- or high-risk locoregionally advanced HNSCC. Patients received nivolumab from 2 weeks prior to radiation therapy until 3 months post-radiation therapy.

Safety and Tolerability of Carboplatin and Paclitaxel in Cancer Patients with HIV (AMC-078), an AIDS Malignancy Consortium (AMC) Study.

Background: Persons living with human immunodeficiency virus are an underserved population for evidence-based cancer treatment. Paclitaxel and carboplatin (PCb) is an active regimen against a variety of solid tumors, including several seen in excess in patients with HIV infection. We performed a pilot trial to evaluate the safety of full-dose PCb in people living with human immunodeficiency virus and cancer.

Remote Home Monitoring of Patients With Cancer During the COVID Pandemic: A Pilot Study.

Purpose: The COVID-19 pandemic has posed significant challenges in the care of patients with cancer, including how to manage outpatients who are COVID-positive but do not require hospitalization. We explored the use of a remote patient monitoring (RPM) program to care for such outpatients.

Methods: Consecutive patients who were tested for COVID-19 because of symptom onset but were clinically stable were offered enrollment into a pilot RPM program.

A phase I trial of the mTOR inhibitor temsirolimus in combination with capecitabine in patients with advanced malignancies.

Background: Temsirolimus is an mTOR antagonist with proven anticancer efficacy. Preclinical data suggest greater anticancer effect when mTOR inhibitors are combined with cytotoxic chemotherapy. We performed a Phase I assessment of the combination of temsirolimus and capecitabine in patients with advanced solid tumors.

Gut microbial composition difference between pediatric ALL survivors and siblings.

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer with high cure rates leading to rising numbers of long-term survivors. Adult survivors of childhood ALL are at increased risk of obesity, cardiovascular disease, and other chronic illnesses. We hypothesize that ALL therapy is associated with long-term gut microbiome alterations that contribute to predisposition to chronic medical conditions.

Studying the urine microbiome in superficial bladder cancer: samples obtained by midstream voiding versus cystoscopy.

Background: Preliminary data suggest that the urinary microbiome may play a role in bladder cancer. Information regarding the most suitable method of collecting urine specimens is needed for the large population studies needed to address this. To compare microbiome metrics resulting from 16S ribosomal RNA gene sequencing between midstream, voided specimens and those obtained at cystoscopy.

Association of Ancestral Genetic Admixture and Excess Weight at Twelve Months of Age.

Understanding the influence of genetically determined ancestry may give insight into the disparities of obesity seen in different ethnic groups beginning at a very early age. To investigate the relationship between children's ancestral genetic proportions and excess weight at 12 months of age. Eight hundred twenty-one 12-month-old children were included in this cross-sectional study.

A phase I study of HER1, HER2 dual kinase inhibitor lapatinib plus the proteasome inhibitor bortezomib in patients with advanced malignancies.

Purpose: This phase I trial evaluated the maximum tolerated dose, safety and preliminary efficacy of lapatinib, a HER1, HER2 dual kinase inhibitor plus bortezomib, a proteasome inhibitor, in adult patients with advanced malignancies.

Methods: Patients were enrolled in a standard 3 + 3 design with lapatinib (L) 750, 1000, 1250 or 1500 mg daily, and bortezomib (B) 0.7, 1.

EPG5 Variants with Modest Functional Impact Result in an Ameliorated and Primarily Neurological Phenotype in a 3.5-Year-Old Patient with Vici Syndrome.

Congenital disorders of autophagy are multisystem disorders with significant neurological involvement. Ectopic p-granules protein 5 ()-associated Vici syndrome is a prototypical congenital disorder of autophagy and presents with the cardinal features of agenesis of the corpus callosum, cataracts, cardiomyopathy, immunodeficiency, and oculocutaneous hypopigmentation. The majority of variants leading to Vici syndrome are null alleles with only a few missense variants published to date.

Genome sequencing analysis of blood cells identifies germline haplotypes strongly associated with drug resistance in osteosarcoma patients.

Background: Osteosarcoma is the most common malignant bone tumor in children. Survival remains poor among histologically poor responders, and there is a need to identify them at diagnosis to avoid delivering ineffective therapy. Genetic variation contributes to a wide range of response and toxicity related to chemotherapy.

Endosomal trafficking defects in patient cells with biallelic variants.

The uncharacterized gene has recently been associated with a congenital neurological malformation disorder that variably presents with arthrogryposis, craniofacial and/or cardiac abnormalities. We have identified two additional patients with compound heterozygous variants presenting with the same neurological malformations. The mechanism whereby KIAA1109 loss of function causes this spectrum of disorders was the primary focus of our studies.

Clinical and social factors associated with excess weight in Hispanic and non-Hispanic White children.

Background: Hispanic children are disproportionately affected by obesity, with this disparity starting at a young age, and there is a paucity of data comparing factors associated with excess weight in the first year of life in Hispanic vs. non-Hispanic populations.

Methods: Excess weight was defined as weight-for-length ≥95th percentile.

Germline de novo mutation clusters arise during oocyte aging in genomic regions with high double-strand-break incidence.

Clustering of mutations has been observed in cancer genomes as well as for germline de novo mutations (DNMs). We identified 1,796 clustered DNMs (cDNMs) within whole-genome-sequencing data from 1,291 parent-offspring trios to investigate their patterns and infer a mutational mechanism. We found that the number of clusters on the maternal allele was positively correlated with maternal age and that these clusters consisted of more individual mutations with larger intermutational distances than those of paternal clusters.

Efficacy of Larotrectinib in TRK Fusion-Positive Cancers in Adults and Children.

Background: Fusions involving one of three tropomyosin receptor kinases (TRK) occur in diverse cancers in children and adults. We evaluated the efficacy and safety of larotrectinib, a highly selective TRK inhibitor, in adults and children who had tumors with these fusions.

Methods: We enrolled patients with consecutively and prospectively identified TRK fusion-positive cancers, detected by molecular profiling as routinely performed at each site, into one of three protocols: a phase 1 study involving adults, a phase 1-2 study involving children, or a phase 2 study involving adolescents and adults.

A phase I study of intravenous artesunate in patients with advanced solid tumor malignancies.

Purpose: The artemisinin class of anti-malarial drugs has shown significant anti-cancer activity in pre-clinical models. Proposed anti-cancer mechanisms include DNA damage, inhibition of angiogenesis, TRAIL-mediated apoptosis, and inhibition of signaling pathways. We performed a phase I study to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of intravenous artesunate (IV AS).

A novel inborn error of the coenzyme Q10 biosynthesis pathway: cerebellar ataxia and static encephalomyopathy due to COQ5 C-methyltransferase deficiency.

Primary coenzyme Q10 (CoQ ; MIM# 607426) deficiencies are an emerging group of inherited mitochondrial disorders with heterogonous clinical phenotypes. Over a dozen genes are involved in the biosynthesis of CoQ , and mutations in several of these are associated with human disease. However, mutations in COQ5 (MIM# 616359), catalyzing the only C-methylation in the CoQ synthetic pathway, have not been implicated in human disease.

Identification of novel SNPs associated with risk and prognosis in patients with castration-resistant prostate cancer.

Aim: Metabolism and transport play major roles in life-long exposure to endogenous and exogenous carcinogens. We therefore explored associations between polymorphisms in absorption, distribution, metabolism and elimination genes and the risk and prognosis of castration-resistant prostate cancer (CRPC).

Materials & Methods: A total of 634 genotypes were tested in 74 patients using the Affymetrix DMETv1.