Effective Radiation Therapy for Isolated Apical Pulmonary Amyloidoma: A Case Report and Treatment Insight.

BACKGROUND Amyloidosis refers to an assortment of diseases characterized by the accumulation and deposition of misfolded proteins in the extracellular matrix of tissues and organs. It may present systemically, affecting multiple organs, or locally by affecting a single organ. When the lungs or mediastinal structures are involved, the term pulmonary amyloid is used. Sole pulmonary involvement with amyloid is extremely rare. There is no definitive treatment for this disease, but proposed treatment options include surgery, cytotoxic medications, and external beam radiation therapy (EBRT). CASE REPORT A 68-year-old man with a left apical lung mass presented with subacute shortness of breath. Comprehensive evaluation of the patient's symptoms and findings, including infectious and oncologic evaluation, were performed. Infectious evaluation revealed positive acid-fast bacilli sputum cultures with Mycobacterium chimerea intracellulare. Biopsy of the mass revealed a Lambda restricted amyloidoma, which is usually seen in lymphoproliferative diseases and disorders. Bone marrow biopsy did not reveal any monoclonal cell lines or neoplasms. Abdominal fat pad biopsy was performed to rule out systemic amyloid and the results were negative. The diagnosis of isolated apical pulmonary amyloidoma was made. EBRT was performed over 12 fractions in 24 mGy, with improvement in the patient's symptoms. CONCLUSIONS The diagnosis of pulmonary amyloid necessitates comprehensive evaluation. There is no specific treatment for pulmonary amyloid; however, there has been success with surgical intervention, cytotoxic medications, and EBRT. Successful treatment of the amyloidoma is based on its anatomic location. We suggest EBRT in fractionated doses for optimal treatment of rare isolated apical pulmonary amyloidoma.

Androgen Receptor Signaling in Castration-Resistant Prostate Cancer Alters Hyperpolarized Pyruvate to Lactate Conversion and Lactate Levels In Vivo.

PURPOSE: Androgen receptor (AR) signaling affects prostate cancer (PCa) growth, metabolism, and progression. Often, PCa progresses from androgen-sensitive to castration-resistant prostate cancer (CRPC) following androgen-deprivation therapy. Clinicopathologic and genomic characterizations of CRPC tumors lead to subdividing CRPC into two subtypes: (1) AR-dependent CRPC containing dysregulation of AR signaling alterations in AR such as amplification, point mutations, and/or generation of splice variants in the AR gene; and (2) an aggressive variant PCa (AVPC) subtype that is phenotypically similar to small cell prostate cancer and is defined by chemotherapy sensitivity, gain of neuroendocrine or pro-neural marker expression, loss of AR expression, and combined alterations of PTEN, TP53, and RB1 tumor suppressors. Previously, we reported patient-derived xenograft (PDX) animal models that contain characteristics of these CRPC subtypes. In this study, we have employed the PDX models to test metabolic alterations in the CRPC subtypes. PROCEDURES: Mass spectrometry and nuclear magnetic resonance analysis along with in vivo hyperpolarized 1-[13C]pyruvate spectroscopy experiments were performed on prostate PDX animal models. RESULTS: Using hyperpolarized 1-[13C]pyruvate conversion to 1-[13C]lactate in vivo as well as lactate measurements ex vivo, we have found increased lactate production in AR-dependent CRPC PDX models even under low-hormone levels (castrated mouse) compared to AR-negative AVPC PDX models. CONCLUSIONS: Our analysis underscores the potential of hyperpolarized metabolic imaging in determining the underlying biology and in vivo phenotyping of CRPC.

Metabolic Differences in Glutamine Utilization Lead to Metabolic Vulnerabilities in Prostate Cancer.

The new oncologic paradigm of precision medicine is focused on identifying metabolic, proteomic, transcriptomic and genomic variabilities in tumors that can be exploited to tailor treatments and improve patient outcomes. Metabolic changes are a hallmark of cancer, and inhibition of metabolic pathways is now a major strategy in medicinal chemistry for targeting cancers. However, non-invasive biomarkers to categorize metabolic subtypes are in short supply. The purpose of this study was to characterize the intracellular and extracellular metabolic profiles of four prostate cancer cell lines with varying degrees of aggressiveness. We observed metabolic differences between the aggressive prostate cancer cell line PC3 and the even more aggressive, metastatic subline PC3M assessed by hyperpolarized in vivo pyruvate studies, nuclear magnetic resonance spectroscopy, and carbon-13 feeding studies. On further examination of the differences between these two cell lines, we found increased glutamine utilization in the metastatic PC3M subline that led directly to sensitivity to glutaminase inhibitor CB-839. Our study supports the theory that metastatic progression increases glutamine utilization and the inhibition of glutaminolysis could have clinical implications.