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Journal of Biomedical Optics Jun 2024Hematogenous metastasis is mediated by circulating tumor cells (CTCs) and CTC clusters (CTCCs). We recently developed "diffuse flow cytometry" (DiFC) to detect...
SIGNIFICANCE
Hematogenous metastasis is mediated by circulating tumor cells (CTCs) and CTC clusters (CTCCs). We recently developed "diffuse flow cytometry" (DiFC) to detect fluorescent protein (FP) expressing CTCs in small animals. Extending DiFC to allow detection of two FPs simultaneously would allow concurrent study of different CTC sub-populations or heterogeneous CTCCs in the same animal.
AIM
The goal of this work was to develop and validate a two-color DiFC system capable of non-invasively detecting circulating cells expressing two distinct FPs.
APPROACH
A DiFC instrument was designed and built to detect cells expressing either green FP (GFP) or tdTomato. We tested the instrument in tissue-mimicking flow phantoms and in multiple myeloma bearing mice .
RESULTS
In phantoms, we could accurately differentiate GFP+ and tdTomato+ CTCs and CTCCs. In tumor-bearing mice, CTC numbers expressing both FPs increased during disease. Most CTCCs (86.5%) expressed single FPs with the remainder both FPs. These data were supported by whole-body hyperspectral fluorescence cryo-imaging of the mice.
CONCLUSIONS
We showed that two-color DiFC can detect two populations of CTCs and CTCCs concurrently. This instrument could allow study of tumor development and response to therapies for different sub-populations in the same animal.
Topics: Animals; Mice; Neoplastic Cells, Circulating; Flow Cytometry; Phantoms, Imaging; Cell Line, Tumor; Humans; Multiple Myeloma; Equipment Design; Green Fluorescent Proteins
PubMed: 38818515
DOI: 10.1117/1.JBO.29.6.065003 -
Journal of Medicine and Life Feb 2024Systemic lupus erythematosus (SLE) affects multiple organ systems, and there has recently been increasing evidence that suggests a considerable rise in cancer risk.... (Review)
Review
Systemic lupus erythematosus (SLE) affects multiple organ systems, and there has recently been increasing evidence that suggests a considerable rise in cancer risk. Despite growing evidence, the relationship between SLE and multiple myeloma (MM) remains underlooked. This review synthesizes findings from case reports published between 2012 and 2023 to explore this relationship. We conducted a comprehensive search using PubMed, Embase, and Google Scholar with the keywords 'SLE' and 'multiple myeloma' and described the clinical profile of MM in patients with SLE. Seven case reports were reviewed. Five case reports included female participants, two had a simultaneous diagnosis of SLE and MM, and in others, MM followed SLE varying from 7 months to 30 years. Two cases reported an improvement in MM. Four cases reported death due to complications, which included shock, myocardial infarction, and pneumonia. Lupus nephritis was seen to complicate MM and SLE complex in 2 cases. Larger, well-developed studies focusing on clinical presentation, diagnostic strategy, treatment, and outcomes are needed to better understand the association between SLE and MM. Healthcare workers should be aware of the increased risk of malignancy in SLE and customize screening accordingly.
Topics: Adult; Female; Humans; Male; Middle Aged; Case Reports as Topic; Lupus Erythematosus, Systemic; Multiple Myeloma; Aged
PubMed: 38813361
DOI: 10.25122/jml-2023-0314 -
Journal of Medicine and Life Feb 2024Rosai-Dorfman disease (RDD) is a rare non-Langerhans cell histiocytosis disorder characterized by the proliferation of histiocytes within the lymph nodes. Extranodal...
Rosai-Dorfman disease (RDD) is a rare non-Langerhans cell histiocytosis disorder characterized by the proliferation of histiocytes within the lymph nodes. Extranodal involvement can occur; however, only 10% of extranodal RDD involve the skin. We present a unique case of a 66-year-old woman with cutaneous RDD followed by the development of multiple myeloma (MM). To our knowledge, this is only the second reported case where RDD preceded a diagnosis of MM, with the first documented instance occurring in 2018. The patient presented to the dermatology clinic with a 5-year history of painless, solitary lesion over the right cheek. Local examination revealed a single 6 mm x 7 mm well-circumscribed pearly telangiectatic lesion resembling basal cell carcinoma over the right nasolabial fold and cheek. The lesion was excised with a 3 mm circumferential margin. Histopathology showed a mixed lymphohistiocytic cell infiltrate with emperipolesis and immunohistochemical staining patterns consistent with RDD. Two years later, the patient presented with hip pain and was diagnosed with MM. She was treated with lenalidomide, bortezomib, and dexamethasone, and was later maintained on lenalidomide. Our case adds to the limited evidence suggesting a potential association between RDD and MM. Further research in this field is required to promptly identify and manage patients with such a presentation in the future.
Topics: Humans; Histiocytosis, Sinus; Female; Aged; Multiple Myeloma; Carcinoma, Basal Cell; Diagnosis, Differential; Skin Neoplasms; Face
PubMed: 38813357
DOI: 10.25122/jml-2023-0337 -
Oncoimmunology 2024Recently, it was revealed that the high-risk, poor-prognosis downregulation of GABA type A receptor-associated protein (GABARAP) causes a defect in both autophagy and...
Recently, it was revealed that the high-risk, poor-prognosis downregulation of GABA type A receptor-associated protein (GABARAP) causes a defect in both autophagy and surface exposure of calreticulin (CALR) in multiple myeloma (MM) cells responding to bortezomib. Hence, GABARAP-defective MM cells fail to undergo immunogenic cell death.
Topics: Multiple Myeloma; Humans; Bortezomib; Adaptor Proteins, Signal Transducing; Antineoplastic Agents; Microtubule-Associated Proteins; Apoptosis Regulatory Proteins; Immunogenic Cell Death; Cell Line, Tumor; Autophagy; Calreticulin
PubMed: 38812570
DOI: 10.1080/2162402X.2024.2360275 -
Blood Cancer Journal May 2024We evaluated the efficacy and safety of 24 cycles of Dara in combination with carfilzomib (K), lenalidomide (R), and dexamethasone (d) without autologous stem cell...
We evaluated the efficacy and safety of 24 cycles of Dara in combination with carfilzomib (K), lenalidomide (R), and dexamethasone (d) without autologous stem cell transplant (ASCT) in newly diagnosed multiple myeloma (NDMM) irrespective of ASCT eligibility in a single-arm, phase II study. The primary endpoint was the rate of stringent complete response (sCR) and/or measurable residual disease (MRD) < 10 by next-generation sequencing (NGS) at the end of cycle 8 (C8). MRD was also assessed on peripheral blood samples using both the EXENT system and liquid chromatography-mass spectrometry (LC-MS). Forty-two patients entered the treatment phase; forty were evaluable for the primary endpoint. The rate of sCR and/or MRD < 10 following C8 was 30/40 (75%), meeting the statistical threshold for efficacy. The 10 MRD negative rate improved with treatment beyond C8. Agreement between EXENT and NGS was high and increased over time; agreement between LC-MS and NGS was lower. The estimated 3-year progression-free survival progression-free survival was 85%, and 3-year overall survival was 95%. Upper respiratory infections occurred in 67% (7% grade 3-4). There were no treatment-related deaths. Extended frontline Dara-KRd induced a high rate of sCR and/or MRD negativity; the rate and depth of MRD negativity improved beyond C8.
Topics: Humans; Multiple Myeloma; Dexamethasone; Lenalidomide; Female; Male; Middle Aged; Aged; Antineoplastic Combined Chemotherapy Protocols; Oligopeptides; Antibodies, Monoclonal; Adult; Neoplasm, Residual; Treatment Outcome
PubMed: 38811560
DOI: 10.1038/s41408-024-01045-3 -
Asian Pacific Journal of Cancer... May 2024Multiple myeloma (MM) is the second most prevalent blood cancer after non-Hodgkin lymphoma. It is identified by the excessive production of abnormal monoclonal...
BACKGROUND
Multiple myeloma (MM) is the second most prevalent blood cancer after non-Hodgkin lymphoma. It is identified by the excessive production of abnormal monoclonal immunoglobulins, which can result in various clinical symptoms such as destructive bone lesions, renal dysfunction, anemia, and immunodeficiency. The current study aims to evaluate the serum levels of carboxy-terminal collagen crosslinks 1 (CTX-1), Fibulin-1, vitamin D3, LDH, and albumin in MM patients and their significance for early diagnosis.
MATERIALS AND METHODS
This study included 30 healthy controls (11 males, 19 females) and 60 patients with multiple myeloma (37 males and 23 females), aged between 40-60 years. Five-milliliter blood samples were collected and stored at -20°C. Afterward, enzyme-linked immunosorbent assay (ELISA) kits were used to estimate the concentrations of CTX-1, Fibulin-1, and vitamin D3. Additionally, LDH and albumin levels were determined using the automated biochemistry analyzer.
RESULTS
This study revealed that the majority of patients with multiple myeloma are between the ages of 51 and 60 years. The serum concentrations of CTX-1, Fibulin-1, and LDH were significantly increased in the multiple myeloma patients compared to the healthy control group. In contrast, the serum level of vitamin D3 was significantly decreased in patients with MM.
CONCLUSION
Our results indicate that the incidence of multiple myeloma is higher in males than in females. Additionally, the serum concentrations of CTX-1 and Fibulin-1 were significantly higher in the multiple myeloma patients compared to the healthy control group, indicating their potential for early detection and as therapeutic targets.
Topics: Humans; Multiple Myeloma; Female; Male; Middle Aged; Adult; Case-Control Studies; Calcium-Binding Proteins; Biomarkers, Tumor; Prognosis; Follow-Up Studies; Collagen Type I; Peptides; Peptide Fragments
PubMed: 38809631
DOI: 10.31557/APJCP.2024.25.5.1599 -
Jornal Brasileiro de Pneumologia :... May 2024
Topics: Humans; Multiple Myeloma; Amyloidosis; Bronchial Diseases; Tracheal Diseases; Male; Tomography, X-Ray Computed; Middle Aged; Bronchoscopy; Aged; Female; Biopsy
PubMed: 38808833
DOI: 10.36416/1806-3756/e20240080 -
Blood Cancer Journal May 2024Multiple myeloma (MM) therapeutics have evolved tremendously in recent years, with significant improvement in patient outcomes. As newer treatment options are developed,...
Multiple myeloma (MM) therapeutics have evolved tremendously in recent years, with significant improvement in patient outcomes. As newer treatment options are developed, stem cell transplant (SCT) remains an important modality that provides excellent disease control and delays the progression of disease. Over the years, SCT use has increased overall in the U.S., but two distinct gaps remain, including suboptimal use overall and racial-ethnic disparities. We evaluated the National Cancer Database (NCDB) to study what sociodemographic factors might play a role within a given racial-ethnic group leading to disparate SCT utilization, such that targeted approaches can be developed to optimize SCT use for all. In nearly 112,000 cases belonging to mutually exclusive categories of non-Hispanic Whites (NHW), non-Hispanic Blacks (NHB), Hispanics, non-Hispanic Asians (NHA), and others, we found certain factors including age, comorbidity index, payor type, facility type (academic vs. community) and facility volume to be uniformly associated with SCT use for all the racial-ethnic groups, while gender was not significant for any of the groups. There were several other factors that had a differential impact on SCT utilization among the various race-ethnicity groups studied, including year of diagnosis (significant for NHW, NHB, and Hispanics), income level (significant for NHW and Hispanics), literacy level (significant for NHW and NHB), and geographic location of the treatment facility (significant for NHW and NHA). The suboptimal SCT utilization overall in the U.S. suggests that there may be room for improvement for all, even including the majority NHW, while we continue to work on factors that lead to disparities for the traditionally underserved populations. This study helps identify sociodemographic factors that may play a role specifically in each group and paves the way to devise targeted solutions such that resource utilization and impact can be maximized.
Topics: Humans; Multiple Myeloma; Male; Female; Healthcare Disparities; Middle Aged; Aged; United States; Adult; Stem Cell Transplantation; Hematopoietic Stem Cell Transplantation
PubMed: 38806475
DOI: 10.1038/s41408-024-01067-x -
Blood Advances May 2024
Topics: Multiple Myeloma; Humans; Mesenchymal Stem Cells; Animals
PubMed: 38805218
DOI: 10.1182/bloodadvances.2024012705 -
Medical Sciences (Basel, Switzerland) May 2024Phospholipidosis is a rare disorder which consists of an excessive intracellular accumulation of phospholipids and the appearance of zebra bodies or lamellar bodies when... (Review)
Review
Double Hit of Hydroxichloroquine and Amiodarone Induced Renal Phospholipidosis in a Patient with Monoclonal Gammopathy and Sclerodermiform Syndrome: A Case Report and Review of the Literature.
Phospholipidosis is a rare disorder which consists of an excessive intracellular accumulation of phospholipids and the appearance of zebra bodies or lamellar bodies when looking at them using electron microscopy. This disease is associated with certain genetic diseases or is secondary to drugs or toxins. Drug-induced phospholipidosis encompasses many types of pharmaceuticals, most notably chloroquine, amiodarone or ciprofloxacin. Clinically and histologically, renal involvement can be highly variable, with the diagnosis not being made until the zebra bodies are seen under an electron microscope. These findings may require genetic testing to discount Fabry disease, as its histological findings are indistinguishable. Most of the chemicals responsible are cationic amphiphilic drugs, and several mechanisms have been hypothesized for the formation of zebra bodies and their pathogenic significance. However, the relationship between drug toxicity and phospholipid accumulation, zebra bodies and organ dysfunction remains enigmatic, as do the renal consequences of drug withdrawal. We present, to our knowledge, the first case report of acute renal injury with a monoclonal gammopathy of renal significance, lesions, and sclerodermiform syndrome, with zebra bodies that were associated with the initiation of a hydroxychloroquine and amiodarone treatment, as an example of drug-induced-phospholipidosis.
Topics: Humans; Acute Kidney Injury; Amiodarone; Hydroxychloroquine; Lipidoses; Paraproteinemias; Phospholipids; Female; Aged
PubMed: 38804381
DOI: 10.3390/medsci12020025