Mechanical Disruption by Focused Ultrasound Re-sensitizes ER+ Breast Cancer Cells to Hormone Therapy.

Objective: Tamoxifen is the most used agent to treat estrogen receptor-positive (ER+) breast cancer (BC). While it decreases the risk of cancer recurrence by 50%, many patients develop resistance to this treatment, culminating in highly aggressive disease. Tamoxifen resistance comes from the repression of ER transcriptional activity that switches the cancer cells to proliferation via nonhormonal signaling pathways.

A case of cetuximab-induced radiation recall skin dermatitis and review of the literature.

Radiation recall presents as an acute inflammatory reaction triggered by systemic therapy, usually chemotherapy, and is typically limited to an area that was previously irradiated. Radiation recall reactions are generally self-limiting and most commonly occur in the skin. Many systemic agents have been described to elicit a radiation recall reaction, but the exact pathogenesis is largely unknown.

Correction: Evaluation of deacetylase inhibition in metaplastic breast carcinoma using multiple derivations of preclinical models of a new patient-derived tumor.

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

Family history and pathogenic/likely pathogenic germline variants in prostate cancer patients.

Background: Recent literature highlights the importance of germline genetic testing in prostate cancer (PCa) patients. Surprisingly, a literature review indicates that family history (FH) records are incomplete in the major published studies from prostate cancer patients.

Methods: Prospective family history data were gathered from 496 men in a single institution with a personal history of PCa who underwent germline genetic testing using a panel of at least 79 genes.

Evaluation of deacetylase inhibition in metaplastic breast carcinoma using multiple derivations of preclinical models of a new patient-derived tumor.

Metaplastic breast carcinoma (MBC) is a clinically aggressive and rare subtype of breast cancer, with similar features to basal-like breast cancers. Due to rapid growth rates and characteristic heterogeneity, MBC is often unresponsive to standard chemotherapies; and novel targeted therapeutic discovery is urgently needed. Histone deacetylase inhibitors (DACi) suppress tumor growth and metastasis through regulation of the epithelial-to-mesenchymal transition axis in various cancers, including basal-like breast cancers.

Image-Guided Intensity-Modulated Radiation Therapy for IgG4-Related Ophthalmic Disease.

Background: IgG4-related ophthalmic disease is a rare, newly recognized entity with high failure rates on first-line therapy of systemic corticosteroids and no other proven management options. Here, we present the clinical course of a patient with IgG4 ophthalmic disease who achieved a favorable response from radiotherapy. Our patient initially presented with a history of recurrent painful flares of orbital inflammation, a pathologic diagnosis follicular lymphoid hyperplasia from a right lacrimal gland biopsy, and MRI imaging noting expansion of the lateral rectus muscle of the right eye.

A novel screening approach comparing kinase activity of small molecule inhibitors with similar molecular structures and distinct biologic effects in triple-negative breast cancer to identify targetable signaling pathways.

Breast cancer affects women globally; the majority of breast cancer-related mortalities are due to metastasis. Acquisition of a mesenchymal phenotype has been implicated in the progression of breast cancer cells to an invasive, metastatic state. Triple-negative breast cancer (TNBC) subtypes have high rates of metastases, recurrence, and have poorer prognoses compared to other breast cancer types, partially due to lack of commonly targeted receptors.

Obesity-Altered Adipose Stem Cells Promote Radiation Resistance of Estrogen Receptor Positive Breast Cancer through Paracrine Signaling.

Obesity is associated with poorer responses to chemo- and radiation therapy for breast cancer, which leads to higher mortality rates for obese women who develop breast cancer. Adipose stem cells (ASCs) are an integral stromal component of the tumor microenvironment (TME). In this study, the effects of obesity-altered ASCs (obASCs) on estrogen receptor positive breast cancer cell's (ERBCCs) response to radiotherapy (RT) were evaluated.

Acellular Biologic Nipple-Areolar Complex Graft: Murine and Nonhuman Primate Host Response Evaluation.

There are more than 3 million breast cancer survivors living in the United States of which a significant number have undergone mastectomy followed by breast and nipple-areolar complex (NAC) reconstruction. Current strategies for NAC reconstruction are dependent on nonliving or nonpermanent techniques, including tattooing, nipple prosthetics, or surgical nipple-like structures. Described herein is a tissue engineering approach demonstrating the feasibility of an allogeneic acellular graft for nipple reconstruction.

Leptin produced by obesity-altered adipose stem cells promotes metastasis but not tumorigenesis of triple-negative breast cancer in orthotopic xenograft and patient-derived xenograft models.

Background: Breast cancer is the second leading cause of cancer deaths in the USA. Triple-negative breast cancer (TNBC) is a clinically aggressive subtype of breast cancer with high rates of metastasis, tumor recurrence, and resistance to therapeutics. Obesity, defined by a high body mass index (BMI), is an established risk factor for breast cancer.

TrxR1, Gsr, and oxidative stress determine hepatocellular carcinoma malignancy.

Thioredoxin reductase-1 (TrxR1)-, glutathione reductase (Gsr)-, and Nrf2 transcription factor-driven antioxidant systems form an integrated network that combats potentially carcinogenic oxidative damage yet also protects cancer cells from oxidative death. Here we show that although unchallenged wild-type (WT), TrxR1-null, or Gsr-null mouse livers exhibited similarly low DNA damage indices, these were 100-fold higher in unchallenged TrxR1/Gsr-double-null livers. Notwithstanding, spontaneous cancer rates remained surprisingly low in TrxR1/Gsr-null livers.

Obesity-Altered Adipose Stem Cells Promote ER⁺ Breast Cancer Metastasis through Estrogen Independent Pathways.

Adipose stem cells (ASCs) play an essential role in tumor microenvironments. These cells are altered by obesity (obASCs) and previous studies have shown that obASCs secrete higher levels of leptin. Increased leptin, which upregulates estrogen receptor alpha (ERα) and aromatase, enhances estrogen bioavailability and signaling in estrogen receptor positive (ER⁺) breast cancer (BC) tumor growth and metastasis.

Drug resistance profiling of a new triple negative breast cancer patient-derived xenograft model.

Background: Triple-negative breast cancer (TNBC) represents an aggressive subtype with limited therapeutic options. Experimental preclinical models that recapitulate their tumors of origin can accelerate target identification, thereby potentially improving therapeutic efficacy. Patient-derived xenografts (PDXs), due to their genomic and transcriptomic fidelity to the tumors from which they are derived, are poised to improve the preclinical testing of drug-target combinations in translational models.

Therapeutic Potential of Adipose Stem Cells.

Adipose stem cells (ASCs) have gained attention in the fields of stem cells regenerative medicine due to their multifaceted therapeutic capabilities. Promising preclinical evidence of ASCs has supported the substantial interest in the use of these cells as therapy for human disease. ASCs are an adult stem cell resident in adipose tissue with the potential to differentiation along mesenchymal lineages.

Panobinostat suppresses the mesenchymal phenotype in a novel claudin-low triple negative patient-derived breast cancer model.

Claudin-low triple negative breast cancer (CL-TNBC) is a clinically aggressive molecular TNBC subtype characterized by a propensity to metastasize, recur and acquire chemoresistance. CL-TNBC has a diverse intra- and extracellular composition and microenvironment, and currently there are no clinically approved targeted therapies. Histone deacetylase inhibitors (HDACi) have been investigated as therapeutic agents targeting invasive TNBC phenotypes.

A novel patient-derived xenograft model for claudin-low triple-negative breast cancer.

Background: Triple-negative breast cancer (TNBC) subtypes are clinically aggressive and cannot be treated with targeted therapeutics commonly used in other breast cancer subtypes. The claudin-low (CL) molecular subtype of TNBC has high rates of metastases, chemoresistance and recurrence. There exists an urgent need to identify novel therapeutic targets in TNBC; however, existing models utilized in target discovery research are limited.

Melanoma complicating treatment with natalizumab for multiple sclerosis: A report from the Southern Network on Adverse Reactions (SONAR).

A 43-year-old female with multiple sclerosis developed urethral melanoma. The only potential risk factor was treatment with natalizumab, a humanized monoclonal antibody against α4 integrins. To investigate the risk-exposure relationship, we reviewed this case, all other published cases, and cases of natalizumab-associated melanoma reported to regulatory agencies.