A case series and review of stereotactic body radiation therapy for contiguous multilevel spine metastases.

Purpose: A majority of published series report on stereotactic body radiation therapy (SBRT) for 1-2 contiguous vertebral levels due to concerns regarding setup accuracy and radiation toxicity. This study evaluates patients with metastases spanning ≥ 3 contiguous levels treated with SBRT and augments its findings with a review of other studies investigating multilevel spine SBRT.

Methods: Analysis of a prospectively collected database of 49 patients with 55 metastases spanning ≥ 3 contiguous vertebral levels treated with SBRT at a single institution (2002-2023) was performed.

Matched three-dimensional organoids and two-dimensional cell lines of melanoma brain metastases mirror response to targeted molecular therapy.

Despite advances in the treatment paradigm for patients with metastatic melanoma, melanoma brain metastasis (MBM) continues to represent a significant treatment challenge. The study of MBM is limited, in part, by shortcomings in existing preclinical models. Surgically eXplanted Organoids (SXOs) are ex vivo, three-dimensional cultures prepared from primary tissue samples with minimal processing that recapitulate genotypic and phenotypic features of parent tumors without an artificial extracellular scaffold.

High-Throughput Empirical and Virtual Screening to Discover Novel Inhibitors of Polyploid Giant Cancer Cells in Breast Cancer.

Therapy resistance in breast cancer is increasingly attributed to polyploid giant cancer cells (PGCCs), which arise through whole-genome doubling and exhibit heightened resilience to standard treatments. Characterized by enlarged nuclei and increased DNA content, these cells tend to be dormant under therapeutic stress, driving disease relapse. Despite their critical role in resistance, strategies to effectively target PGCCs are limited, largely due to the lack of high-throughput methods for assessing their viability.

Stereotactic radiosurgery for patients with spinal metastases from prostate cancer.

Purpose: Spinal metastases may result in intractable pain, neurological deficit, and vertebral body collapse. There are only a few studies describing outcomes following spine stereotactic radiosurgery (SRS) specifically for prostate cancer metastases.

Methods: A prospectively collected database of patients with prostate cancer spinal metastases treated at the University of Pittsburgh Medical Center from 2003 to 2023 was analyzed.

Advances in Single-Cell Techniques for Linking Phenotypes to Genotypes.

Single-cell analysis has become an essential tool in modern biological research, providing unprecedented insights into cellular behavior and heterogeneity. By examining individual cells, this approach surpasses conventional population-based methods, revealing critical variations in cellular states, responses to environmental cues, and molecular signatures. In the context of cancer, with its diverse cell populations, single-cell analysis is critical for investigating tumor evolution, metastasis, and therapy resistance.

Body-Wide Inactivation of the Myc-Like Mlx Transcription Factor Network Accelerates Aging and Increases the Lifetime Cancer Incidence.

The "Mlx" and "Myc" transcription factor networks cross-communicate and share many common gene targets. Myc's activity depends upon its heterodimerization with Max, whereas the Mlx Network requires that the Max-like factor Mlx associate with the Myc-like factors MondoA or ChREBP. The current work demonstrates that body-wide Mlx inactivation, like that of Myc, accelerates numerous aging-related phenotypes pertaining to body habitus and metabolism.

Virtual multi-institutional tumor board: a strategy for personalized diagnoses and management of rare CNS tumors.

Purpose: Multidisciplinary tumor boards (MTBs) integrate clinical, molecular, and radiological information and facilitate coordination of neuro-oncology care. During the COVID-19 pandemic, our MTB transitioned to a virtual and multi-institutional format. We hypothesized that this expansion would allow expert review of challenging neuro-oncology cases and contribute to the care of patients with limited access to specialized centers.

Matched three-dimensional organoids and two-dimensional cell lines of melanoma brain metastases mirror response to targeted molecular therapy.

Purpose: Despite significant advances in the treatment paradigm for patients with metastatic melanoma, melanoma brain metastasis (MBM) continues to represent a significant treatment challenge. The study of MBM is limited, in part, by shortcomings in existing preclinical models. Surgically eXplanted Organoids (SXOs) are ex vivo, three-dimensional cultures prepared from primary tissue samples with minimal processing that recapitulate genotypic and phenotypic features of parent tumors and are grown without artificial extracellular scaffolding.

Single-cell morphological and transcriptome analysis unveil inhibitors of polyploid giant breast cancer cells in vitro.

Considerable evidence suggests that breast cancer therapeutic resistance and relapse can be driven by polyploid giant cancer cells (PGCCs). The number of PGCCs increases with the stages of disease and therapeutic stress. Given the importance of PGCCs, it remains challenging to eradicate them.

Microfluidic single-cell migration chip reveals insights into the impact of extracellular matrices on cell movement.

Cell migration is a complex process that plays a crucial role in normal physiology and pathologies such as cancer, autoimmune diseases, and mental disorders. Conventional cell migration assays face limitations in tracking a large number of individual migrating cells. To address this challenge, we have developed a high-throughput microfluidic cell migration chip, which seamlessly integrates robotic liquid handling and computer vision to swiftly monitor the movement of 3200 individual cells, providing unparalleled single-cell resolution for discerning distinct behaviors of the fast-moving cell population.

Results from a Real-World Multicenter Analysis of 482 Patients with Chronic Lymphocytic Leukemia Treated with Ibrutinib: A Look at Racial Differences.

Background: Despite recent approvals of lifesaving treatments for chronic lymphocytic leukemia (CLL), real-world data on the tolerability of the Bruton tyrosine kinase inhibitor ibrutinib for CLL treatment are lacking, especially in Black patients.

Objective: To expand upon a previously reported retrospective chart review of ibrutinib-treated patients with CLL to increase the number of sites and the enrollment period in first-line (1L) and relapsed/refractory (R/R) settings with a subanalysis based on ethnicity.

Patients And Methods: Adults with CLL who initiated ibrutinib treatment from five centers were followed for ≥ 6 months.

Human plasma-like medium facilitates metabolic tracing and enables upregulation of immune signaling pathways in glioblastoma explants.

Purpose: Metabolism within the tumor microenvironment (TME) represents an increasing area of interest to understand glioma initiation and progression. Stable isotope tracing is a technique critical to the study of tumor metabolism. Cell culture models of this disease are not routinely cultured under physiologically relevant nutrient conditions and do not retain cellular heterogeneity present in the parental TME.

High-Throughput Cellular Heterogeneity Analysis in Cell Migration at the Single-Cell Level.

Cancer cell migration represents an essential step toward metastasis and cancer deaths. However, conventional drug discovery focuses on cytotoxic and growth-inhibiting compounds rather than inhibitors of migration. Drug screening assays generally measure the average response of many cells, masking distinct cell populations that drive metastasis and resist treatments.

LANCE: a Label-Free Live Apoptotic and Necrotic Cell Explorer Using Convolutional Neural Network Image Analysis.

Identifying and quantifying cell death is the basis for all cell death research. Current methods for obtaining these quantitative measurements rely on established biomarkers, yet the marker-based approach suffers from limited marker specificity, high cost of reagents, lengthy sample preparation, and fluorescence imaging. Based on the morphological difference, we developed a Live, Apoptotic, and Necrotic Cell Explorer (LANCE) to categorize cell death status in a label-free manner, by incorporating machine learning and image processing.

Epidermal inclusion cyst in male breast: how to differentiate from other male breast lesions.

Male breast lesions are relatively less common. The most encountered malignant lesion in the male breast is ductal adenocarcinoma; and benign lesions are gynecomastia, fibrocystic disease, intramammary lymph node, fibroadenoma, lipoma and epidermal inclusion cyst (EIC), respectively [5,6]. To date, there had been published only a few cases of EIC of the male breast in literature [3,5,6].

Enfortumab vedotin in the treatment of urothelial cancers and beyond.

Enfortumab vedotin (EV) is the first antibody-drug conjugate approved for locally advanced or metastatic urothelial cancers (la/mUCs), a disease group historically associated with limited prognosis and therapeutic options. EV consists of monomethyl auristatin E, a microtubule-disrupting agent linked to an antibody targeting Nectin-4. In clinical trials, EV demonstrated high response rates and superior survival in the third-line setting for la/mUC compared with chemotherapy.

Chromosomal instability in adult-type diffuse gliomas.

Chromosomal instability (CIN) is a fundamental property of cancer and a key underlying mechanism of tumorigenesis and malignant progression, and has been documented in a wide variety of cancers, including colorectal carcinoma with mutations in genes such as APC. Recent reports have demonstrated that CIN, driven in part by mutations in genes maintaining overall genomic stability, is found in subsets of adult-type diffusely infiltrating gliomas of all histologic and molecular grades, with resulting elevated overall copy number burden, chromothripsis, and poor clinical outcome. Still, relatively few studies have examined the effect of this process, due in part to the difficulty of routinely measuring CIN clinically.

Global DNA methylation profiling reveals chromosomal instability in IDH-mutant astrocytomas.

Diffusely infiltrating gliomas are among the most common central nervous system tumors in adults. Over the past decade, the subcategorization of these tumors has changed to include both traditional histologic features and more recently identified molecular factors. However, one molecular feature that has yet to be integrated is the presence/absence of chromosomal instability (CIN).

Factors associated with symptom distress in women with breast cancer prior to initiation of chemotherapy.

Background: Symptom distress in women with breast cancer is associated with early discontinuation of chemotherapy and may influence treatment outcomes. Describing racial differences in prechemotherapy symptom distress and examining contextual variables of the symptom experience may inform our understanding of the complex problem of racial disparities in breast cancer.

Aim: To determine if perceived social support, healthcare system distrust, and economic hardship predict symptom distress in women with breast cancer prior to their first chemotherapy treatment.

Current strategies for intratumoural immunotherapy - Beyond immune checkpoint inhibition.

Immunotherapy has revolutionised cancer treatment through restoration of host antitumour immune response. Immune checkpoint inhibitors (ICIs) confer durable responses in only a subset of patients. Mechanisms of ICI resistance to improve durable response rates and overall survival are an area of intense clinical research.

Quantitation of Cabozantinib in Human Plasma by LC-MS/MS.

To support a phase III randomized trial of the multi-targeted tyrosine kinase inhibitor cabozantinib in neuroendocrine tumors, we developed a high-performance liquid chromatography mass spectrometry method to quantitate cabozantinib in 50 μL of human plasma. After acetonitrile protein precipitation, chromatographic separation was achieved with a Phenomenex synergy polar reverse phase (4 μm, 2 × 50 mm) column and a gradient of 0.1% formic acid in acetonitrile and 0.

Novel agents and regimens for hematological malignancies: recent updates from 2020 ASH annual meeting.

Antibodies and chimeric antigen receptor-engineered T cells (CAR-T) are increasingly used for cancer immunotherapy. Small molecule inhibitors targeting cellular oncoproteins and enzymes such as BCR-ABL, JAK2, Bruton tyrosine kinase, FLT3, BCL-2, IDH1, IDH2, are biomarker-driven chemotherapy-free agents approved for several major hematological malignancies. LOXO-305, asciminib, "off-the-shelf" universal CAR-T cells and BCMA-directed immunotherapeutics as well as data from clinical trials on many novel agents and regimens were updated at the 2020 American Society of Hematology (ASH) Annual Meeting.