-
Advanced Materials (Deerfield Beach,... Oct 2023The prognosis in cases of pancreatic ductal adenocarcinoma (PDAC) with current treatment modalities is poor owing to the highly desmoplastic tumor microenvironment...
The prognosis in cases of pancreatic ductal adenocarcinoma (PDAC) with current treatment modalities is poor owing to the highly desmoplastic tumor microenvironment (TME). Herein, a β-glucans-functionalized zinc-doxorubicin nanoparticle system (βGlus-ZnD NPs) that can be orally administered, is developed for targeted PDAC therapy. Following oral administration in PDAC-bearing mice, βGlus-ZnD NPs actively target/transpass microfold cells, overcome the intestinal epithelial barrier, and then undergo subsequent phagocytosis by endogenous macrophages (βGlus-ZnD@Mϕ). As hitchhiking cellular vehicles, βGlus-ZnD@Mϕ transits through the intestinal lymphatic system and enters systemic circulation, ultimately accumulating in the tumor tissue as a result of the tumor-homing and "stealth" properties that are conferred by endogenous Mϕ. Meanwhile, the Mϕ that hitchhikes βGlus-ZnD NPs is activated to produce matrix metalloproteinases, destroying the desmoplastic stromal barrier, and differentiates toward the M -like phenotype, modulating the TME and recruiting effector T cells, ultimately inducing apoptosis of the tumor cells. The combination of βGlus-ZnD@Mϕ and immune checkpoint blockade effectively inhibits the growth of the primary tumor and suppresses the development of metastasis. It thus represents an appealing approach to targeted PDAC therapy.
Topics: Animals; Mice; beta-Glucans; Pancreatic Neoplasms; Macrophages; Carcinoma, Pancreatic Ductal; Tumor Microenvironment
PubMed: 37363886
DOI: 10.1002/adma.202304735 -
Cutis May 2021Desmoplastic melanoma (DMM) is a rare variant of melanoma that presents major diagnostic challenges. It can mimic both benign or other malignant tumors and may be easily...
Desmoplastic melanoma (DMM) is a rare variant of melanoma that presents major diagnostic challenges. It can mimic both benign or other malignant tumors and may be easily confused by clinicians and pathologists. We report a patient who presented with a pink-colored papule on the left lateral neck. Histopathology revealed a nodular spindle cell tumor in the dermis resembling a neurofibroma at low power. However, higher-power evaluation and the use of immunohistochemical staining confirmed the diagnosis of DMM.We present this case to highlight the ongoing challenges of diagnosing DMM both clinically and histologically and to review the salient features of this often benign-appearing tumor. Advancing age, male gender, and head and neck location are associated with an increased risk of DMM-specific death. It is important that new or changing lesions in the correct cohort and location are biopsied promptly.
Topics: Humans; Male; Melanoma; Neurofibroma; Skin Neoplasms
PubMed: 34288854
DOI: 10.12788/cutis.0241 -
Thoracic Cancer Nov 2021Desmoplastic fibroblastoma is an extremely rare benign soft tissue tumor and desmoplastic fibroblastoma originating from the diaphragm has not been documented...
Desmoplastic fibroblastoma is an extremely rare benign soft tissue tumor and desmoplastic fibroblastoma originating from the diaphragm has not been documented previously. In our case, we report the first primary diaphragm desmoplastic fibroblastoma.
Topics: Diagnosis, Differential; Diaphragm; Female; Fibroma, Desmoplastic; Humans; Middle Aged; Soft Tissue Neoplasms; Tomography, X-Ray Computed
PubMed: 34581000
DOI: 10.1111/1759-7714.14168 -
Frontiers in Oncology 2023Development of successful antibody-based immunotherapeutic and radioimmunotherapeutic strategies rely on the identification of cell surface tumor-associated antigens...
BACKGROUND
Development of successful antibody-based immunotherapeutic and radioimmunotherapeutic strategies rely on the identification of cell surface tumor-associated antigens (TAA) with restricted expression on normal tissues. Desmoplastic small round cell tumor (DSRCT) is a rare and generally neglected malignancy that primarily affects adolescent and young adult males. New therapies capable of treating disseminated disease are needed for DSRCT, which is often widespread at diagnosis.
METHODS
We used immunohistochemistry (IHC) on fresh frozen surgical specimens and patient-derived xenograft (PDX) tumors and flow cytometry on DSRCT cell lines to evaluate expression of TAAs in these tumors. cytotoxicity assays were used to evaluate the efficacy of T cell-engaging bispecific antibodies (T-BsAbs) directed at these targets. , we used an intraperitoneal xenograft mouse model of DSRCT to test T-BsAbs against several TAAs.
RESULTS
In DSRCT specimens we found widespread expression of B7-H3, EGFR, GD2, HER2, mesothelin, and polysialic acid, clinical targets for which specific antibody therapeutics are available. The expression of B7-H3, EGFR, HER2, and mesothelin was confirmed on the cell surface of DSRCT cell lines. cytotoxicity assays confirmed the efficacy of T cell-engaging bispecific antibodies (T-BsAbs) directed at these targets against DSRCT cells. Remarkably, a HER2xCD3 T-BsAb was capable of completely shrinking established tumors in an intraperitoneal mouse model of DSRCT.
CONCLUSIONS
We propose that these TAAs should be further investigated in preclinical models as targets for immunotherapy and radioimmunotherapy with the hope of providing a rationale to extend these therapies to patients with advanced DSRCT.
PubMed: 37091153
DOI: 10.3389/fonc.2023.1104693 -
World Journal of Surgical Oncology Jun 2021Desmoplastic small round cell tumor (DSRCT) is a highly malignant sarcoma that occurs in the abdominopelvic cavities of adolescents. The accurate diagnosis of DSRCT is... (Review)
Review
BACKGROUND AND PURPOSE
Desmoplastic small round cell tumor (DSRCT) is a highly malignant sarcoma that occurs in the abdominopelvic cavities of adolescents. The accurate diagnosis of DSRCT is challenging owing to limited literatures. Our study aimed to investigate the relationship between clinicopathological features and prognosis in patients with DSRCTs.
METHODS
Data of 8 patients with DSRCT originating from the abdominal cavity were retrospectively reviewed. The clinical manifestations, pathological characteristics, treatment approaches, and prognosis were analyzed. The histopathological (identified using hematoxylin-eosin staining), immunohistochemical, and molecular diagnostic (using fluorescence in situ hybridization) features were also reviewed.
RESULTS
All patients were male aged between 24 and 45 years (median age, 30 years). The main clinical symptoms included abdominal distension, abdominal pain, and constipation. Seven of the 8 patients developed metastases to either distant organs or lymph nodes. Multiple gray nodules with diameters of 1-10 cm and poorly defined boundaries were scattered throughout the omentum and mesentery. Histopathological examination demonstrated well-defined nests composed of small round blue cells separated by markedly desmoplastic stroma. Immunohistochemical analysis revealed positive expressions of desmin, vimentin and C-terminal of Wilm's tumor suppressor (WT-1). The Ewing sarcoma breakpoint region 1 gene fused with WT1 (EWSR1-WT1) gene fusion was detected in all patients. Cytoreductive surgery (CRS) was performed in 6 patients. Follow-up period ranged from 7.5 to 28.5 months with a median of 17.2 months. Three patients died during follow-up.
CONCLUSION
DSRCT is highly aggressive and presents distinctive morphological features. CRS is the essential therapy for DSRCT. A test for the combined expression of desmin, cytokeratins, and C-terminal of WT-1, as well as the analysis of morphologic features, might be helpful during DSRCT diagnosis, and the EWSR1-WT1 gene fusion is the gold standard for definitive diagnosis. Our work will provide new insights into the diagnosis and treatment of DSRCTs.
Topics: Adolescent; Adult; Desmoplastic Small Round Cell Tumor; Humans; In Situ Hybridization, Fluorescence; Kidney Neoplasms; Male; Middle Aged; Oncogene Proteins, Fusion; Prognosis; Retrospective Studies; Young Adult
PubMed: 34193155
DOI: 10.1186/s12957-021-02310-6 -
Cureus Oct 2022Primary desmoplastic small round cell tumor (DSRCT) in the head and neck region is extremely rare. There is limited information about its clinicopathological... (Review)
Review
Primary desmoplastic small round cell tumor (DSRCT) in the head and neck region is extremely rare. There is limited information about its clinicopathological characteristics, prognosis, and treatment modalities. The purpose of this study is to provide a comprehensive review of DSRCT occurring primarily in the head and neck, to demonstrate its peculiar morphology and immunohistochemical expression, and to address the differential diagnoses. A total of 25 cases were collected after a thorough review of the relevant literature. DSRCT was most frequently reported in the major salivary glands, followed by the eyes. Furthermore, some cases were misinterpreted as poorly differentiated carcinoma, Ewing sarcoma, and olfactory neuroblastoma. Diagnosing DSRCTs in the head and neck can be very challenging due to their rarity in this location, overlapping morphology, and immunohistochemistry. In these cases, following a systemic approach helps to solve diagnostic problems.
PubMed: 36415387
DOI: 10.7759/cureus.30475 -
Current Oncology Reports Oct 2022Mesenteric desmoplasia in small intestinal neuroendocrine neoplasms (SINENs) is associated with increased morbidity and mortality. In this paper, we discuss the... (Review)
Review
PURPOSE OF REVIEW
Mesenteric desmoplasia in small intestinal neuroendocrine neoplasms (SINENs) is associated with increased morbidity and mortality. In this paper, we discuss the development of desmoplasia in SINENs.
RECENT FINDINGS
The fibrotic reactions associated with these tumours could be limited to the loco-regional environment of the tumour and/or at distant sites. Mesenteric fibrotic mass forms around a local lymph node. Formation of desmoplasia is mediated by interactions between the neoplastic cells and its microenvironment via number of profibrotic mediators and signalling pathways. Profibrotic molecules that are mainly involved in the desmoplastic reaction include serotonin, TGFβ (transforming growth factor β) and CTGF (connective tissue growth factor), although there is some evidence to suggest that there are a number of other molecules involved in this process. Desmoplasia is a result of autocrine and paracrine effects of multiple molecules and signalling pathways. However, more research is needed to understand these mechanisms and to develop targeted therapy to minimise desmoplasia.
Topics: Fibrosis; Humans; Intestinal Neoplasms; Neuroendocrine Tumors; Signal Transduction; Tumor Microenvironment
PubMed: 35554845
DOI: 10.1007/s11912-022-01211-5 -
Acta Pharmaceutica Sinica. B Nov 2020Desmoplastic tumors have an abundance of stromal cells and the extracellular matrix which usually result in therapeutic resistance. Current treatment prescriptions for... (Review)
Review
Desmoplastic tumors have an abundance of stromal cells and the extracellular matrix which usually result in therapeutic resistance. Current treatment prescriptions for desmoplastic tumors are usually not sufficient to eliminate the malignancy. Recently, through modulating cancer-associated fibroblasts (CAFs) which are the most abundant cell type among all stromal cells, natural products have improved chemotherapies and the delivery of nanomedicines to the tumor cells, showing promising ability to improve treatment effects on desmoplastic tumors. In this review, we discussed the latest advances in inhibiting desmoplastic tumors by modeling CAFs using natural products, highlighting the potential therapeutic abilities of natural products in targeting CAFs for cancer treatment.
PubMed: 33304782
DOI: 10.1016/j.apsb.2020.04.005 -
Journal of Surgical Oncology Feb 2022
Topics: Humans; Immune Checkpoint Inhibitors; Melanoma; Neoplasm Recurrence, Local; Sentinel Lymph Node Biopsy; Skin Neoplasms
PubMed: 34535908
DOI: 10.1002/jso.26677 -
In Vivo (Athens, Greece) 2021Desmoplastic fibroblastoma (also known as collagenous fibroma) is an uncommon benign fibroblastic/myofibroblastic neoplasm that primarily arises in the subcutaneous... (Review)
Review
Desmoplastic fibroblastoma (also known as collagenous fibroma) is an uncommon benign fibroblastic/myofibroblastic neoplasm that primarily arises in the subcutaneous tissue of upper extremity. Magnetic resonance imaging reveals a well-defined mass in intimate association with dense connective tissue and prominent low signal intensity on all pulse sequences. Peripheral and septal enhancement is usually seen after intravenous contrast. Histologically, the lesion is paucicellular and consists of spindle to stellate-shaped cells embedded in a collagenous or myxocollagenous stroma with low vascularity. Diffuse and strong nuclear immunoreactivity for FOS-like antigen 1 seems to be characteristic of desmoplastic fibroblastoma. Cytogenetic studies have demonstrated the presence of 11q12 rearrangements and an identical t(2;11)(q31;q12) translocation. This review provides an updated overview of the clinical, radiological, histological, cytogenetic and molecular genetic features of desmoplastic fibroblastoma and discusses the relationship to fibroma of tendon sheath.
Topics: Fibroma; Fibroma, Desmoplastic; Humans; Magnetic Resonance Imaging; Soft Tissue Neoplasms; Translocation, Genetic
PubMed: 33402451
DOI: 10.21873/invivo.12233