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Cell Death & Disease May 2024Advanced epithelial ovarian cancer (EOC) survival rates are dishearteningly low, with ~25% surviving beyond 5 years. Evidence suggests that cancer stem cells contribute...
Advanced epithelial ovarian cancer (EOC) survival rates are dishearteningly low, with ~25% surviving beyond 5 years. Evidence suggests that cancer stem cells contribute to acquired chemoresistance and tumor recurrence. Here, we show that IRAK1 is upregulated in EOC tissues, and enhanced expression correlates with poorer overall survival. Moreover, low molecular weight hyaluronic acid, which is abundant in malignant ascites from patients with advanced EOC, induced IRAK1 phosphorylation leading to STAT3 activation and enhanced spheroid formation. Knockdown of IRAK1 impaired tumor growth in peritoneal disease models, and impaired HA-induced spheroid growth and STAT3 phosphorylation. Finally, we determined that TCS2210, a known inducer of neuronal differentiation in mesenchymal stem cells, is a selective inhibitor of IRAK1. TCS2210 significantly inhibited EOC growth in vitro and in vivo both as monotherapy, and in combination with cisplatin. Collectively, these data demonstrate IRAK1 as a druggable target for EOC.
Topics: Interleukin-1 Receptor-Associated Kinases; Humans; STAT3 Transcription Factor; Female; Carcinoma, Ovarian Epithelial; Hyaluronic Acid; Animals; Ovarian Neoplasms; Neoplastic Stem Cells; Cell Line, Tumor; Mice; Cisplatin; Mice, Nude; Phosphorylation; Cell Proliferation; Molecular Weight; Xenograft Model Antitumor Assays
PubMed: 38796478
DOI: 10.1038/s41419-024-06717-3 -
International Journal of Molecular... May 2024Primary cancer cells reflect the genetic background and phenotype of a tumor. Immortalized cells with higher proliferation activity have an advantage over primary cells.... (Comparative Study)
Comparative Study
Primary cancer cells reflect the genetic background and phenotype of a tumor. Immortalized cells with higher proliferation activity have an advantage over primary cells. The aim of the study was to immortalize the primary ovarian cancer (OvCa) cells using the plasmid-carrying human telomerase reverse transcriptase (hTERT) gene and compare their phenotype and biological activity with the primary cells. The primary OvCa3 A and OvCa7 A cells were isolated from the ascitic fluid of two high-grade serous ovarian cancer patients and were characterized using immunocytochemical methods, flow cytometry, real-time RT-PCR, Western blot, metabolic activity, and migratory potential. Both immortalized ovarian cancer cell lines mirrored the phenotype of primary cancer cells, albeit with modifications. The OvCa3 A hTERT cells kept the mesenchymal stem cell phenotype of CD73/CD90/CD105-positivity and were CD133-negative, whereas the cell population of OvCa7 A hTERT lost CD73 expression, but almost 90% of cells expressed the CD133 characteristic for the CSCs phenotype. Immortalized OvCa cells differed in gene expression level with respect to and , which was associated with stemness properties. The OvCa7 A hTERT cells showed higher metabolic and migratory activity and ALDH1 expression than the corresponding primary OvCa cells. Both primary and immortalized cell lines were able to form spheroids. The newly established unique immortalized cell line OvCa7 A hTERT, with the characteristic of a serous ovarian cancer malignancy feature, and with the accumulation of the p53, Pax8, and overexpression of the CD133 and CD44 molecules, may be a useful tool for research on therapeutic approaches, especially those targeting CSCs in ovarian cancer and in preclinical 2D and 3D models.
Topics: Humans; Female; Ovarian Neoplasms; Telomerase; Cell Line, Tumor; Neoplastic Stem Cells; Cell Movement; Gene Expression Regulation, Neoplastic
PubMed: 38791431
DOI: 10.3390/ijms25105384 -
JPMA. the Journal of the Pakistan... May 2024Psuedomyxoma peritonei is an infrequent clinical entity characterised by intraperitoneal mucinous/gelatinous ascites produced by the cancerous cells. It has been...
Psuedomyxoma peritonei is an infrequent clinical entity characterised by intraperitoneal mucinous/gelatinous ascites produced by the cancerous cells. It has been associated with gastrointestinal, gynaecological, lung and breast tumours. It is commonly asymptomatic and is most often detected incidentally on abdominopelvic imaging or laparoscopy. Higher histological grade of the tumour shows increased metabolic activity on 18F-Fluorodeoxyglucose (FDG) positron-emission tomography (PET) computed tomography (CT). It has been rarely reported in patients with sarcoma. We hereby present an interesting case of incidentally diagnosed pseudomyxoma peritonei on 18FDG PET-CT scan of a patient with soft tissue sarcoma of peripheral nerve sheath.
Topics: Humans; Male; Middle Aged; Fluorodeoxyglucose F18; Incidental Findings; Nerve Sheath Neoplasms; Peritoneal Neoplasms; Positron Emission Tomography Computed Tomography; Pseudomyxoma Peritonei; Radiopharmaceuticals
PubMed: 38783460
DOI: 10.47391/JPMA.24-40 -
Journal of Cytology 2024The "International System of Reporting Serous Fluid Cytology (TIS)" together with cytomorphology promotes the use of ancillary techniques to resolve difficulties in...
BACKGROUND
The "International System of Reporting Serous Fluid Cytology (TIS)" together with cytomorphology promotes the use of ancillary techniques to resolve difficulties in reporting serous fluid cytology.
OBJECTIVE
To classify serous effusion fluid samples received at our department in line with "TIS", indicating the risk of malignancy (ROM), and directing appropriate usage of ancillary testing.
MATERIALS AND METHODS
Prospective study carried out from October 2021 to September 2022. The study included all pleural, ascitic, and pericardial fluid samples, reported according to 'TIS'. Flow cytometry and immunocytochemistry were ancillary methods utilized to assist in reporting. Cases with available history and convincing correlations didn't require further assessment.
RESULTS
A total of 1200 serous effusion samples were evaluated including 604 pleural, 591 ascitic, and 5 pericardial fluid samples. After categorization, there were 23 samples in non-diagnostic (ND, 1.9%), 575 in negative for malignancy (NFM, 47.91%), 44 in atypia of undetermined significance (AUS, 3.66%), 64 in suspicious for malignancy (SFM, 5.33%), and 494 in malignant category (MAL, 41.16%). Ancillary studies were beneficial in the recategorization of 26% (11/44) AUS cases, 29.6% (19/64) SFM cases, and it helped refine tumor characteristics in 35.42% (175/494) cases categorized as malignant. Final ROM calculated for each category: ND 25%, NFM 18.6%, AUS 66.6%, SFM 88%, and MAL 100%.
CONCLUSION
Serous fluid is an easily obtainable sample that can provide opportunities for ancillary testing with clinical implications. In AUS and suspicious category although, diagnostic yield is increased however, a larger number of cases are required to obtain definite results.
PubMed: 38779601
DOI: 10.4103/joc.joc_114_23 -
Journal of Nippon Medical School =... 2024The incidence of alcoholic liver cirrhosis (ALC) is increasing. However, few reports have focused on ALC-derived esophageal varices (EV). We retrospectively examined...
BACKGROUND
The incidence of alcoholic liver cirrhosis (ALC) is increasing. However, few reports have focused on ALC-derived esophageal varices (EV). We retrospectively examined differences in overall survival (OS) and EV recurrence rate in patients after endoscopic injection sclerotherapy (EIS) for ALC and hepatic B/C virus liver cirrhosis (B/C-LC).
METHODS
We analyzed data from 215 patients (B/C-LC, 147; ALC, 68) who underwent EIS. The primary endpoints were OS and EV recurrence in patients with unsuccessful abstinence ALC and those with uncontrolled B/C-LC, before and after propensity score matching (PSM) to unify the patients' background. The secondary endpoints were predictors associated with these factors, as determined by multivariate analysis.
RESULTS
The observation period was 1,430 ± 1,363 days. In the analysis of all patients, OS was significantly higher in the ALC group than in the B/C-LC group (p = 0.039); however, there was no difference in EV recurrence rate (p = 0.502). Ascites and history of hepatocellular carcinoma (HCC) (p = 0.019 and p < 0.001, respectively) predicted OS, whereas age and EV size predicted recurrence (p = 0.011 and 0.024, respectively). In total, 96 patients without an HCC history were matched by PSM, and there was no significant difference in OS or EV recurrence rate (p = 0.508 and 0.246, respectively).
CONCLUSION
When limited to patients without a history of HCC, OS and the EV recurrence rate were comparable in patients with ALC who continued to consume alcohol and those with B/C-LC without viral control.
Topics: Humans; Esophageal and Gastric Varices; Male; Female; Recurrence; Middle Aged; Retrospective Studies; Sclerotherapy; Liver Cirrhosis, Alcoholic; Liver Cirrhosis; Treatment Outcome; Aged; Carcinoma, Hepatocellular; Liver Neoplasms; Adult; Propensity Score
PubMed: 38777781
DOI: 10.1272/jnms.JNMS.2024_91-209 -
Journal of Medical Case Reports May 2024Early diagnosis of prostate cancer is key to achieving a cure and its proper management leads to a good prognosis. In Ghana a large percentage of patients present with...
BACKGROUND
Early diagnosis of prostate cancer is key to achieving a cure and its proper management leads to a good prognosis. In Ghana a large percentage of patients present with advanced disease and unusual presentations in these patients result in greater delay in the diagnosis thus worsening the outcomes.
CASE PRESENTATION
We present three African males with advanced prostate cancer who had delayed diagnosis. The first patient, a 64 year old male presented with ascites of 2 years duration with weight loss and no lower urinary tract symptoms, the second, a 69 year old man with end stage renal failure of 6 months duration and was receiving dialysis, the third case, an 87 year old man was managed for pulmonary tuberculosis after he presented with chronic cough and lower urinary tract symptoms. All patients eventually had a prostate specific antigen done which were elevated. Further investigations including prostate biopsies, abdominopelvic CT scans for case 1, abdominopelvic ultrasound, prostate biopsies and blood urea and electrolytes for case 2, prostate biopsies, chest and lumbosacral showed a diagnosis of metastatic prostate carcinoma, and all patients were managed with androgen deprivation. The second patient received additional radiotherapy.
CONCLUSION
A lack of knowledge of prostate cancer symptoms including unusual symptoms, can result in delayed diagnosis especially in regions of the world where a large number of patients present with advanced disease.
Topics: Humans; Male; Prostatic Neoplasms; Delayed Diagnosis; Middle Aged; Aged; Aged, 80 and over; Prostate-Specific Antigen; Ascites; Kidney Failure, Chronic; Ghana
PubMed: 38773554
DOI: 10.1186/s13256-024-04543-x -
BMC Women's Health May 2024Concomitant invasive ovarian mucinous adenocarcinoma, unilateral renal agenesis and bicornuate uterus is a rare combination. Unilateral renal agenesis has been...
BACKGROUND
Concomitant invasive ovarian mucinous adenocarcinoma, unilateral renal agenesis and bicornuate uterus is a rare combination. Unilateral renal agenesis has been associated with genital anomalies, such as unicornuate and bicornuate uterus. Furthermore, a wealth of studies has reported the association between unicornuate uterus and ovarian anomalies, such as the absence of an ovary or ectopic ovaries, but rarely has there been a combination of the three to the best of our knowledge. The present case report is the first case presentation with a combination of the three syndromes: ovarian mucinous tumor, unilateral renal agenesis, and bicornuate uterus.
CASE PRESENTATION
We report the case of a 17-year-old who presented with abdominal distension. On examination, a CT scan revealed a large multicystic abdominal mass on the right side, with an absence of the right kidney while the left kidney was normal in size, appearance, and position. Intraoperatively, massive blood-stained ascitic fluid was evacuated. Additionally, a large whitish polycystic intra-abdominal mass with mucus-like materials and solid areas was attached to the midpoint of the colon and the right ovary, with visible metastasis to the omentum. The uterus was bicornuate. The mass and omentum were taken for histopathology and a diagnosis of invasive ovarian mucinous cystadenocarcinoma with metastasis to the colon and omentum was made after a pathological report.
CONCLUSIONS
The presence of these conditions in the same individual could potentially complicate medical management and fertility considerations. Thus, a need for a multidisciplinary medical team, including gynecologists, urologists, and oncologists, to address their unique needs and provide appropriate treatment and guidance. Further research and case studies are needed to better understand the possible association and implications of these rare co-occurring conditions.
Topics: Adolescent; Female; Humans; Adenocarcinoma, Mucinous; Bicornuate Uterus; Congenital Abnormalities; Kidney; Ovarian Neoplasms; Solitary Kidney; Tomography, X-Ray Computed; Uterus
PubMed: 38769573
DOI: 10.1186/s12905-024-03130-y -
Zoological Research May 2024Hepatocellular carcinoma (HCC), a prevalent solid carcinoma of significant concern, is an aggressive and often fatal disease with increasing global incidence rates and...
Hepatocellular carcinoma (HCC), a prevalent solid carcinoma of significant concern, is an aggressive and often fatal disease with increasing global incidence rates and poor therapeutic outcomes. The etiology and pathological progression of non-alcoholic steatohepatitis (NASH)-related HCC is multifactorial and multistage. However, no single animal model can accurately mimic the full NASH-related HCC pathological progression, posing considerable challenges to transition and mechanistic studies. Herein, a novel conditional inducible wild-type human overexpressed mouse model (HRAS-HCC) was established, demonstrating 100% morbidity and mortality within approximately one month under normal dietary and lifestyle conditions. Advanced symptoms of HCC such as ascites, thrombus, internal hemorrhage, jaundice, and lung metastasis were successfully replicated in mice. In-depth pathological features of NASH- related HCC were demonstrated by pathological staining, biochemical analyses, and typical marker gene detections. Combined murine anti-PD-1 and sorafenib treatment effectively prolonged mouse survival, further confirming the accuracy and reliability of the model. Based on protein-protein interaction (PPI) network and RNA sequencing analyses, we speculated that overexpression of HRAS may initiate the THBS1-COL4A3 axis to induce NASH with severe fibrosis, with subsequent progression to HCC. Collectively, our study successfully duplicated natural sequential progression in a single murine model over a very short period, providing an accurate and reliable preclinical tool for therapeutic evaluations targeting the NASH to HCC continuum.
Topics: Animals; Non-alcoholic Fatty Liver Disease; Carcinoma, Hepatocellular; Mice; Liver Neoplasms; Proto-Oncogene Proteins p21(ras); Disease Models, Animal; Mice, Transgenic; Mice, Inbred C57BL; Humans
PubMed: 38757223
DOI: 10.24272/j.issn.2095-8137.2024.002 -
Frontiers in Immunology 2024[This corrects the article DOI: 10.3389/fimmu.2024.1360615.].
[This corrects the article DOI: 10.3389/fimmu.2024.1360615.].
PubMed: 38742114
DOI: 10.3389/fimmu.2024.1420991 -
Oncoimmunology 2024Immune exhaustion is a hallmark of ovarian cancer. Using multiparametric flow cytometry, the study aimed to analyze protein expression of novel immunological targets on...
Immune exhaustion is a hallmark of ovarian cancer. Using multiparametric flow cytometry, the study aimed to analyze protein expression of novel immunological targets on CD3 T cells isolated from the peripheral blood ( = 20), malignant ascites ( = 16), and tumor tissue ( = 6) of patients with ovarian cancer (OVCA). The study revealed an increased proportion of effector memory CD8 T cells in OVCA tissue and malignant ascites. An OVCA-characteristic PD-1 CD8 T cell population was detected, which differed from PD-1CD8 T cells by increased co-expression of TIGIT, CD39, and HLA-DR. In addition, these OVCA-characteristic CD8 T cells showed reduced expression of the transcription factor TCF-1, which may also indicate reduced effector function and memory formation. On the contrary, the transcription factor TOX, which significantly regulates terminal T cell-exhaustion, was found more frequently in these cells. Further protein and gene analysis showed that CD39 and CD73 were also expressed on OVCA tumor cells isolated from solid tumors ( = 14) and malignant ascites ( = 9). In the latter compartment, CD39 and CD73 were also associated with the expression of the "don't eat me" molecule CD24 on tumor cells. Additionally, ascites-derived CD24EpCAM tumor cells showed a higher frequency of CD39 or CD73 cells. Furthermore, CD39 expression was associated with unfavorable clinical parameters. Expression of CD39 on T cells was upregulated through CD3/CD28 stimulation and its blockade by a newly developed nanobody construct resulted in increased proliferation (eFluor), activation (CD25 and CD134), and production of cytotoxic cytokines (IFN-γ, TNF-α, and granzyme-B) of CD8 T cells.
Topics: Humans; Female; Ovarian Neoplasms; Apyrase; CD8-Positive T-Lymphocytes; Middle Aged; Ascites; Antigens, CD; Aged; Programmed Cell Death 1 Receptor; Receptors, Immunologic; T Cell Transcription Factor 1; HLA-DR Antigens; Adult; T-Cell Exhaustion; High Mobility Group Proteins
PubMed: 38737794
DOI: 10.1080/2162402X.2024.2346359