-
Acta Clinica Belgica Aug 2023Mastocytosis is a complex heterogenous multisystem disorder that is characterized by pathologic activation or accumulation of neoplastic mast cells (MCs) in one or more... (Review)
Review
Mastocytosis is a complex heterogenous multisystem disorder that is characterized by pathologic activation or accumulation of neoplastic mast cells (MCs) in one or more organs. This clonal MC expansion is often associated with a somatic gain-of-function mutation (D816V in most of the cases) in the KIT gene, encoding for the MC surface receptor KIT (CD117), a stem cell growth factor receptor. Based on clinical and biochemical criteria, the World Health Organization (WHO) divided mastocytosis into different subclasses. The exact prevalence of mastocytosis remains elusive, but it is estimated that the disease affects approximately 1 in 10,000 persons. The clinical presentation of mastocytosis varies significantly, ranging from asymptomatic patients to a life-threatening disease with multiple organ involvement, potentially leading to cytopenia, malabsorption, hepatosplenomegaly, lymphadenopathy, ascites or osteolytic bone lesions with pathological fractures. Patients with mastocytosis may experience symptoms related to release of MC mediators, such as flushing or diarrhea or even more severe symptoms such as anaphylaxis. Recently, a new genetic trait, hereditary alpha tryptasemia (HaT), was described which involves a copy number variation in the TPSAB1-gene. Its role as standalone multisystem syndrome is heavily debated. There is emerging evidence suggesting there might be a link between HaT and due to the increased prevalence of HaT in patients with SM. The aim of this review is to provide a practical roadmap for diagnosis and management of mastocytosis and its associated entities, since there are still many misconceptions about these topics. AdvSM: Advanced systemic mastocytosis; ASM: Aggressive systemic mastocytosis; aST: acute serum tryptase; BM: Bone marrow; BMM: Bone marrow mastocytosis; bST: baseline serum tryptase; CM: Cutaneous mastocytosis; DCM: Diffuse cutaneous mastocytosis; HVA: Hymenoptera venom allergy; HaT: Hereditary alpha tryptasemia; ISM: Indolent systemic mastocytosis; MC: Mast cell; MCA: Mast cell activation; MCAS: Mast cell activation syndrome; MCL: Mast cell leukemia; MIS: Mastocytosis in the skin; MMAS: Monoclonal mast cell activation syndrome; MPCM: Maculopapular cutaneous mastocytosis; SM: Systemic mastocytosis; SM-AHN: Systemic mastocytosis with associated hematological neoplasm; SSM: Smouldering systemic mastocytosis; VIT: Venom immunotherapy.
Topics: Humans; Mastocytosis, Systemic; Tryptases; DNA Copy Number Variations; Mastocytosis; Mastocytosis, Cutaneous
PubMed: 36259506
DOI: 10.1080/17843286.2022.2137631 -
Clinical Chemistry and Laboratory... Jun 2024Ascites is the pathological accumulation of fluid within the peritoneal cavity. It often occurs as results of liver cirrhosis, malignant neoplasia, tuberculous... (Review)
Review
Ascites is the pathological accumulation of fluid within the peritoneal cavity. It often occurs as results of liver cirrhosis, malignant neoplasia, tuberculous infection, cardiac insufficiency, renal diseases, etc. Determining the etiology is an essential step in the management of patients with new-onset ascites. Abdominal paracentesis with appropriate ascitic fluid analysis is probably the most cost-effective method of determining the cause of ascites. We performed a literature search of PubMed and identified articles published in the field of ascites, to evaluate diagnostic values of various parameters in defining the etiologies of ascites and then provides diagnostic algorithm for patients with new-onset ascites. In patients with ascites, the constituent ratio of underlying etiology varies between developed and developing countries. It is a challenge to define the etiologies of ascites in developing countries. Routine ascitic fluid analysis should include the serum ascites albumin gradient (SAAG), total protein concentration, cell count and differential. Optional ascitic fluid analysis includes cholesterol, fluid culture, cytology, tumor markers, lactate dehydrogenase, adenosine deaminase (ADA), triglyceride, amylase, glucose, brain natriuretic peptide (BNP), etc. Our review evaluated diagnostic values of the above parameters in defining the etiologies of ascites. Diagnostic algorithm established in this review would provide a practical and convenient diagnostic strategy for clinicians in diagnosing patients with new-onset ascites.
Topics: Humans; Ascites; Ascitic Fluid; Algorithms; Diagnosis, Differential
PubMed: 38112289
DOI: 10.1515/cclm-2023-1112 -
Cell Reports Jan 2024Malignant ascites accompanied by peritoneal dissemination contain various factors and cell populations as well as cancer cells; however, how the tumor microenvironment...
Malignant ascites accompanied by peritoneal dissemination contain various factors and cell populations as well as cancer cells; however, how the tumor microenvironment is shaped in ascites remains unclear. Single-cell proteomic profiling and a comprehensive proteomic analysis are conducted to comprehensively characterize malignant ascites. Here, we find defects in immune effectors along with immunosuppressive cell accumulation in ascites of patients with gastric cancer (GC) and identify five distinct subpopulations of CD45(-)/EpCAM(-) cells. Mesothelial cells with mesenchymal features in CD45(-)/EpCAM(-) cells are the predominant source of chemokines involved in immunosuppressive myeloid cell (IMC) recruitment. Moreover, mesothelial-mesenchymal transition (MMT)-induced mesothelial cells strongly express extracellular matrix (ECM)-related genes, including tenascin-C (TNC), enhancing metastatic colonization. These findings highlight the definite roles of the mesenchymal cell population in the development of a protumorigenic microenvironment to promote peritoneal dissemination.
Topics: Humans; Ascites; Epithelial Cell Adhesion Molecule; Proteomics; Peritoneum; Peritoneal Neoplasms; Cell Line, Tumor; Tumor Microenvironment
PubMed: 38232734
DOI: 10.1016/j.celrep.2023.113613 -
International Immunopharmacology May 2024The Gustave Roussy Immune (GRIm) score predicts survival outcomes in several cancers. However, the prognostic significance of the GRIm score in patients with malignant...
BACKGROUNDS
The Gustave Roussy Immune (GRIm) score predicts survival outcomes in several cancers. However, the prognostic significance of the GRIm score in patients with malignant ascites has not yet been investigated.
METHODS
Clinical samples were collected from a cohort of patients with malignant ascites secondary to hepatocellular carcinoma (HCC). We calculated serum GRIm (sGRIm) and ascites GRIm (aGRIm) scores and divided the samples into low and high GRIm score groups. Survival analysis was used to compare the prognostic significance of the sGRIm and aGRIm scores. 16S rRNA sequencing was performed to determine the profiles of the intratumoral microbiota in the groups. A fluorescent multiplex immunohistochemistry (mIHC) assay was used to detect the expression of different immune cells by labeling seven markers of malignant ascites.
RESULTS
155 patients with HCC and malignant ascites were enrolled in this study. Survival analysis revealed that the aGRIm score showed a superior prognostic significance compared to the sGRIm score. Microbial analysis demonstrated that the bacterial richness and diversity were higher in the low aGRIm score group than in the high aGRIm score group. LefSe analysis revealed that certain bacteria were correlated with high aGRIm scores. Fluorescent mIHC displayed the tumor microenvironment of malignant ascites and found that the density of CD8 + T cells was significantly higher in the low aGRIm score group than in the high aGRIm score group.
CONCLUSIONS
Our present study identified a novel scoring system (aGRIm score) that can predict the survival outcome of patients with malignant ascites secondary to HCC.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Ascites; Female; Male; Middle Aged; Microbiota; Aged; Prognosis; Tumor Microenvironment; Adult; RNA, Ribosomal, 16S
PubMed: 38677092
DOI: 10.1016/j.intimp.2024.112097 -
Nutrition (Burbank, Los Angeles County,... Oct 2023Wasting in cancer patients has long been recognized as a condition that adversely affects cancer patients' quality of life, treatment tolerance, and oncological... (Review)
Review
Wasting in cancer patients has long been recognized as a condition that adversely affects cancer patients' quality of life, treatment tolerance, and oncological outcomes. Historically, this condition was mainly evaluated by changes in body weight. However, this approach is not quite accurate because body weight is the overall change of all body compartments. Conditions such as edema and ascites can mask the severity of muscle and adipose tissue depletion. Changes in body composition assessment in cancer patients have historically been underappreciated because of the limited availability of measurement tools. As more evidence highlighting the importance of body composition has emerged, it is imperative to apply a more precise evaluation of nutritional status and a more targeted approach to provide nutritional support for cancer patients. In this review, we will discuss the modalities for evaluating body composition and how to manage body composition changes in cancer patients.
Topics: Humans; Quality of Life; Neoplasms; Cachexia; Body Composition; Body Weight; Sarcopenia; Muscle, Skeletal
PubMed: 37441827
DOI: 10.1016/j.nut.2023.112132 -
BMC Women's Health Sep 2023Struma ovarii (SO) is a rare tumor and may transform into ovarian strumal carcinoid (OSC) and/or malignant struma ovarii (MSO), but the incidence, clinical...
BACKGROUND
Struma ovarii (SO) is a rare tumor and may transform into ovarian strumal carcinoid (OSC) and/or malignant struma ovarii (MSO), but the incidence, clinical characteristics, and survival outcomes have not been well defined.
METHODS
We conducted a retrospective study of patients with ovarian strumal diseases treated in the our hospital between 1980 and 2022. Subgroup analyses of SO, OSC, and MSO were subsequently performed.
RESULTS
A total of 275 cases (2.14%) were identified in a cohort of 12,864 patients with ovarian teratomas, where SO, OSC, and MSO accounted for 83.3%, 12.0%, and 4.7% of cases, respectively. There were no significant differences in age, tumor sizes, elevated tumor markers, and ascites among the three subgroups. At initial treatment, all patients with SO or OSC had FIGO stage I disease except one SO patient presenting metastatic disease, ten patients had MSO confined to the ovary, whereas other three patients had metastatic diseases. Two patients with SO respectively relapsed at peritoneum and anterior mesorectum, while none of the OSC patients presented tumor recurrence or death despite different surgical procedures employed. The 5-year recurrence-free survival rate was 88.9%, and only one death occurred at 9.5 years after diagnosis in patients with MSO. Radioiodine therapy showed satisfactory therapeutic efficacy, but these patients showed poor responses to the chemotherapy.
CONCLUSION
2.14% of ovarian teratoma could be classified as SO, of which 12.0% and 4.7% of SO may transform into OSC and MSO, repsectively. The survival outcomes were excellent even after SO transformed into OSC or MSO.
SYNOPSIS
SO occupied 2.14% of ovarian teratoma, where 12.0% and 4.7% of SO may transform into OSC and MSO, respectively, and had excellent survival outcomes.
Topics: Female; Humans; Ovarian Neoplasms; Struma Ovarii; Retrospective Studies; Carcinoid Tumor; Incidence; Iodine Radioisotopes; Neoplasm Recurrence, Local; Teratoma
PubMed: 37726744
DOI: 10.1186/s12905-023-02624-5 -
Internal Medicine (Tokyo, Japan) Aug 2023A 16-year-old Japanese girl developed a fever, thrombocytopenia, and renal dysfunction. Treatment was started with steroids, but cervical lymphadenopathy and ascites...
A 16-year-old Japanese girl developed a fever, thrombocytopenia, and renal dysfunction. Treatment was started with steroids, but cervical lymphadenopathy and ascites developed. A lymph node biopsy indicated TAFRO syndrome. The patient's renal function deteriorated, and dialysis was started. Refractory hypertension and subsequent encephalopathy developed. Treatment was started with an anti-IL-6 receptor antibody and an anti-CD20 monoclonal antibody. A kidney biopsy showed malignant nephrosclerosis-like microangiopathy and glomerular collapse due to narrowing of the small arteries. The majority of TAFRO syndrome cases are adult-onset, with glomerular microangiopathy. To our knowledge, this is the first report of adolescent-onset TAFRO syndrome presenting with malignant nephrosclerosis-like lesions associated with hypertension.
Topics: Adult; Female; Humans; Adolescent; Nephrosclerosis; Castleman Disease; Kidney Glomerulus; Kidney Diseases; Hypertension; Edema
PubMed: 36517029
DOI: 10.2169/internalmedicine.0529-22 -
Euphorbia factor L1 suppresses breast cancer liver metastasis via DDR1-mediated immune infiltration.Aging Sep 2023Euphorbia factor L1 (EFL1), a lathyrane-type diterpenoid from the medicinal herb Euphorbia lathyris L., has been documented to possess various pharmacologic actives....
Euphorbia factor L1 (EFL1), a lathyrane-type diterpenoid from the medicinal herb Euphorbia lathyris L., has been documented to possess various pharmacologic actives. However, the function of EFL1 on breast cancer is not clear. In this study, we explored the effect and mechanism of EFL1 on breast cancer liver metastasis. Female BALB/c mice were subjected to breast cancer-surgical hepatic implantation (SHI) to establish breast cancer liver metastasis model . At 10 days post-surgery, mice were administrated with EFL1 once daily for a total of 2 weeks. Serum AST and ALT activities, abdominal circumference, peritoneal fluid, tumor weight and volume were determined to assess liver and mesenteric re-metastasis of breast cancer. H&E staining was used to observe morphology changes in tumor, liver and small intestine tissues. ELISA was applied to observe inflammatory levels. Tumor DDR1 expression and immune infiltration were determined using western blotting, immunohistochemistry and flow cytometer methods. Our results showed that EFL1 administration improved liver function (AST and ALT activities), ascites, liver metastasis and mesenteric re-metastasis in SHI mice. Also, SHI-induced inflammatory cell infiltration and IL-1β, IL-6, TNF-α generation in ascites were decreased by EFL1 treatment. Mechanism study revealed that EFL1 intervention enhanced the ratios of CD4+ and CD8+ and CD49b+(NK) T lymphocytes and decreased Treg cells through downregulating DDR1 in the tumor of SHI mice. Furthermore, overexpression of DDR1 abolished the anti-liver metastasis effect and pro-immune infiltration action of EFL1 in SHI mice. Together, our findings suggested that EFL1 protects against breast cancer liver metastasis by targeting DDR1-mediated immune infiltration.
Topics: Animals; Female; Mice; Ascites; Diterpenes; Liver Neoplasms; Melanoma; Neoplasms, Second Primary; Melanoma, Cutaneous Malignant
PubMed: 37709489
DOI: 10.18632/aging.205030 -
Journal For Immunotherapy of Cancer Aug 2023Ovarian adenocarcinoma (OVAD) frequently metastasizes to the peritoneal cavity and manifests by the formation of ascites, which constitutes a tumor-promoting...
BACKGROUND
Ovarian adenocarcinoma (OVAD) frequently metastasizes to the peritoneal cavity and manifests by the formation of ascites, which constitutes a tumor-promoting microenvironment. In the peritoneal cavity, two developmentally, phenotypically and functionally distinct macrophage subsets, immunocompetent large peritoneal macrophages (LPM) and immunosuppressive small peritoneal macrophages (SPM), coexist. Because peroxisome proliferator-activated receptor γ (PPARγ) is a critical factor participating in macrophage differentiation and cooperates with CCAAT/enhancer binding protein β (C/EBPβ), a transcription factor essential for SPM-to-LPM differentiation, PPARγ could be also involved in the regulation of SPM/LPM balance and could be a promising therapeutic target.
METHODS
To evaluate the 15(S)-hydroxyeicosatetraenoic acid (HETE), a PPARγ endogenous ligand, impact on ovarian tumor growth, we intraperitoneally injected 15(S)-HETE into a murine ovarian cancer model. This experimental model consists in the intraperitoneally injection of ID8 cells expressing luciferase into syngeneic C57BL/6 female mice. This ID8 orthotopic mouse model is a well-established experimental model of end-stage epithelial OVAD. Tumor progression was monitored using an in vivo imaging system. Peritoneal immune cells in ascites were analyzed by flow cytometry and cell sorting. To determine whether the impact of 15(S)-HETE in tumor development is mediated through the macrophages, these cells were depleted by injection of liposomal clodronate. To further dissect how 15(S)-HETE mediated its antitumor effect, we assessed the tumor burden in tumor-bearing mice in which the PPARγ gene was selectively disrupted in myeloid-derived cells and in mice deficient of the recombination-activating gene . Finally, to validate our data in humans, we isolated and treated macrophages from ascites of individuals with OVAD.
RESULTS
Here we show, in the murine experimental model of OVAD, that 15(S)-HETE treatment significantly suppresses the tumor growth, which is associated with the differentiation of SPM into LPM and the LPM residency in the peritoneal cavity. We demonstrate that C/EBPβ and GATA6 play a central role in SPM-to-LPM differentiation and in LPM peritoneal residence through PPARγ activation during OVAD. Moreover, this SPM-to-LPM switch is associated with the increase of the effector/regulatory T-cell ratio. Finally, we report that 15(S)-HETE attenuates immunosuppressive properties of human ovarian tumor-associated macrophages from ascites.
CONCLUSION
Altogether, these results promote PPARγ as a potential therapeutic target to restrain OVAD development and strengthen the use of PPARγ agonists in anticancer therapy.
Topics: Animals; Female; Humans; Mice; Adenocarcinoma; Ascites; Carcinoma, Ovarian Epithelial; Immunosuppression Therapy; Immunosuppressive Agents; Macrophages, Peritoneal; Mice, Inbred C57BL; Ovarian Neoplasms; PPAR gamma; Tumor Microenvironment
PubMed: 37586764
DOI: 10.1136/jitc-2023-007031 -
Pharmacological Research Sep 2023Gastrointestinal cancer remains a significant global health burden. The pursuit of advancing the comprehension of tumorigenesis, along with the identification of... (Review)
Review
Gastrointestinal cancer remains a significant global health burden. The pursuit of advancing the comprehension of tumorigenesis, along with the identification of reliable biomarkers and the development of precise therapeutic strategies, represents imperative objectives in this field. Exosomes, small membranous vesicles released by most cells, commonly carry functional biomolecules, including noncoding RNAs (ncRNAs), which are specifically sorted and encapsulated by exosomes. Exosome-mediated communication involves the release of exosomes from tumor or stromal cells and the uptake by nearby or remote recipient cells. The bioactive cargoes contained within these exosomes exert profound effects on the recipient cells, resulting in significant modifications in the tumor microenvironment (TME) and distinct alterations in gastrointestinal tumor behaviors. Due to the feasibility of isolating exosomes from various bodily fluids, exosomal ncRNAs have shown great potential as liquid biopsy-based indicators for different gastrointestinal cancers, using blood, ascites, saliva, or bile samples. Moreover, exosomes are increasingly recognized as natural delivery vehicles for ncRNA-based therapeutic interventions. In this review, we elucidate the processes of ncRNA-enriched exosome biogenesis and uptake, examine the regulatory and functional roles of exosomal ncRNA-mediated intercellular crosstalk in gastrointestinal TME and tumor behaviors, and explore their potential clinical utility in diagnostics, prognostics, and therapeutics.
Topics: Humans; Exosomes; RNA, Untranslated; Carcinogenesis; Gastrointestinal Neoplasms; Biomarkers; Tumor Microenvironment
PubMed: 37543095
DOI: 10.1016/j.phrs.2023.106880