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Heliyon Jan 2024Human trabecular meshwork cell (HTMC) dysfunction results in imbalanced aqueous humor inflow and outflow, leading to an increase in intraocular pressure (IOP)....
PURPOSE
Human trabecular meshwork cell (HTMC) dysfunction results in imbalanced aqueous humor inflow and outflow, leading to an increase in intraocular pressure (IOP). Uncontrolled high IOP can promote the occurrence of glaucoma, an irreversible optic neuropathy. Here, we explored whether the long non-coding RNA plasmacytoma variant translocation 1 (lncRNA PVT1)/microRNA-29a-3p (miR-29a-3p) axis could ameliorate HTMC dysfunction under oxidative stress by modulating the expression of the proangiogenic factor vascular endothelial growth factor (VEGFA) and the profibrotic factor metalloproteinase-2 (MMP-2).
METHODS
HTMCs were cultured under HO-induced oxidative stress for 48 h. The expression of lncRNA PVT1, miR-29a-3p, VEGFA, MMP-2, intracellular adhesion molecule-1 (ICAM-1), and alpha-smooth muscle actin (α-SMA) was detected by reverse transcription quantitative real-time polymerase chain reaction, western blotting, and immunofluorescence. Interference experiments were conducted the transfection of HTMCs with small interfering RNA (siRNA) targeting lncRNA PVT1 or miR-29a-3p mimics. A luciferase reporter assay was undertaken to identify the presence of a miR-29a-3p binding site in lncRNA PVT1. Flow cytometry and Transwell and Cell Counting Kit-8 assays were employed to evaluate HTMC functions under oxidative stress with different treatments.
RESULTS
In HTMCs, the expression of lncRNA PVT1 was induced by HO treatment, whereas that of miR-29a-3p was inhibited. The levels of angiogenic factors (VEGFA, ICAM-1) and fibrosis-associated mediators (MMP-2, α-SMA) were upregulated in HTMCs under oxidative stress. The siRNA-mediated suppression of lncRNA PVT1 or the upregulation of miR-29a-3p significantly suppressed the expression of VEGFA, MMP-2, ICAM-1, and α-SMA. A luciferase reporter assay confirmed that lncRNA PVT1 directly targeted miR-29a-3p and acted as a miR-29a-3p sponge. The knockdown of lncRNA PVT1 restored the level of miR-29a-3p in HO-treated HTMCs, thereby inhibiting VEGFA and MMP-2, its target mRNAs. HTMC dysfunction, including increased apoptosis and decreased cell mobility and viability, could be effectively ameliorated by lncRNA PVT1 downregulation or miR-29a-3p overexpression under oxidative stress.
CONCLUSION
LncRNA PVT1 has potential as a therapeutic target for inhibiting VEGFA and MMP-2, thus protecting HTMCs, suppressing the progression of fibrosis, and, consequently, improving the outcome of glaucoma filtration surgery.
PubMed: 38173510
DOI: 10.1016/j.heliyon.2023.e23607 -
World Journal of Clinical Cases Aug 2023Multiple myeloma (MM) is a common hematologic malignancy that originates from a malignant clone of plasma cells. Solitary plasmacytoma, history of diabetes, and platelet...
BACKGROUND
Multiple myeloma (MM) is a common hematologic malignancy that originates from a malignant clone of plasma cells. Solitary plasmacytoma, history of diabetes, and platelet count are considered as prognostic factors for MM. But some patients are still associated with much worse outcomes without any prognostic predictors. This study aimed to observe the reduction rate of monoclonal protein (M protein) after the first and fourth chemotherapy cycles, which is considered as a new prognostic factor for progression-free survival (PFS) in standard-risk group of newly diagnosed MM patients.
AIM
To investigate the reduction rate of M protein after first and fourth cycle chemotherapy as a useful prognostic factor.
METHODS
A total of 316 patients diagnosed with MM for the first time between 2010 and 2019 at the Lishui Municipal Central Hospital were included. All patients were diagnosed according to the National Comprehensive Cancer Network (NCCN) 2020.V1 diagnostic criteria. The risk assessment was performed by the Mayo Stratification for Macroglobulinemia and Risk-Adapted Therapy guidelines. After diagnosis, 164 patients were evaluated and underwent treatment with four to eight courses of continuous induction chemotherapy. The patients with no response after induction treatment were administered additional therapy following the NCCN 2020.V1 criteria. The following baseline data from the patients were collected: Gender, age at diagnosis, Durie-Salmon stage, glutamic-pyruvic transaminase, glutamic-oxaloacetic transaminase, catabolite activator protein, albumin/globulin ratio, lactate dehydrogenase, translocation (t)(6;14), t(11;14), maintenance regimen, total cholesterol (TC), triglyceride, and phosphorous. All baseline data and the reduction rate of M protein after each chemotherapy cycle from the first to fourth were assessed by univariate analysis. The factors influencing the overall survival and PFS were then assessed by multivariate analysis. We found the first cycle (C1) reduction rate and the fourth cycle (C4) reduction rate as predictors of PFS. Then, PFS was compared between patients with a C1 reduction rate of M protein of ≥ 25% < 25% and ≥ 50% < 50%, and between patients with a C4 reduction rate of ≥ 25% < 25%, ≥ 50% < 50%, and ≥ 75% < 75%.
RESULTS
Multivariate analysis revealed age [hazard ratio (HR): 1.059, 95% confidence interval (95%CI): 1.033-1.085, ≤ 0.001], International Staging System stage (HR: 2.136, 95%CI: 1.500-3.041, ≤ 0.001), autotransplantion (HR: 0.201, 95%CI: 0.069-0.583, = 0.019), TC (HR: 0.689, 95%CI: 0.533-0.891, = 0.019), C1 reduction rate (HR: 0474, 95%CI: 0.293-0.767, = 0.019), and C4 reduction rate (HR: 0.254, 95%CI: 0.139-0.463, = 0.019) as predictors of PFS. The Kaplan-Meier survival analysis and the log-rank tests revealed that a higher reduction rate of M protein after first cycle (≥ 50%) and fourth cycle (≥ 75%) chemotherapy was associated with a longer PFS than the lower one.
CONCLUSION
Higher reduction rates of M protein after the first and fourth chemotherapy cycles can act as advantageous prognostic factors for PFS in standard-risk group of MM patients during initial diagnosis.
PubMed: 37727707
DOI: 10.12998/wjcc.v11.i24.5643 -
Current Problems in Cancer Jun 2024A solitary plasmacytoma is classified into a solitary plasmacytoma of the bone (SBP) and a solitary extramedullary (soft tissue mass) plasmacytoma, based on the site of...
BACKGROUND
A solitary plasmacytoma is classified into a solitary plasmacytoma of the bone (SBP) and a solitary extramedullary (soft tissue mass) plasmacytoma, based on the site of the lesion. Despite the high local control rate with radiotherapy, approximately half of patients' conditions progress to multiple myeloma (MM) within 3-5 years after diagnosis, with SBP having a worse prognosis.
PATIENTS AND METHODS
We retrospectively assessed the treatment and outcomes of patients with SBP in a hospital in China from 2008 to 2021. Twenty-four patients treated over 13 years with SBP were enrolled in this retrospective study.
RESULTS
The most common sites for SBP were the axial skeleton and femur. The M protein was detected in 11 patients (46 %), of which 8 (33 %) had light chains, 2 (8 %) had immunoglobulin G kappa and 1 (4 %) had immunoglobulin D kappa. Flow cytometry revealed that 5 patients (21 %) had minimal bone marrow involvement. The treatment included chemotherapy, surgery, and radiotherapy in 18 (75 %), 12 (50 %), and 9 (38 %) patients, respectively, of whom 13 (54 %) received combined treatment. Over a median follow-up period of 67.2 months, 9 patients (38 %) developed MM in a median time of 101.5 months. The 5- and 10-year progression-free survival rates were 67.3 % and 37.4 %, respectively. One patient died due to pneumonia without progression and the other died due to relapse.
CONCLUSION
This study confirmed the high rate of progression of SBP to MM, indicating a need for adjunct chemotherapy for the management of SBP.
Topics: Humans; Plasmacytoma; Middle Aged; Male; Female; Retrospective Studies; Aged; Bone Neoplasms; Adult; Prognosis; Survival Rate; Follow-Up Studies; China; Combined Modality Therapy
PubMed: 38598973
DOI: 10.1016/j.currproblcancer.2024.101095 -
Solitary Plasmacytoma of the Spine in a Young Male and the Outcome of Inpatient Rehabilitation Stay.Cureus Sep 2023Solitary plasmacytoma (SP) can be classified into two groups: a solid mass of neoplastic monoclonal plasma cells in bone, also called a solitary bone plasmacytoma (SBP),...
Solitary plasmacytoma (SP) can be classified into two groups: a solid mass of neoplastic monoclonal plasma cells in bone, also called a solitary bone plasmacytoma (SBP), or less likely solitary extramedullary plasmacytoma (SEP) without any evidence of systemic disease of multiple myeloma. The diagnosis should be made by biopsy confirmation, revealing monoclonal plasma cell infiltration from the mass. The SBP usually affects the axial skeleton. Males have a higher incidence than females, as the ratio is 2/1, and the average age is 55. SP incidence usually increases with age. SBP has a significantly higher risk for progression to myeloma, usually within two years, and radiotherapy (RT) is the treatment of choice. Patients with acute declining neurologic dysfunction require urgent surgery before radiation therapy. We report a middle-aged man who presented with bilateral lower extremity weakness. Thoracic MRI with and without contrast revealed a large soft tissue and osseous mass centered at the T8 vertebral body with a large paravertebral extension, causing spinal cord compression at the T8-T9 level. The patient's clinical presentation, assessment, and rehabilitation management are discussed. Patients with this diagnosis are not properly diagnosed for approximately six months.
PubMed: 37868411
DOI: 10.7759/cureus.45673 -
Cureus Dec 2023We present a rare case of a solitary intracranial plasmacytoma of the brain parenchyma in a 49-year-old female who presented with neck pain/headache, paresthesias, and...
We present a rare case of a solitary intracranial plasmacytoma of the brain parenchyma in a 49-year-old female who presented with neck pain/headache, paresthesias, and auditory hallucinations. A workup revealed a solitary left parietal lobe brain lesion and a biopsy demonstrated a plasma cell infiltrate consistent with an extramedullary plasmacytoma. A complete workup for multiple myeloma was negative. As opposed to surgical resection and adjuvant radiation therapy (RT), as described in prior case reports in the literature, this patient was managed with definitive local RT alone to 50 Gy in 25 fractions. Six months following primary RT completion, the patient's presenting symptoms completely resolved and follow-up imaging revealed regression of the primary tumor. To our knowledge, this is the first reported case of a solitary extramedullary plasmacytoma of the brain treated with localized definitive RT alone.
PubMed: 38161554
DOI: 10.7759/cureus.49798 -
Indian Journal of Thoracic and... Nov 2023Diagnostic dilemma, owing to the inconclusiveness of biopsy results, often leaves us with limited options to offer to the patients upfront, amongst the various...
Diagnostic dilemma, owing to the inconclusiveness of biopsy results, often leaves us with limited options to offer to the patients upfront, amongst the various armamentarium available. We hereby report a rare case of extramedullary plasmacytoma, whose diagnosis was established only on the final histopathology report with the aid of immunohistochemistry. A 50-year-old gentleman presented to our outpatient setup with computed tomography suggestive of a well-defined endobronchial mass occupying the left lower lobe bronchus. However, bronchoscopy and computed tomography-guided biopsies were inconclusive. After a routine metastatic workup, the patient underwent a left lower lobectomy following a provisional diagnosis of carcinoid on the frozen section. The final histopathology was solitary endobronchial plasmacytoma. Postoperative myeloma workup was within normal limits and the patient is doing well and disease free at 8 months of follow-up. This rare differential needs to be kept in mind while evaluating a case of well-defined endobronchial growth.
PubMed: 37885935
DOI: 10.1007/s12055-023-01557-w -
Monaldi Archives For Chest Disease =... Jul 2023Extramedullary involvement in multiple myeloma is uncommon. It can present as a plasma cell mass in the soft tissue surrounding the bony structures through direct...
Extramedullary involvement in multiple myeloma is uncommon. It can present as a plasma cell mass in the soft tissue surrounding the bony structures through direct extension or in various other organs via hematogenous spread. Here, we report a case of paraskeletal plasmacytoma that manifested as a chest wall mass in a 60-year-old man.
PubMed: 37522859
DOI: 10.4081/monaldi.2023.2637 -
Journal of Investigative Medicine High... 2024Plasmacytoma is a rare plasma cell dyscrasia that grows in bones or soft tissues such as the pharynx. Soft tissue plasmacytomas are rare, and a higher burden has been...
Plasmacytoma is a rare plasma cell dyscrasia that grows in bones or soft tissues such as the pharynx. Soft tissue plasmacytomas are rare, and a higher burden has been reported in the upper aero-digestive tract, often manifesting as hoarseness, dysphagia, or odynophagia. Due to their rarity, extramedullary plasmacytomas (EMPs) have unknown prognostic factors, and guidelines for optimal management are still lacking. However, radiation therapy and surgery have been used with positive outcomes. Herein, we describe a unique case of plasmacytoma of the pharyngeal tissue in a male patient with a history of HIV disease. The patient completed 28 sessions of radiation therapy, resulting in an improvement in his throat pain and hoarseness. Given the patient's age and lack of traditional risk factors for head and neck cancers, his hoarseness and odynophagia proved to be a diagnostic conundrum. Although infrequent, soft tissue plasmacytomas should be considered in the differential diagnosis of head and neck tumors.
Topics: Humans; Male; Plasmacytoma; Pharynx; Hoarseness; Head and Neck Neoplasms
PubMed: 38577756
DOI: 10.1177/23247096241242237 -
Journal of Microscopy and Ultrastructure 2024The study aims to categorize malignant small round cell tumors (MSRCTs) originating in various sites of the body with the objective of utilization of cytomorphological...
AIM AND OBJECTIVES
The study aims to categorize malignant small round cell tumors (MSRCTs) originating in various sites of the body with the objective of utilization of cytomorphological features and ancillary techniques.
STUDY DESIGN
It is a cross-sectional study conducted over a time span of 3 years (2017-2020). 33 cases of tumors with round cell morphology were evaluated by fine needle aspiration cytology (FNAC).
MATERIALS AND METHODS
The application of cell block preparation supported by immunohistochemistry aided in the categorization of 23 cases with definite diagnosis and the rest were reported as MSRCTs.
RESULTS
Among the categorized 23/33 cases, the most common diagnosis was Ewing's sarcoma (7/23) followed by 6 cases of lymphoma. There were 2 cases each of rhabdomyosarcoma and Langerhans cell histiocytosis (LCH) and 1 case each of neuroblastoma, desmoplastic small round cell tumor (DSRCT), myeloid sarcoma, neuroendocrine tumor of pancreas, plasmacytoma, and small cell carcinoma. Histopathology confirmation was available in 24/33 cases. Among the categorized tumors (23/33), biopsy correlation was available in 19 cases, of which concordant result was seen in 17 cases (89.47%), which were 6 cases of lymphoma, 5 cases of Ewing's sarcoma (EWS), 2 of rhabdomyosarcoma, and 1 each of neuroblastoma, small cell carcinoma, DSRCT, and LCH. Discordant result was seen in one case of rhabdomyosarcoma and a case of synovial sarcoma reported as extraskeletal EWS in cytology. Out of the uncategorized cases reported as MSRTCs, histopathology was available in 5 cases which were diagnosed as rhabdomyosarcoma (1 cases), lymphoma (1 case), amelanotic melanoma (1 case), and extraskeletal EWS (2 cases).
CONCLUSION
Categorization of MSRCTs should be done to implement appropriate therapeutic protocol. FNAC provides a rapid diagnosis contributing immensely for the timely management of the patient. Detailed cytomorphological evaluation serves as a guide for further evaluation by ancillary techniques leading to definitive diagnosis.
PubMed: 38633566
DOI: 10.4103/jmau.jmau_66_21 -
The British Journal of Dermatology Feb 2024
Topics: Humans; Carcinoma, Squamous Cell; RNA, Long Noncoding; Plasmacytoma; Skin Neoplasms; Cell Line, Tumor
PubMed: 38366829
DOI: 10.1093/bjd/ljae031