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Clinical and Translational Medicine Apr 2024IL-17A and TNF synergistically promote inflammation and tumorigenesis. Their interplay and impact on ovarian carcinoma (OC) progression are, however, poorly understood....
BACKGROUND
IL-17A and TNF synergistically promote inflammation and tumorigenesis. Their interplay and impact on ovarian carcinoma (OC) progression are, however, poorly understood. We addressed this question focusing on mesothelial cells, whose interaction with tumor cells is known to play a pivotal role in transcoelomic metastasis formation.
METHODS
Flow-cytometry and immunohistochemistry experiments were employed to identify cellular sources of IL-17A and TNF. Changes in transcriptomes and secretomes were determined by bulk and single cell RNA sequencing as well as affinity proteomics. Functional consequences were investigated by microscopic analyses and tumor cell adhesion assays. Potential clinical implications were assessed by immunohistochemistry and survival analyses.
RESULTS
We identified Th17 cells as the main population of IL-17A- and TNF producers in ascites and detected their accumulation in early omental metastases. Both IL-17A and its receptor subunit IL-17RC were associated with short survival of OC patients, pointing to a role in clinical progression. IL-17A and TNF synergistically induced the reprogramming of mesothelial cells towards a pro-inflammatory mesenchymal phenotype, concomitantly with a loss of tight junctions and an impairment of mesothelial monolayer integrity, thereby promoting cancer cell adhesion. IL-17A and TNF synergistically induced the Th17-promoting cytokines IL-6 and IL-1β as well as the Th17-attracting chemokine CCL20 in mesothelial cells, indicating a reciprocal crosstalk that potentiates the tumor-promoting role of Th17 cells in OC.
CONCLUSIONS
Our findings reveal a novel function for Th17 cells in the OC microenvironment, which entails the IL-17A/TNF-mediated induction of mesothelial-mesenchymal transition, disruption of mesothelial layer integrity and consequently promotion of OC cell adhesion. These effects are potentiated by a positive feedback loop between mesothelial and Th17 cells. Together with the observed clinical associations and accumulation of Th17 cells in omental micrometastases, our observations point to a potential role in early metastases formation and thus to new therapeutic options.
Topics: Humans; Female; Th17 Cells; Interleukin-17; Cytokines; Ovarian Neoplasms; Inflammation; Tumor Microenvironment
PubMed: 38566518
DOI: 10.1002/ctm2.1604 -
MBio May 2024Portal vein tumor thrombosis (PVTT) frequently leads to malignant ascites (MA) in individuals with hepatocellular carcinoma (HCC), remaining a bottleneck in the...
Portal vein tumor thrombosis (PVTT) frequently leads to malignant ascites (MA) in individuals with hepatocellular carcinoma (HCC), remaining a bottleneck in the treatment. This study aimed to explore the differences in microbes in paired groups and provide novel insights into PVTT and MA-related treatments. Formalin-fixed paraffin embedding ascite samples were collected from MA secondary to HCC and benign ascites (BA) secondary to liver cirrhosis (LC). Ascitic microbiota profiles were determined in the HCC and LC groups by 16S rRNA sequencing. Prognostic risk factors were screened using survival analysis. The correlation between the significantly different microbial signatures in the groups with PVTT (WVT) and non-PVTT (NVT) and clinical characteristics was explored. The expression of different immune cells was determined by labeling four markers in the MA tissue chips using multiplex immunohistochemistry. A total of 240 patients (196 with HCC with MA and 44 with LC with BA) were included in this study. Microbial profiles differed between the HCC and LC groups. PVTT and Barcelona Clinic Liver Cancer stage were shown to be prognostic risk factors. Significant differences in the alpha and beta diversities were observed between the WVT and NVT groups. and were the most abundant in the HCC MA. Differences in microbial signatures between the WVT and NVT groups were correlated with the level of C-reactive protein and apolipoprotein A1. This study revealed the microbial differences in the tumor microenvironment of MA secondary to HCC and BA secondary to LC.IMPORTANCEFirst, we explored the alteration of the ascites ecosystem through the microbiota in patients with hepatocellular carcinoma (HCC) and liver cirrhosis. Second, this is the first clinical study to investigate the differences between patients with HCC with and without portal vein tumor thrombosis via 16S rRNA sequencing. These results revealed a decreased microbial diversity and metabolic dysregulation in individuals with HCC and portal vein tumor thrombosis. and were the most abundant in the HCC malignant ascitic fluid. Our study provides a new perspective on treating malignant ascites secondary to HCC.
Topics: Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Male; Female; Portal Vein; Middle Aged; Prognosis; Microbiota; RNA, Ribosomal, 16S; Aged; Ascites; Bacteria; Venous Thrombosis; Liver Cirrhosis; Adult
PubMed: 38564690
DOI: 10.1128/mbio.00245-24 -
The Journal of Clinical Investigation Apr 2024Cancer-derived small extracellular vesicles (sEVs) are capable of modifying the tumor microenvironment and promoting tumor progression. Ovarian cancer (OvCa) is a lethal... (Observational Study)
Observational Study Clinical Trial
Cancer-derived small extracellular vesicles (sEVs) are capable of modifying the tumor microenvironment and promoting tumor progression. Ovarian cancer (OvCa) is a lethal malignancy that preferentially spreads through the abdominal cavity. Thus, the secretion of such vesicles into the peritoneal fluid could be a determinant factor in the dissemination and behavior of this disease. We designed a prospective observational study to assess the impact of peritoneal fluid-derived sEVs (PFD-sEVs) in OvCa clinical outcome. For this purpose, 2 patient cohorts were enrolled: patients with OvCa who underwent a diagnostic or cytoreductive surgery and nononcological patients, who underwent abdominal surgery for benign gynecological conditions and acted as the control group. Systematic extraction of PFD-sEVs from surgical samples enabled us to observe significant quantitative and qualitative differences associated with cancer diagnosis, disease stage, and platinum chemosensitivity. Proteomic profiling of PFD-sEVs led to the identification of molecular pathways and proteins of interest and to the biological validation of S100A4 and STX5. In addition, unsupervised analysis of PFD-sEV proteomic profiles in high-grade serous ovarian carcinomas (HGSOCs) revealed 2 clusters with different outcomes in terms of overall survival. In conclusion, comprehensive characterization of PFD-sEV content provided a prognostic value with potential implications in HGSOC clinical management.
Topics: Humans; Female; Ovarian Neoplasms; Extracellular Vesicles; Ascitic Fluid; Middle Aged; Proteomics; Aged; Prospective Studies; Neoplasm Proteins; Adult
PubMed: 38564289
DOI: 10.1172/JCI176161 -
Indian Journal of Pathology &... Mar 2024Strongyloides stercoralis is a parasitic nematode that infects millions of people worldwide. It primarily infects humans but can also be found in domestic animals and...
Strongyloides stercoralis is a parasitic nematode that infects millions of people worldwide. It primarily infects humans but can also be found in domestic animals and primates. The severity of infection varies from asymptomatic to life-threatening complications. We present a case of a 56-year-old male with a known case of angiosarcoma liver with massive ascites and low-grade fever. He was clinically diagnosed as having malignant ascites and was planned for chemotherapy. During therapeutic cum diagnostic ascitic tap, cell block sections revealed the presence of cross sections of nematode S. stercoralis gravid uterus with eggs. Later, stool for ova and cysts also revealed multiple larval forms of the nematode. S. stercoralis hyperinfection is often accompanied by sepsis or meningitis with enteric organisms. Patient was started on tab. ivermectin 12 mg once a day for two days (in the standard dosage of 200 mcg/kg) was then repeated in the same dosage for another two days after two weeks, and gradually the ascites settled. Post-treatment ascitic tap cell block preparations did not show any parasites. Patient has been on follow-up for 6 months, and he remains asymptomatic.
PubMed: 38563713
DOI: 10.4103/ijpm.ijpm_801_23 -
Journal of Rheumatic Diseases Apr 2024The triad of ascites, pleural effusion, and elevated cancer antigen-125 (CA-125) levels in the absence of ovarian malignancy in systemic lupus erythematosus patients is...
The triad of ascites, pleural effusion, and elevated cancer antigen-125 (CA-125) levels in the absence of ovarian malignancy in systemic lupus erythematosus patients is specifically named pseudo-pseudo Meigs' syndrome (PPMS) or Tjalma syndrome. In this case we reported a 33 years female patient with pleural effusion lasting for 3 years and new onset progressive massive ascites and increased level of CA-125. After she was evaluated for an underlying benign and malign ovarian tumor or any other malignancies, serologic tests were requested with respect to progressive renal dysfunction, proteinuria, lymphopenia, anemia, and effusion. She was diagnosed with systemic lupus erythamatosus (SLE) and renal biopsy showed class-V lupus nephritis. Immunosuppressive treatment led to improvement in both SLE activity and components of PPMS, including massive ascites and pleural effusion and without the need of diuretics. Co-existence of unexplained CA-125 increase, pleural effusion, and ascites might be related to PPMS and detailed examination to exclude malignancy and early and effective treatment of SLE are the mainstay of management.
PubMed: 38559801
DOI: 10.4078/jrd.2023.0052 -
Scientific Reports Mar 2024High grade serous carcinoma (HGSC) metastasises primarily intraperitoneally via cancer spheroids. Podocalyxin (PODXL), an anti-adhesive transmembrane protein, has been...
High grade serous carcinoma (HGSC) metastasises primarily intraperitoneally via cancer spheroids. Podocalyxin (PODXL), an anti-adhesive transmembrane protein, has been reported to promote cancer survival against chemotherapy, however its role in HGSC chemoresistance is unclear. This study investigated whether PODXL plays a role in promoting chemoresistance of HGSC spheroids. We first showed that PODXL was expressed variably in HGSC patient tissues (n = 17) as well as in ovarian cancer cell lines (n = 28) that are more likely categorised as HGSC. We next demonstrated that PODXL-knockout (KO) cells proliferated more slowly, formed less compact spheroids and were more fragile than control cells. Furthermore, when treated with carboplatin and examined for post-treatment recovery, PODXL-KO spheroids showed significantly poorer cell viability, lower number of live cells, and less Ki-67 staining than controls. A similar trend was also observed in ascites-derived primary HGSC cells (n = 6)-spheroids expressing lower PODXL formed looser spheroids, were more vulnerable to fragmentation and more sensitive to carboplatin than spheroids with higher PODXL. Our studies thus suggests that PODXL plays an important role in promoting the formation of compact/hardy HGSC spheroids which are more resilient to chemotherapy drugs; these characteristics may contribute to the chemoresistant nature of HGSC.
Topics: Female; Humans; Carboplatin; Ovarian Neoplasms; Sialoglycoproteins; Carcinoma
PubMed: 38553472
DOI: 10.1038/s41598-024-57053-7 -
International Journal of Women's Health 2024Meigs' syndrome is a rare gynecological disease characterized by the triad of benign ovarian tumor, ascites, and pleural effusion. Ovarian malignancies should be highly...
PURPOSE
Meigs' syndrome is a rare gynecological disease characterized by the triad of benign ovarian tumor, ascites, and pleural effusion. Ovarian malignancies should be highly suspected in a postmenopausal woman with a pelvic mass, ascites, hydrothorax, and an elevated carbohydrate antigen 125 (CA125) level. It can be challenging to make a preoperative diagnosis of Meigs' syndrome. In this report, we present a case of Meigs' syndrome caused by an ovarian fibrothecoma and review the relevant literature to raise awareness and avoid misdiagnosis.
CASE PRESENTATION
An 82-year-old woman with a 2-week history of abdominal distension was admitted to the Department of Gynecology. Ultrasound and thoracoabdominal computed tomography scans showed a left-sided hypoechoic mass in the pelvic cavity with bilateral pleural effusion and massive ascites. The CA125 concentration was 1040 U/mL (normal, 0-35 U/mL). With a working diagnosis of ovarian malignancy, the patient underwent ultrasound-guided fine-needle puncture of the pelvic mass and paracentesis to drain the ascites. The fine-needle puncture and paracentesis fluid analysis results revealed that the ascites did not contain any tumor cells, and the pelvic mass was identified as a spindle cell tumor. Immunohistochemistry confirmed that it was a sex-cord stromal tumor. Total abdominal hysterectomy and bilateral adnexectomy were performed under general anesthesia. The pathology results confirmed the mass to have been an ovarian fibrothecoma. At the 2-month postoperative follow-up, the ascites and hydrothorax had resolved and not recurred, and the CA125 level was normal.
CONCLUSION
Despite the high suspicion of ovarian carcinoma in postmenopausal women presenting with pelvic mass, ascites, pleural effusion, and elevated CA125, Meigs' syndrome should be considered.
PubMed: 38544782
DOI: 10.2147/IJWH.S450833 -
Medicina (Kaunas, Lithuania) Mar 2024Although ovarian cystic teratoma is the most common ovarian tumor, complications are quite rare. However, it is important to be recognized by the radiologist in order to...
Although ovarian cystic teratoma is the most common ovarian tumor, complications are quite rare. However, it is important to be recognized by the radiologist in order to avoid inaccurately diagnosing them as malignant lesions. This case report describes a 61-year-old postmenopausal woman, who presented to the emergency room with abdominal pain following a minor blunt abdominal trauma. In this context, a CT scan was performed, which showed the presence of round, hypodense masses randomly distributed in the peritoneum, with coexisting ascites in moderate amount; ovarian carcinoma with peritoneal carcinomatosis was suspected. The patient was hospitalized and an MRI of the abdomen and pelvis was recommended for a more detailed lesion characterization. Following this examination, the patient was diagnosed with mature cystic ovarian teratoma complicated by rupture. Surgery was performed, and the outcome was favorable. The cases of ruptured cystic teratomas are rare, and to our knowledge, this is the first occurrence described in literature. Special attention must be paid when confronting with such a case in medical practice, since it can easily misdiagnosed as peritoneal carcinomatosis.
Topics: Female; Humans; Middle Aged; Peritoneal Neoplasms; Ovarian Neoplasms; Carcinoma; Teratoma
PubMed: 38541186
DOI: 10.3390/medicina60030460 -
Cancers Mar 2024Malignant Brenner tumors are rare ovarian tumors, accounting for less than 1% of malignant ovarian neoplasms. The aim of this manuscript is to systematically review the... (Review)
Review
BACKGROUND
Malignant Brenner tumors are rare ovarian tumors, accounting for less than 1% of malignant ovarian neoplasms. The aim of this manuscript is to systematically review the current literature concerning malignant Brenner tumors.
METHODS
We searched three medical databases (PubMed, Scopus, and Web of Science) for relevant articles published until 15 September 2023.
RESULTS
After applying inclusion and exclusion criteria, 48 manuscripts describing 115 cases were included in this study from the English literature.
CONCLUSIONS
We analyzed the demographic, clinical, pathological, and oncological characteristics of 115 patients with malignant Brenner tumors. The statistical analysis showed that recurrence was marginally statistically significantly related to tumor stage and was more common in patients with ascites and in women with abnormal CA-125 levels; patients that were treated with lymphadenectomy had better disease-specific survival.
PubMed: 38539441
DOI: 10.3390/cancers16061106 -
Journal of Clinical and Experimental... 2024We report the case of a 52-year-old male who presented to our hospital with cervical lymphadenopathy. Lymph node biopsy revealed small atypical lymphoid cells positive...
We report the case of a 52-year-old male who presented to our hospital with cervical lymphadenopathy. Lymph node biopsy revealed small atypical lymphoid cells positive for CD3 and CD5 and negative for CD56 and Epstein-Barr virus (EBV)-encoded small RNA (EBER) by in situ hybridization. CD4-positive cells and CD8-positive cells were mixed in almost equal numbers. He was diagnosed with peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). The patient received one cycle of chemotherapy, resulting in severe sepsis. While undergoing treatment in the intensive care unit with an antimicrobial agent and prednisone, ascitic fluid appeared. Abdominal aspiration revealed neutrophil-predominant ascites and microbiological studies revealed Candida albicans. However, ascites did not improve when treated with micafungin for Candida peritonitis. Abdominal aspiration was re-performed, and atypical lymphoid cells that were positive for CD3 and CD56 were detected. EBV-DNA levels in whole blood were significantly elevated. Atypical lymphoid cells were positive for EBER by in situ hybridization and Southern blot analysis showed EBV terminal repeat monoclonal patterns. Bone marrow examination revealed the same atypical lymphoid cells. Therefore, the patient was diagnosed with extranodal natural killer/T-cell lymphoma (ENKTL) with bone marrow involvement 3 months after the diagnosis of PTCL-NOS. Complications associated with PTCL-NOS and ENKTL are rare. PTCL-NOS, chemotherapy, sepsis, and prednisone might have led to immunodeficiency and reactivation of EBV, which might be one of the pathophysiologies for developing ENKTL. Our case indicates that measuring EBV-DNA in the blood is a simple and prompt examination to detect complications of EBV-associated lymphoma.
Topics: Male; Humans; Middle Aged; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Lymphoma, T-Cell, Peripheral; Prednisone; Lymphoma, Extranodal NK-T-Cell; Ascites; Killer Cells, Natural; DNA
PubMed: 38538319
DOI: 10.3960/jslrt.23049