Characterizing the regulatory Fas (CD95) epitope critical for agonist antibody targeting and CAR-T bystander function in ovarian cancer.

Receptor clustering is the most critical step to activate extrinsic apoptosis by death receptors belonging to the TNF superfamily. Although clinically unsuccessful, using agonist antibodies, the death receptors-5 remains extensively studied from a cancer therapeutics perspective. However, despite its regulatory role and elevated function in ovarian and other solid tumors, another tumor-enriched death receptor called Fas (CD95) remained undervalued in cancer immunotherapy until recently, when its role in off-target tumor killing by CAR-T therapies was imperative.

Documentation of Infertility Risk Discussion in Cancer Patients Receiving Cancer-Directed Therapy: The UC Davis Cancer Center Experience.

A complication of cancer-directed therapy that often goes undiscussed is infertility. Although guidelines recommend addressing the possibility of infertility and fertility preservation approaches before initiating treatment, an internal review at our institution showed only 49% of female patients had infertility risk counseling documented. As a result, a fertility assessment communication was added into all oncology treatment plans to improve rates of fertility discussion and documentation.

Multiple Components of Protein Homeostasis Pathway Can Be Targeted to Produce Drug Synergies with VCP Inhibitors in Ovarian Cancer.

Protein quality control mechanisms play an important role in cancer progression by providing adaptive responses and morphologic stability against genome-wide copy number alterations, aneuploidy, and conformation-altering somatic mutations. This dependency on protein quality control mechanisms creates a vulnerability that may be exploited for therapeutic benefits by targeting components of the protein quality control mechanism. Recently, valosin-containing protein (VCP), also known at p97 AAA-ATPase, has emerged as a druggable target in cancer cells to affect their dependency on protein quality control.

Tetraspanins are unevenly distributed across single extracellular vesicles and bias sensitivity to multiplexed cancer biomarkers.

Background: Tetraspanin expression of extracellular vesicles (EVs) is often used as a surrogate for their detection and classification, a practice that typically assumes their consistent expression across EV sources.

Results: Here we demonstrate that there are distinct patterns in colocalization of tetraspanin expression of EVs enriched from a variety of in vitro and in vivo sources. We report an optimized method for the use of single particle antibody-capture and fluorescence detection to identify subpopulations according to tetraspanin expression and compare our findings with nanoscale flow cytometry.

Short-term organoid culture for drug sensitivity testing of high-grade serous carcinoma.

Objective: Cancer patient-derived organoids (PDOs) grow as three dimensional (3D) structures in the presence of extracellular matrix and have been found to represent the original tumor's genetic complexity. In addition, PDOs can be grown and subjected to drug sensitivity testing in a shorter time course and with lesser expense than patient-derived xenograft models. Many patients with recurrent ovarian cancer develop malignant effusions that become refractory to chemotherapy.

Multiple Reaction Monitoring for the Quantitation of Serum Protein Glycosylation Profiles: Application to Ovarian Cancer.

Protein glycosylation fingerprints are widely recognized as potential markers for disease states, and indeed differential glycosylation has been identified in multiple types of autoimmune diseases and several types of cancer. However, releasing the glycans leave the glycoproteins unknown; therefore, there exists a need for high-throughput methods that allow quantification of site- and protein-specific glycosylation patterns from complex biological mixtures. In this study, a targeted multiple reaction monitoring (MRM)-based method for the protein- and site-specific quantitation involving serum proteins immunoglobulins A, G and M, alpha-1-antitrypsin, transferrin, alpha-2-macroglobulin, haptoglobin, alpha-1-acid glycoprotein and complement C3 was developed.

Optimal perioperative anesthesia management for gynecologic interstitial brachytherapy.

Purpose: To propose an optimal perioperative pain management clinical care pathway for interstitial brachytherapy for gynecologic cancer based on our interdepartmental experience.

Material And Methods: We conducted a retrospective review of 23 women who underwent 32 interstitial brachytherapy procedures for gynecological cancers, analyzing patient demographics, type of anesthetic, medications, postoperative pain scores, adverse events, and delays in discharge. We measured the association of postoperative nausea and/or vomiting (PONV) with hydromorphone use, and postoperative pain scores and total narcotic administration with type of anesthesia.

The Use of Endometrial Cancer Patient-Derived Organoid Culture for Drug Sensitivity Testing Is Feasible.

Objective: Patient-derived organoids (PDOs), used in multiple tumor types, have allowed evaluation of tumor characteristics from individual patients. This study aimed to assess the feasibility of applying PDO in vitro culture for endocrine-based and drug sensitivity testing in endometrial cancer.

Methods: Endometrial cancer cells were enzymatically dissociated from tumors retrieved from fresh hysterectomy specimens and cultured within basement membrane extract in serum-free medium.

Multispectral Optical Tweezers for Biochemical Fingerprinting of CD9-Positive Exosome Subpopulations.

Extracellular vesicles (EVs), including exosomes, are circulating nanoscale particles heavily implicated in cell signaling and can be isolated in vast numbers from human biofluids. Study of their molecular profiling and materials properties is currently underway for purposes of describing a variety of biological functions and diseases. However, the large, and as yet largely unquantified, variety of EV subpopulations differing in composition, size, and likely function necessitates characterization schemes capable of measuring single vesicles.

Factors Predicting Use of Neoadjuvant Chemotherapy Compared With Primary Debulking Surgery in Advanced Stage Ovarian Cancer-A National Cancer Database Study.

Objectives: We performed a patterns-of-care study to characterize the types of patients with epithelial ovarian cancer (EOC) who received neoadjuvant chemotherapy (NACT) versus primary debulking surgery (PDS) using the National Cancer Database (NCDB).

Methods: We identified patients with stages IIIC and IV EOC in the NCDB diagnosed from 2003 to 2011. Patients who received chemotherapy (CT) prior to surgery were classified as receiving NACT; if surgery preceded CT, then it was classified as PDS.

Glycoproteomic Analysis of Malignant Ovarian Cancer Ascites Fluid Identifies Unusual Glycopeptides.

Ovarian cancer is a major cause of cancer mortality among women, largely due to late diagnosis of advanced metastatic disease. More extensive molecular analysis of metastatic ovarian cancer is needed to identify post-translational modifications of proteins, especially glycosylation that is particularly associated with metastatic disease to better understand the metastatic process and identify potential therapeutic targets. Glycoproteins in ascites fluid were enriched by affinity binding to lectins (ConA or WGA) and other affinity matrices.

Refusal of Recommended Chemotherapy for Ovarian Cancer: Risk Factors and Outcomes; a National Cancer Data Base Study.

Objective: To identify risk factors associated with refusal of recommended chemotherapy and its impact on patients with epithelial ovarian cancer (EOC).

Methods: We identified patients in the National Cancer Data Base diagnosed with EOC from January 1998 to December 2011. Patients who refused chemotherapy were identified and compared with those who received recommended, multiagent chemotherapy.

Characteristics of Long-Term Survivors of Epithelial Ovarian Cancer.

Objective: To identify characteristics associated with long-term survival for patients with epithelial ovarian cancer using the California Cancer Registry.

Methods: A descriptive analysis of survival of all California residents diagnosed with epithelial ovarian cancer between 1994 and 2001 was conducted using patients identified through the cancer registry with follow-up through 2011. Characteristics of the patients who survived more than 10 years (long-term survivors) were compared with three other cohorts: patients who survived less than 2 years, those who survived at least 2 but no more than 5 years, and those who survived at least 5 but no more than 10 years.

Evaluation of glycomic profiling as a diagnostic biomarker for epithelial ovarian cancer.

Background: Prior studies suggested that glycans were differentially expressed in patients with ovarian cancer and controls. We hypothesized that glycan-based biomarkers might serve as a diagnostic test for ovarian cancer and evaluated the ability of glycans to distinguish ovarian cancer cases from matched controls.

Methods: Serum samples were obtained from the tissue-banking repository of the Gynecologic Oncology Group, and included healthy female controls (n = 100), women diagnosed with low malignant potential (LMP) tumors (n = 52), and epithelial ovarian cancers (EOC) cases (n = 147).

Accounting for undetected compounds in statistical analyses of mass spectrometry 'omic studies.

Mass spectrometry is an important high-throughput technique for profiling small molecular compounds in biological samples and is widely used to identify potential diagnostic and prognostic compounds associated with disease. Commonly, this data generated by mass spectrometry has many missing values resulting when a compound is absent from a sample or is present but at a concentration below the detection limit. Several strategies are available for statistically analyzing data with missing values.

Chip-based nLC-TOF-MS is a highly stable technology for large-scale high-throughput analyses.

Many studies focused on the discovery of novel biomarkers for the diagnosis and treatment of disease states are facilitated by mass spectrometry-based technology. HPLC coupled to mass spectrometry is widely used; miniaturization of this technique using nano-liquid chromatography (LC)-mass spectrometry (MS) usually results in better sensitivity, but is associated with limited repeatability. The recent introduction of chip-based technology has significantly improved the stability of nano-LC-MS, but no substantial studies to verify this have been performed.

Isomer-specific chromatographic profiling yields highly sensitive and specific potential N-glycan biomarkers for epithelial ovarian cancer.

Aberrant glycosylation has been observed for decades in essentially all types of cancer, and is now well established as an indicator of carcinogenesis. Mining the glycome for biomarkers, however, requires analytical methods that can rapidly separate, identify, and quantify isomeric glycans. We have developed a rapid-throughput method for chromatographic glycan profiling using microfluidic chip-based nanoflow liquid chromatography (nano-LC)/mass spectrometry.

The glycolyzer: automated glycan annotation software for high performance mass spectrometry and its application to ovarian cancer glycan biomarker discovery.

Human serum glycomics is a promising method for finding cancer biomarkers but often lacks the tools for streamlined data analysis. The Glycolyzer software incorporates a suite of analytic tools capable of identifying informative glycan peaks out of raw mass spectrometry data. As a demonstration of its utility, the program was used to identify putative biomarkers for epithelial ovarian cancer from a human serum sample set.

Venous thromboembolism in uterine cancer.

Objectives: To determine the incidence, time course, and risk factors associated with the development of venous thromboembolism (VTE) and the effect of VTE on survival in women with uterine cancer.

Methods: Using the California Cancer Registry, the date, stage, and histology of all incident uterine cancer cases during 1993-1999 were identified. These cases were linked with the state's hospital discharge database, allowing identification of incident VTE events, after excluding cases with a previous history of VTE.

Surgical staging of early stage epithelial ovarian cancer: results from the CDC-NPCR ovarian patterns of care study.

Objectives: The objectives of this study were to determine the adequacy of surgical staging performed on surgically treated epithelial ovarian cancer (EOC) patients with apparent early stage disease and to determine if receipt of surgical staging had an influence on survival.

Methods: Detailed surgical staging information was collected from medical records for 721 patients diagnosed between 1998 and 2000 with EOC. Patients resided in California or New York and were identified through population-based cancer registries.

Human serum processing and analysis methods for rapid and reproducible N-glycan mass profiling.

Glycans constitute a new class of compounds for biomarker discovery. Glycosylation is a common post-translational modification and is often associated with transformation to malignancy. To analyze glycans, they are released from proteins, enriched, and measured with mass spectrometry.

Laparoscopic versus abdominal hysterectomy for endometrial cancer: comparison of patient outcomes.

Objective: To compare the demographics, cancer characteristics, and hospital outcomes of endometrial cancer patients undergoing a laparoscopically assisted vaginal hysterectomy (LAVH) versus a total abdominal hysterectomy (TAH).

Methods: Two California population databases (Office of Statewide Health Planning and Development and the California Cancer Registry) were linked using patient identifiers. Patients who underwent endometrial cancer surgery from 1997 to 2001 were identified.

The development of retrosynthetic glycan libraries to profile and classify the human serum N-linked glycome.

Annotation of the human serum N-linked glycome is a formidable challenge but is necessary for disease marker discovery. A new theoretical glycan library was constructed and proposed to provide all possible glycan compositions in serum. It was developed based on established glycobiology and retrosynthetic state-transition networks.

Detecting glycan cancer biomarkers in serum samples using MALDI FT-ICR mass spectrometry data.

Motivation: The development of better tests to detect cancer in its earliest stages is one of the most sought-after goals in medicine. Especially important are minimally invasive tests that require only blood or urine samples. By profiling oligosaccharides cleaved from glycosylated proteins shed by tumor cells into the blood stream, we hope to determine glycan profiles that will help identify cancer patients using a simple blood test.