Lemur tail kinase 3 serves as a predictor of patient outcomes and a target for the treatment of ovarian cancer.

Lemur tail kinase 3 (LMTK3) belongs to a family of tyrosine kinases that are known to correlate with tumor grade and patient survival in some cancers. Here, we validated LMTK3 as a specific target and a prognostic biomarker in ovarian cancer (OC). In samples from 204 stage I-II OC patients, immunohistochemical studies revealed a higher cytoplasmic-to-nuclear staining intensity of LMTK3, which correlated with worse overall survival ( < 0.

Utilizing machine learning to classify persistent organic pollutants in the serum of pregnant women: a predictive modeling approach.

Polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs), and per- and poly-fluoroalkyl substances (PFAS) are persistent organic pollutants (POPs) that remain detrimental to critical subpopulations, namely pregnant women. Required tests for biomonitoring are quite expensive. Moreover, statistical models aiming to discover the relationships between pollutants levels and human characteristics have their limitations.

Integrated transcriptomics- and structure-based drug repositioning identifies drugs with proteasome inhibitor properties.

Computational pharmacogenomics can potentially identify new indications for already approved drugs and pinpoint compounds with similar mechanism-of-action. Here, we used an integrated drug repositioning approach based on transcriptomics data and structure-based virtual screening to identify compounds with gene signatures similar to three known proteasome inhibitors (PIs; bortezomib, MG-132, and MLN-2238). In vitro validation of candidate compounds was then performed to assess proteasomal proteolytic activity, accumulation of ubiquitinated proteins, cell viability, and drug-induced expression in A375 melanoma and MCF7 breast cancer cells.

Multi-omics analysis identifies repurposing bortezomib in the treatment of kidney-, nervous system-, and hematological cancers.

Repurposing of FDA-approved drugs is a quick and cost-effective alternative to de novo drug development. Here, we identify genes involved in bortezomib sensitivity, predict cancer types that may benefit from treatment with bortezomib, and evaluate the mechanism-of-action of bortezomib in breast cancer (BT-474 and ZR-75-30), melanoma (A-375), and glioblastoma (A-172) cells in vitro. Cancer cell lines derived from cancers of the blood, kidney, nervous system, and skin were found to be significantly more sensitive to bortezomib than other organ systems.

Effects of Recombinant α-Microglobulin on Early Proteomic Response in Risk Organs after Exposure to Lu-Octreotate.

Recombinant α-microglobulin (A1M) is proposed as a protector during Lu-octreotate treatment of neuroendocrine tumors, which is currently limited by bone marrow and renal toxicity. Co-administration of Lu-octreotate and A1M could result in a more effective treatment by protecting healthy tissue, but the radioprotective action of A1M is not fully understood. The aim of this study was to examine the proteomic response of kidneys and bone marrow early after Lu-octreotate and/or A1M administration.

Digital RNA sequencing using unique molecular identifiers enables ultrasensitive RNA mutation analysis.

Mutation analysis is typically performed at the DNA level since most technical approaches are developed for DNA analysis. However, some applications, like transcriptional mutagenesis, RNA editing and gene expression analysis, require RNA analysis. Here, we combine reverse transcription and digital DNA sequencing to enable low error digital RNA sequencing.

Repurposing proteasome inhibitors for improved treatment of triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is associated with poor prognosis and limited treatment options due to the lack of important receptors (estrogen receptor [ER], progesterone receptor [PR], and human epidermal growth factor receptor 2 [HER2]) used for targeted therapy. However, high-throughput in vitro drug screening of cell lines is a powerful tool for identifying effective drugs for a disease. Here, we determine the intrinsic chemosensitivity of TNBC cell lines to proteasome inhibitors (PIs), thereby identifying potentially potent 2-drug combinations for TNBC.

Dioxins and furans maternal transfer: A study of breast milk and cord serum levels among Lebanese mothers and associations with newborn anthropometric measurements.

Dioxins and furans (PCDD/Fs) are anthropogenic pollutants that persist in the environment for long years, bioaccumulating in food & contaminating humans. In pregnancy, they can transfer through the placenta and reach the fetus, which negatively affects fetal growth. They can also reach newborns through breastfeeding.

Patient-derived scaffolds representing breast cancer microenvironments influence chemotherapy responses in adapted cancer cells consistent with clinical features.

Background: The tumor microenvironment clearly influences cancer progressing properties but less is known about how individual cancer microenvironments potentially moderate cancer treatment effects. By cultivating and treating cancer cell lines in patient-derived scaffolds (PDS), the impact of specific characteristics of individual cancer microenvironments can be incorporated in human-like growth modelling and cancer drug treatment testing.

Methods: PDSs from 78 biobanked primary breast cancer samples with known patient outcomes, were prepared and repopulated with donor breast cancer cell lines, followed by treatment with 5-fluorouracil or doxorubicin after cellular adaption to the various microenvironments.

Maternal Serum, Cord and Human Milk Levels of Per- and Polyfluoroalkyl Substances (PFAS), Association with Predictors and Effect on Newborn Anthropometry.

Background: The understanding of per- and polyfluoroalkyl substances (PFAS) health effects is rapidly advancing among critical populations. Therefore, the objective of this study was to assess PFAS serum levels among Lebanese pregnant women, cord serum and human milk levels, their determinants, and effects on newborn anthropometry.

Methods: We measured concentrations of six PFAS (PFHpA, PFOA, PFHxS, PFOS, PFNA and PFDA) using liquid chromatography MS/MS for 419 participants, of which 269 had sociodemographic, anthropometric, environmental and dietary information.

Co-administration with A1M does not influence apoptotic response of Lu-octreotate in GOT1 neuroendocrine tumors.

Recombinant α-microglobulin (A1M) is a proposed radioprotector during Lu-octreotate therapy of neuroendocrine tumors (NETs). To ensure a maintained therapeutic effect, we previously demonstrated that A1M does not affect the Lu-octreotate induced decrease in GOT1 tumor volume. However, the underlying biological events of these findings are still unknown.

Trefoil factor family proteins as potential diagnostic markers for mucinous invasive ovarian carcinoma.

Introduction: Ovarian cancer (OC) is the leading cause of gynecological cancer-related death. Of the main OC histologic subtypes, invasive mucinous carcinomas (MC) account for only 3% of OC cases and are frequently associated with favorable prognosis. Nevertheless, MCs differ greatly from the other OC histotypes in clinical, pathological, and biological behavior.

Pan-cancer analysis of genomic and transcriptomic data reveals the prognostic relevance of human proteasome genes in different cancer types.

Background: The human proteasome gene family (PSM) consists of 49 genes that play a crucial role in cancer proteostasis. However, little is known about the effect of PSM gene expression and genetic alterations on clinical outcome in different cancer forms.

Methods: Here, we performed a comprehensive pan-cancer analysis of genetic alterations in PSM genes and the subsequent prognostic value of PSM expression using data from The Cancer Genome Atlas (TCGA) containing over 10,000 samples representing up to 33 different cancer types.

Age and sex effects across the blood proteome after ionizing radiation exposure can bias biomarker screening and risk assessment.

Molecular biomarkers of ionizing radiation (IR) exposure are a promising new tool in various disciplines: they can give necessary information for adaptive treatment planning in cancer radiotherapy, enable risk projection for radiation-induced survivorship diseases, or facilitate triage and intervention in radiation hazard events. However, radiation biomarker discovery has not yet resolved the most basic features of personalized medicine: age and sex. To overcome this critical bias in biomarker identification, we quantitated age and sex effects and assessed their relevance in the radiation response across the blood proteome.

Pan-cancer analysis identifies BIRC5 as a prognostic biomarker.

Background: The BIRC5 gene encodes for the Survivin protein, which is a member of the inhibitor of apoptosis family. Survivin is found in humans during fetal development, but generally not in adult cells thereafter. Previous studies have shown that Survivin is abundant in most cancer cells, thereby making it a promising target for anti-cancer drugs and a potential prognostic tool.

Age-related long-term response in rat thyroid tissue and plasma after internal low dose exposure to I.

I is used clinically for therapy, and may be released during nuclear accidents. After the Chernobyl accident papillary thyroid carcinoma incidence increased in children, but not adults. The aims of this study were to compare I irradiation-dependent differences in RNA and protein expression in the thyroid and plasma of young and adult rats, and identify potential age-dependent biomarkers for I exposure.

Association between dietary quality indices and serum polychlorinated biphenyls and organochlorine pesticides levels among Lebanese adults.

Polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) remain a global concern in both developed and developing countries. Given that diet constitutes the major route of exposure to these pollutants, the objective of the current study is to investigate PCBs and OCPs serum levels in relation to dietary quality indices in a sample of Lebanese adults. Sociodemographic, nutritional, and anthropometric data were obtained from 302 participants in face-to-face interviews.

Correction: Long-term transcriptomic and proteomic effects in Sprague Dawley rat thyroid and plasma after internal low dose 131I exposure.

[This corrects the article DOI: 10.1371/journal.pone.

Prognostic Significance of BIRC5/Survivin in Breast Cancer: Results from Three Independent Cohorts.

Breast cancer (BC) histological and molecular classifications significantly improved the treatment strategy and prognosis. Inhibitor of apoptosis BIRC5/survivin is often overexpressed in cancers, however, indications of its importance in BC are inconsistent. We integrate BIRC5 protein and mRNA measures with clinical associates and long-term outcome in three independent cohorts Protein levels of BIRC5 were measured in primary lysates of 845 patients of the West Swedish BC cohort (VGR-BC) and linked to 5- and 27-years survival.

Genetic alterations associated with multiple primary malignancies.

Breast cancer (BC) patients are frequently at risk of developing other malignancies following treatment. Although studies have been conducted to elucidate the etiology of multiple primary malignancies (MPM) after a BC diagnosis, few studies have investigated other previously diagnosed primary malignancies (OPPM) before BC. Here, genome-wide profiling was used to identify potential driver DNA copy number alterations and somatic mutations that promote the development of MPMs.

Long-term transcriptomic and proteomic effects in Sprague Dawley rat thyroid and plasma after internal low dose 131I exposure.

Background: Radioiodide (131I) is commonly used to treat thyroid cancer and hyperthyroidis.131I released during nuclear accidents, have resulted in increased incidence of thyroid cancer in children. Therefore, a better understanding of underlying cellular mechanisms behind 131I exposure is of great clinical and radiation protection interest.

Maternal and cord serum levels of polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) among Lebanese pregnant women and predictors of exposure.

In this study, the six indicator non-dioxin-like polychlorinated biphenyls NDL-PCBs (PCB28, PCB52, PCB101, PCB138, PCB153, PCB180), as well as four organochlorine pesticides (OCPs), hexachlorobenzene (HCB), β-hexachlorocyclohexane (β-HCH), dichlorodiphenyltrichloroethane (DDT), and dichlorodiphenyldichlorethylene (DDE) were measured in 98 maternal and 49 cord sera samples of a group of Lebanese women who gave birth in three hospitals in Greater Beirut, between March and July 2018. Results showed that the levels of these persistent organic pollutants (POPs) in maternal serum were below critical limits as well as those in other countries (Tunisia, France, Portugal, Spain, Poland, Greenland, Canada, Brazil, and China). The ratios of cord serum concentrations to maternal serum concentrations of analyzed POPs were higher than 1.

Male Breast Carcinoma after Irradiation and Long-Term Phenothiazine Exposure: A Case Report.

We present a young male patient with breast cancer having several risk factors likely acting in consort: irradiation of the breast for gynecomastia in adolescence and a life-long administration of phenothiazine for schizophrenia from the age of 16 years, with elevated serum prolactin level resulting in breast cancer development 24 years after irradiation.

Previously diagnosed multiple primary malignancies in patients with breast carcinoma in Western Sweden between 2007 and 2018.

Purpose: Multiple primary malignancies (MPMs) caused by breast cancer treatment are well described, but only few studies to date describe which other previous primary malignancies (OPPMs) occur before breast cancer. The purpose of the present study was to evaluate the prevalence of OPPMs in patients with breast cancer between 2007 and 2018 in Western Sweden.

Methods: Patient selection was performed using both pathology reports at Sahlgrenska University Hospital (Sweden) and the Swedish Cancer Registry.