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Advances in Experimental Medicine and... 2024Mitochondrial dysfunctions are significantly implicated in cancer initiation, progression, and metastasis, which have been shown for several cancers including ovarian... (Review)
Review
Mitochondrial dysfunctions are significantly implicated in cancer initiation, progression, and metastasis, which have been shown for several cancers including ovarian cancer.An increase in mitochondrial dysfunction is also associated with drug resistance along with cancer progression, which in part is related to its specific microenvironment that is characterized by ascites, low glucose levels, and hypoxia that causes ovarian cancer cells to switch to mitochondrial respiration to enable their survival. Peritoneal ascitic fluid accumulation is a specific feature of ovarian cancer, and it is a major cause of its metastatic spread that also presents challenges for effective treatment. Among the treatment difficulties for ovarian cancer is the mutation rate and frequency of mtDNA in ovarian cancer tissue that can affect the efficiency of chemotherapeutic drugs. The varied and multiple mutations of different types enable metabolic reprogramming, cancer cell proliferation, and drug resistance.New specific information on mechanisms underlying several of the mitochondrial dysfunctions has led to proposing various mitochondrial determinants as targets for ovarian cancer therapy, which include targeting specific mitochondrial proteins and phosphoproteins as well as reactive oxygen species (ROS) that accumulate abnormally in cancer cells. Because of the genetically and histologically heterogeneous nature of the disease, combination therapy approaches will be necessary to combat the disease and achieve progress in effective treatment of ovarian cancer. This chapter will address (1) mitochondrial vulnerabilities underlying dysfunction and disease; (2) mitochondrial dysfunction in ovarian cancer; (3) present treatment difficulties for ovarian cancer and new potential treatment strategies to target ovarian cancer mitochondrial metabolism; and (4) biobehavioral factors influencing ovarian cancer development.
Topics: Humans; Ovarian Neoplasms; Female; Mitochondria; Cell Proliferation; Reactive Oxygen Species; Neoplasm Metastasis; Tumor Microenvironment; Animals; DNA, Mitochondrial; Drug Resistance, Neoplasm
PubMed: 38805128
DOI: 10.1007/978-3-031-58311-7_7 -
Clinical & Translational Immunology 2024Recent studies have identified expression of the non-functional P2X7 (nfP2X7) receptor on various malignant cells including ovarian cancer, but not on normal cells,...
OBJECTIVES
Recent studies have identified expression of the non-functional P2X7 (nfP2X7) receptor on various malignant cells including ovarian cancer, but not on normal cells, which makes it a promising tumour-associated antigen candidate for chimeric antigen receptor (CAR)-T-cell immunotherapies. In this study, we assessed the cytotoxic effects of nfP2X7-CAR-T cells on ovarian cancer using and models.
METHODS
We evaluated the effects of nfP2X7-CAR-T cells on ovarian cancer cell lines (SKOV-3, OVCAR3, OVCAR5), normal peritoneal cells (LP-9) and primary serous ovarian cancer cells derived from patient ascites using monolayer and 3D spheroid assays. We also evaluated the effects of nfP2X7-CAR-T cells on patient-derived tissue explants, which recapitulate an intact tumour microenvironment. In addition, we investigated the effect of nfP2X7-CAR-T cells using the OVCAR-3 xenograft model in NOD-scid IL2Rγnull (NSG) mice.
RESULTS
Our study found that nfP2X7-CAR-T cells were cytotoxic and significantly inhibited survival of OVCAR3, OVCAR5 and primary serous ovarian cancer cells compared with un-transduced CD3 T cells . However, no significant effects of nfP2X7-CAR-T cells were observed for SKOV3 or normal peritoneal cells (LP-9) cells with low P2X7 receptor expression. Treatment with nfP2X7-CAR-T cells increased apoptosis compared with un-transduced T cells in patient-derived explants and correlated with CD3 positivity. Treatment with nfP2X7-CAR-T cells significantly reduced OVCAR3 tumour burden in mice compared with un-transduced CD3 cells for 7-8 weeks.
CONCLUSION
This study demonstrates that nfP2X7-CAR-T cells have great potential to be developed as a novel immunotherapy for ovarian cancer.
PubMed: 38800555
DOI: 10.1002/cti2.1512 -
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 -
Journal of Vascular and Interventional... Jun 2024To investigate the safety and effectiveness of intranodal lymphangiography (INL) and lymphatic embolization (LE) in management of chylous ascites after oncologic surgery.
PURPOSE
To investigate the safety and effectiveness of intranodal lymphangiography (INL) and lymphatic embolization (LE) in management of chylous ascites after oncologic surgery.
MATERIALS AND METHODS
Retrospective review of records of patients who underwent INL with or without LE from January 2017 to June 2022 was performed. Adult patients with chylous ascites after oncologic surgery referred to interventional radiology after failure of conservative treatment were included. Thirty-nine patients who underwent 55 procedures were included (34 males and 5 females). Data on patient demographics, procedural technique, outcomes, and follow-up were collected. Descriptive statistics were used to illustrate technical success, clinical success, and adverse events. Univariate logistic regression analysis was performed to evaluate factors predicting clinical success.
RESULTS
INL was technically successful in 54 of 55 procedures (98%; 95% confidence interval [CI], 90%-100%). A lymphatic leak was identified in 40 procedures, and LE was attempted in 36. LE was technically successful in 33 of the 36 procedures (92%; 95% CI, 78%-98%). Clinical success, defined as resolution of ascites with no need for peritoneovenous shunt placement or additional surgery, was achieved in 22 of 39 patients (56%; 95% CI, 40%-72%). Clinical success was achieved in 18 patients after 1 procedure, and patients who required repeat procedures were less likely to achieve clinical success (odds ratio, 0.16; 95% CI, 0.04-0.66; P = .012). Four grade 1 procedural adverse events were recorded.
CONCLUSIONS
INL with or without LE is a safe minimally invasive tool that can help patients with chylous ascites after oncologic surgery who failed conservative treatment avoid more invasive interventions.
Topics: Humans; Chylous Ascites; Male; Female; Lymphography; Retrospective Studies; Embolization, Therapeutic; Middle Aged; Aged; Treatment Outcome; Iatrogenic Disease; Adult; Predictive Value of Tests; Neoplasms; Risk Factors; Radiography, Interventional; Aged, 80 and over; Time Factors
PubMed: 38789205
DOI: 10.1016/j.jvir.2024.02.015 -
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