Mutability and hypermutation antagonize immunoglobulin codon optimality.

The efficacy of antibody responses is inherently linked to paratope diversity, as generated through V(D)J recombination and somatic hypermutation. Despite this, it is unclear how genetic diversification mechanisms evolved alongside codon optimality and affect antibody expression. Here, we analyze germline immunoglobulin (IG) genes, natural V(D)J repertoires, serum IgG, and monoclonal antibody (mAb) expression through the lens of codon optimality.

Site of vulnerability on SARS-CoV-2 spike induces broadly protective antibody against antigenically distinct Omicron subvariants.

The rapid evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants has emphasized the need to identify antibodies with broad neutralizing capabilities to inform future monoclonal therapies and vaccination strategies. Herein, we identified S728-1157, a broadly neutralizing antibody (bnAb) targeting the receptor-binding site (RBS) that was derived from an individual previously infected with WT SARS-CoV-2 prior to the spread of variants of concern (VOCs). S728-1157 demonstrated broad cross-neutralization of all dominant variants, including D614G, Beta, Delta, Kappa, Mu, and Omicron (BA.

Localized opacification of hydrophilic acrylic intraocular lenses after procedures using intracameral injection of air or gas.

Purpose: To describe clinical and laboratory findings in a series of cases of intraocular lens (IOL) opacification after procedures involving intracameral injections of air or gas.

Setting: John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA.

Urinary angiostatin levels are elevated in patients with epithelial ovarian cancer.

Objective: The poor prognosis associated with epithelial ovarian cancer (EOC) is due to the lack of overt early symptoms and the absence of reliable diagnostic screening methods. Since many tumors over express angiogenic regulators, the purpose of this study was to determine whether elevated levels of the angiogenic or angiostatic molecules vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), endostatin (ES), and angiostatin (AS) were elevated in plasma and urine from patients with EOC.

Methods: VEGF, HGF, ES and AS were assayed by ELISA in samples from pilot cohort consisting of healthy women (N=48; pre-menopausal N=23, post-menopausal N=25), women with benign gynecological disease (N=54), patients with primary peritoneal cancer (PP) (N=2) and EOC (N=35).

Human ovarian surface epithelial cells immortalized with hTERT maintain functional pRb and p53 expression.

Objective: Cell immortalization is considered to be a prerequisite status for carcinogenesis. Normal human ovarian surface epithelial (OSE) cells, which are thought to be the origin of most of human ovarian carcinomas, have a very limited lifespan in culture. Establishment of immortalized OSE cell lines has, in the past, required inactivation of pRb and p53 functions.

Aberrant regulation of argininosuccinate synthetase by TNF-alpha in human epithelial ovarian cancer.

The pro-inflammatory cytokine, tumour necrosis factor-alpha, TNF-alpha, is dysregulated in malignant compared with normal ovarian surface epithelium (OSE). Several epidemiological studies have associated inflammation with ovarian tumorigenesis, with TNF-alpha playing a key role in modulating invasion, angiogenesis and metastasis. Here, we show that TNF-alpha also induces expression of arate-limiting enzyme in arginine synthesis, argininosuccinate synthetase (AS), thereby linking inflammation with several arginine-dependent metabolic pathways, implicated in accelerated carcinogenesis and tumour progression.

Expression and regulation of tumor necrosis factor alpha in normal and malignant ovarian epithelium.

Epidemiologic studies implicate inflammatory stimuli in the development of ovarian cancer. The proinflammatory cytokine tumor necrosis factor alpha (TNF-alpha) and both its receptors (TNFRI and TNFRII) are expressed in biopsies of this malignancy. Here, we tested the hypothesis that TNF-alpha is a regulator of the proinflammatory microenvironment of ovarian cancer.

BRCA1 and BRCA2 mutations account for a large proportion of ovarian carcinoma cases.

Background: It is believed that BRCA1 and BRCA2 germline mutations account for the majority of hereditary ovarian carcinomas; however, to the authors' knowledge, there are scant data on the prevalence and spectrum of mutations, genotype/phenotype correlations, tumor histology, and family history characteristics. To address this gap, the authors conducted a population-based study of 232 incident epithelial ovarian carcinomas in the Tampa Bay area.

Methods: Genetic testing for the BRCA1 and BRCA2 genes was performed through full sequencing and BRCA1 rearrangement testing.

Lysophospholipids are potential biomarkers of ovarian cancer.

Objective: To determine whether lysophosphatidic acid (LPA) and other lysophospholipids (LPL) are useful markers for diagnosis and/or prognosis of ovarian cancer in a controlled setting.

Method: Plasma samples were collected from ovarian cancer patients and healthy control women in Hillsborough and Pinellas counties, Florida, and processed at the University of South Florida H. Lee Moffitt Cancer Center and Research Institute (Moffitt).

A modified medium that significantly improves the growth of human normal ovarian surface epithelial (OSE) cells in vitro.

Approximately 90% of malignant ovarian tumours are epithelial and thought to arise from a single cell layer, the ovarian surface epithelium. In culture, human normal ovarian surface epithelial (OSE) cells have a very limited lifespan before they senesce, rarely progressing beyond 10 population doublings. This has restricted the use of normal OSE cells for studying the biology of ovarian surface epithelium and identifying molecular events that contribute to malignant transformation.

Insulin-like growth factors, insulin-like growth factor-binding proteins, and endometrial cancer in postmenopausal women: results from a U.S. case-control study.

Objective: To assess whether circulating insulin-like growth factor-1 (IGF-1), IGF-2, insulin-like growth factor-binding protein-1 (IGFBP-1), or IGFBP-3 were associated with endometrial cancer in postmenopausal women.

Study Design: Between 1987 and 1990, we conducted a case-control study of 405 women with endometrial cancer and 297 matched population-based controls. This analysis included 174 postmenopausal cases and 136 controls.

Cytology of human ovarian surface epithelial brushings.

Background: The human ovarian surface epithelium (HOSE) is the putative source of ovarian epithelial cancer, the most lethal gynecologic malignancy that affects women in the United States. The current study was designed to provide a database of normal HOSE cell features for diagnostic and research applications.

Methods: HOSE was harvested from 42 women undergoing laparoscopy or laparotomy for benign gynecologic disorders, infertility problems, or pregnancy.

Molecular assessment of depth of myometrial invasion in stage I endometrial cancer: a model based on K-ras mutation analysis.

Introduction: Overall nearly 20% of endometrial cancer (EC) patients die of the disease and over half of these had initially presented with clinical stage I disease. There is a strong correlation between disease mortality and depth of myometrial invasion. Current assessment of depth of invasion relies on light microscopy.

Detection of tumour lymphovascular space invasion using dual cytokeratin and CD31 immunohistochemistry.

Background: Lymphovascular space invasion (LVSI) is an important step in the complex process of tumour metastasis. Various methods have been used in the past to improve the histological detection of LVSI.

Aims: To develop a sensitive immunohistochemical method for the detection of LVSI.

Multiple actions of the chemokine CXCL12 on epithelial tumor cells in human ovarian cancer.

Of 14 chemokine receptors investigated, only CXCR4 was expressed on ovarian cancer cells [C. J. Scotton et al.

Insights from gene arrays on the development and growth regulation of uterine leiomyomata.

Objective: To use microarray analysis as an unbiased approach to identify genes involved in the induction and growth of uterine leiomyomata.

Design: Screen by arrays for up to 12,000 genes in leiomyoma (L) and control myometrium (M) from nine patients.

Setting: University research laboratories.

Tumor cytotoxicity of peritoneal macrophages and peripheral blood monocytes from patients with ovarian, endometrial, and cervical cancer.

The purpose of this study was to compare the cytotoxic capacity of peritoneal macrophages (PM) and peripheral blood monocytes (PBM) from patients with ovarian, endometrial, and cervical cancers after in vitro activation with gamma interferon (IFN-gamma) and lipopolysaccharide (LPS). Peritoneal macrophages were obtained from ascites or peritoneal washings and peripheral blood monocytes via peripheral venipuncture from 58 patients: 17 with ovarian, 19 with endometrial, and 10 with cervical cancers. PBM and PM from 12 patients with nonmalignant gynecologic conditions served as controls.

Tubal sterilization and risk of cancer of the endometrium.

Objective: Surgical sterilization is a common method of contraception among U.S. women.

IL-2 enhances standard IFNgamma/LPS activation of macrophage cytotoxicity to human ovarian carcinoma in vitro: a potential for adoptive cellular immunotherapy.

Objective: The objective was to evaluate the enhancement of human peritoneal macrophage cytotoxic in vitro activity by the addition of interleukin-2 (IL-2) to the standard interferon gama (IFNgamma) and lipopolysaccharide (LPS) activation procedure used for cellular adoptive immunotherapy in a human ovarian cancer system. This cytotoxic effect of these activated macrophages was tested on cells from ovarian cancers of various stages, histology type, and grade, both prior to chemotherapy and at recurrence, in ovarian carcinoma cells lines and normal cells. Increased activation of the macrophage may make it a better candidate for intraperitoneal cellular adoptive immunotherapy as a component of ovarian cancer therapy.

Evidence for a common etiology for endometrial carcinomas and malignant mixed mullerian tumors.

Objective: To elucidate factors linked to the development of malignant mixed mullerian tumors (MMMT) and determine whether the risk factor profile for these tumors corresponds with that for the more common endometrial carcinomas.

Methods: A multicenter case-control study of 424 women diagnosed with endometrial carcinoma, 29 women diagnosed with MMMT, and 320 community controls was conducted. Review of pathological reports and slides was performed to classify cases by histological type.

Analysis of histopathological features of endometrioid uterine carcinomas and epidemiologic risk factors.

A large case-control study was performed to determine whether risk factors for endometrioid carcinoma, the most common type of endometrial cancer, vary according to the histological features of the tumor. Study subjects consisted of 328 women with newly diagnosed endometrioid adenocarcinoma and 320 population-based control subjects. Variables studied included age at menarche, menopausal estrogen use, weight, parity, cigarette smoking, and oral contraceptive use.