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BMJ Case Reports Feb 2011A 32-year-old lady presented postnatally with headaches, blurred vision and left leg numbness, which was initially diagnosed as migraine with sciatica. Subsequently, she...
A 32-year-old lady presented postnatally with headaches, blurred vision and left leg numbness, which was initially diagnosed as migraine with sciatica. Subsequently, she developed seizures and was admitted to ITU. Investigations revealed abnormal grey matter perfusion in the right occipital region of the brain, multiple lung nodules, lesions in the liver and a pancreatic mass. A β-human chorionic gonadotrophin level was over 132,000 IU/l, and metastatic choriocarcinoma was diagnosed. She responded well to combination chemotherapy and made a full recovery.
Topics: Adult; Choriocarcinoma; Female; Humans; Puerperal Disorders; Uterine Neoplasms
PubMed: 22714612
DOI: 10.1136/bcr.09.2010.3320 -
The Lancet. Gastroenterology &... Sep 2017Liver fluke infections occur in people worldwide. In some low-income regions, a combination of ecological, agricultural, and culinary factors leads to a very high... (Review)
Review
Liver fluke infections occur in people worldwide. In some low-income regions, a combination of ecological, agricultural, and culinary factors leads to a very high prevalence of infection but, in higher-income regions, infections are uncommon. Infection is associated with substantial morbidity and several liver fluke species are recognised as biological carcinogens. Here, we review the epidemiology, clinical significance, and diagnostic and treatment strategies of human infection with these pathogens.
Topics: Animals; Anthelmintics; Choriocarcinoma; Endemic Diseases; Fascioliasis; Humans; Liver Neoplasms; Poverty; Prevalence
PubMed: 28786389
DOI: 10.1016/S2468-1253(17)30111-5 -
Revista Espanola de Enfermedades... Mar 2020Choriocarcinomas are epitelial tumors with a rapidly growing rate and widely metastatic tumor of trophoblastic cells. Incidence have been reported 1 in 24,096 pregnant...
Choriocarcinomas are epitelial tumors with a rapidly growing rate and widely metastatic tumor of trophoblastic cells. Incidence have been reported 1 in 24,096 pregnant patients. Most cases arise in the uterus following gestational events. It can also be gonadal or extragonadal. primary gastric choriocarcinoma is rare, represents 0.08% of all gastric cancers. Clinical presentation is very similar to adenocarcinomas but they can present seric β-GCH elevation. The main objective is present three cases of primary gastric choriocarcinoma with an initial miss diagnosis of adenocarcimoa.
Topics: Adenocarcinoma; Choriocarcinoma; Female; Humans; Male; Neoplasms, Germ Cell and Embryonal; Pregnancy; Stomach Neoplasms; Trophoblasts
PubMed: 32022576
DOI: 10.17235/reed.2020.6478/2019 -
Cells Mar 2023Gestational choriocarcinoma (GC) is a highly malignant trophoblastic tumor that often develops from a complete hydatidiform mole (HM). is the major gene responsible for...
BACKGROUND
Gestational choriocarcinoma (GC) is a highly malignant trophoblastic tumor that often develops from a complete hydatidiform mole (HM). is the major gene responsible for recurrent HM and is involved in the innate immune response, inflammation and apoptosis. NLRP7 can function in an inflammasome-dependent or -independent pathway. Recently, we have demonstrated that is highly expressed in GC tumor cells and contributes to their tumorigenesis. However, the underlying mechanisms are still unknown. Here, we investigated the mechanism by which NLRP7 controls these processes in malignant (JEG-3) and non-tumor (HTR8/SVneo) trophoblastic cells. Cell survival, dedifferentiation, camouflage, and aggressiveness were compared between normal JEG-3 cells or knockdown for JEG-3 Sh . In addition, HTR8/SVneo cells overexpressing were used to determine the impact of overexpression on non-tumor cells. NLRP7 involvement in tumor cell growth and tolerance was further characterized in vivo using the metastatic mouse model of GC.
RESULTS
We demonstrate that NLRP7 (i) functions in an inflammasome-dependent and -independent manners in HTR8/SVneo and JEG-3 cells, respectively; (ii) differentially regulates the activity of NF-κB in tumor and non-tumor cells; (iii) increases malignant cell survival, dedifferentiation, and camouflage; and (iv) facilitates tumor cells colonization of the lungs in the preclinical model of GC.
CONCLUSIONS
This study demonstrates for the first time the mechanism by which NLRP7, independently of its inflammasome machinery, contributes to GC growth and tumorigenesis. The clinical relevance of NLRP7 in this rare cancer highlights its potential therapeutic promise as a molecular target to treat resistant GC patients.
Topics: Animals; Female; Humans; Mice; Pregnancy; Adaptor Proteins, Signal Transducing; Carcinogenesis; Cell Line, Tumor; Cell Survival; Choriocarcinoma; Inflammasomes; Neoplasm Recurrence, Local
PubMed: 36980199
DOI: 10.3390/cells12060857 -
Archives of Pathology & Laboratory... Jan 2019Gestational trophoblastic tumors include 3 distinct entities: gestational choriocarcinoma, placental site trophoblastic tumor, and epithelioid trophoblastic tumor.... (Review)
Review
CONTEXT.—
Gestational trophoblastic tumors include 3 distinct entities: gestational choriocarcinoma, placental site trophoblastic tumor, and epithelioid trophoblastic tumor. Accurate diagnosis is important for clinical management of the patient.
OBJECTIVE.—
To review clinical features and pathologic diagnosis of gestational trophoblastic tumors.
DATA SOURCES.—
Literature and personal experience are the sources for this study.
CONCLUSIONS.—
Trophoblastic tumors are rare encounters in modern medicine, as a result of clinical practice of molar surveillance programs and early chemotherapeutic intervention for persistent gestational trophoblastic neoplasia. Diagnostic recognition of these tumors requires a high index of suspicion, awareness of their histologic characteristics, and appropriate application of immunohistochemical and molecular biomarkers. Recent attention has been given to a few precursor lesions of gestational trophoblastic tumors, including early/in situ choriocarcinoma and atypical placental site nodule.
Topics: Choriocarcinoma; Female; Gestational Trophoblastic Disease; Humans; Placenta; Pregnancy; Trophoblastic Tumor, Placental Site; Uterine Neoplasms
PubMed: 30407075
DOI: 10.5858/arpa.2018-0234-RA -
World Journal of Surgical Oncology Jun 2022Gestational choriocarcinoma is a rare trophoblastic tumor that spreads mainly to the lung, liver, and central nervous system. Fewer than 5% of patients present with... (Review)
Review
BACKGROUND
Gestational choriocarcinoma is a rare trophoblastic tumor that spreads mainly to the lung, liver, and central nervous system. Fewer than 5% of patients present with metastasis to the gastrointestinal system and have a poor prognosis CASE PRESENTATION: We describe four cases of patients with intestinal metastasis from choriocarcinoma who visited the First Affiliated Hospital of Zhejiang University School of Medicine and the First People's Hospital of Hangzhou between April 2012 and October 2019. Four patients presented with gastrointestinal symptoms or developed gastrointestinal symptoms during treatment for choriocarcinoma. Three patients had these intestinal lesions surgically removed, and the postoperative pathology results suggested choriocarcinoma. All patients received multiple chemotherapy regimens during treatment for suboptimal human chorionic gonadotropin (hCG) levels; one patient died 22 months after a definitive diagnosis was made, and the other three patients are still undergoing regular follow-up.
CONCLUSION
Given the low incidence of intestinal metastases from choriocarcinoma, the metastatic route of intestinal metastases from choriocarcinoma remains to be elucidated, and diagnosis mainly depends on pathology findings. An effective treatment has not been determined, and surgical excision with chemotherapy is generally accepted.
Topics: Choriocarcinoma; Female; Humans; Pregnancy
PubMed: 35650620
DOI: 10.1186/s12957-022-02623-0 -
BioMed Research International 2022The E3 ubiquitin ligase LRSAM1 (LRSAM1) was involved in many cancers, but whether it exerts anti- or protumor efficacies on choriocarcinoma cellular structures remains...
OBJECTIVE
The E3 ubiquitin ligase LRSAM1 (LRSAM1) was involved in many cancers, but whether it exerts anti- or protumor efficacies on choriocarcinoma cellular structures remains unknown. We wanted to explore the efficacies of aberrant LRSAM1 expression on human choriocarcinoma cellular structures and the underlying mechanisms.
METHODS
LRSAM1 mRNA expressions in choriocarcinoma lines of cells JEG-3 and JAR cellular structures, as well as HTR8/sev8 human trophoblastic cell line cellular structures, were assessed using assay analysis of quantitative real-time polymerase chain reactions. We compared cell proliferation, migratory flow, invasive force, adhesion, and apoptotic process between cellular structures infected with si-LRSAM1 plasmids versus negative controls using CCK-8, clone formation, Transwell, adhesion, and flow cytometry assays. Protein expressions of LRSAM1, E-cadherin, and N-cadherin (indicators of epithelial-mesenchymal transformation) and p53/p21 pathway components were quantitated using a Western blot assay. The morphology of tumor lesions was observed in xenografted nude mice using immunohistochemistry (IHC) analyses.
RESULTS
LRSAM1 was markedly overexpressed within JEG-3 and JAR choriocarcinoma cellular structures compared to HTR8/sev8 trophoblast cellular structures. Compared to si-NC, LRSAM1 knockdown robustly restricted cell proliferating, migratory flow, invasive force, and adhesion and fueled apoptotic cell process in JEG-3 as well as JAR cellular structures and suppressed tumor growth, as evidenced by the reduction in tumor volume and weight in naked mice inoculated with transfected cellular structures. Compared to si-negative control (si-NC), si-LRSAM1 significantly decreased Ki67 (a proliferating indicator) and N-cadherin expressions but reduced E-cadherin expression in JEG-3 and JAR cellular structures. Blocking the p53/p21 pathway by pifithrin-a (a p53 restrictor) successfully reversed the anti-inhibitory effect of LRSAM1 depletion, resulting in enhanced proliferating and metastasis in JEG-3 and JAR cellular structures.
CONCLUSION
LRSAM1 exerts tumorigenic roles in choriocarcinoma. Via the activating of the p53/p21 pathway of signaling and impediment of choriocarcinoma cell proliferating, migratory flow, and invasive force, LRSAM1 knockdown slows the course of the disease. For choriocarcinoma diagnosis and treatment, it serves as a new therapeutic target.
Topics: Animals; Cadherins; Cell Line, Tumor; Choriocarcinoma; Female; Humans; Mice; Mice, Nude; Pregnancy; Tumor Suppressor Protein p53; Ubiquitin-Protein Ligases
PubMed: 36093406
DOI: 10.1155/2022/1926605 -
The Journal of Maternal-fetal &... Dec 2023Intraplacental choriocarcinoma is a gestational trophoblastic neoplasia located within the placenta. Due to the usual silent presentation, more than half of the cases... (Review)
Review
INTRODUCTION
Intraplacental choriocarcinoma is a gestational trophoblastic neoplasia located within the placenta. Due to the usual silent presentation, more than half of the cases are diagnosed incidentally. It has been demonstrated that this pathology is linked to feto-maternal hemorrhage (FMH), stillbirth, and intrauterine growth restriction. The aim of our review was to establish if there are recurrent signs that might lead to an early diagnosis and better management in cases complicated by FMH.
MATERIALS AND METHODS
We performed a systematic review of the literature from 2000 up to March 2023. The adopted research strategy included the following terms: (gestational choriocarcinoma obstetrics outcome) AND (intraplacental choriocarcinoma) AND (gestational choriocarcinoma). The MEDLINE (PubMed), Google Scholar, and Scopus databases were searched.
RESULTS
The research strategy identified 19 cases of FMH coexisting with intraplacental choriocarcinoma (IC), as described in 17 studies. The perinatal mortality rate was 36.8%. In eight cases, histological diagnosis of IC was made post-delivery. Metastatic lesions were found in 75% (6/8) of described cases. One case of maternal death has been described. Chemotherapy was necessary in seven cases. Sporadical prenatal ultrasound signs were described.
DISCUSSION
The diagnosis of IC is usually delayed, mostly due to aspecific symptoms and signs. Histological analysis of the placenta, when not routinely performed, should be performed when warning symptoms are encountered. The maternal prognosis was good, with a mortality rate of 5.5%. A fertility-sparing approach is always possible even in the presence of metastasis. Chemotherapy seems to be useful in cases of maternal and neonatal metastasis.
Topics: Pregnancy; Female; Infant, Newborn; Humans; Fetomaternal Transfusion; Placenta; Choriocarcinoma; Placenta Diseases; Prenatal Care
PubMed: 38010764
DOI: 10.1080/14767058.2023.2285238 -
The International Journal of... Mar 1993Externalization of the visceral yolk sac, after fetectomy, induces the development of extra-embryonal fetal tumors in rodents. These tumors are either benign teratomas... (Review)
Review
Externalization of the visceral yolk sac, after fetectomy, induces the development of extra-embryonal fetal tumors in rodents. These tumors are either benign teratomas that appear 3 to 4 weeks after the displacement of the yolk sac or malignant tumors, i.e. yolk sac carcinomas. The latter appear 4 to 8 months after the surgery. If however, Mouse Sarcoma Virus (MSV) is injected in the placentas at the time of fetectomy (day 12 of pregnancy) the malignant tumors develop much earlier (2 to 3 months after surgery) and some display characteristics of embryonal carcinoma. Whether virus induced or not, the yolk sac carcinomas that develop from the displaced visceral yolk sac possess the same morphological and biological characteristics. They are composed of both parietal and visceral yolk sac structures and sometimes trophoblast. The tumors metastasize, grow in ascites form and kill their host. They are readily transplantable in syngeneic rats and grow in tissue culture as an epithelial-like sheet of cells. On the other hand, the benign teratomas are composed of various well differentiated adult tissues. In these tissues, derivatives of all three germ layers are observed. Numerous experiments prove that the stem cells for these various adult tissues are not germ cells. Instead the stem cells are multipotential cells that arise in the displaced yolk sac by a process of dedifferentiation. These poorly differentiated cells originate from the endoderm of the displaced visceral yolk sac. By redifferentiation they give rise to the various adult tissues characteristic for benign teratomas. The multipotential poorly differentiated cells are also likely to be the target cells for malignant transformation. Malignant transformation of these cells, whether induced by a virus or spontaneously occurring in the displaced yolk sac, leads not only to the development of yolk sac carcinomas and eventually embryonal carcinoma but also, although rarely, to choriocarcinoma. The latter tumor is transplantable in allogeneic hosts. It is hormonally active since it secretes lactogen and progesterone. The extra-embryonal fetal tumors and in particular the rat yolk sac carcinomas and choriocarcinoma proved to be a good source for the detection of oncofetal antigens. At least two different oncofetal endodermal antigens were detected with monoclonal antibodies (mab) made after immunization with yolk sac carcinoma. Another mab, made against choriocarcinoma, was found to react specifically with the cytotrophoblast both in the normal placenta and in the tumor. No other placental cells showed a positive reaction.
Topics: Animals; Antigens, Neoplasm; Cell Differentiation; Choriocarcinoma; Dysgerminoma; Female; Immunohistochemistry; Mice; Rats; Sarcoma Viruses, Murine; Teratoma; Tumor Cells, Cultured
PubMed: 8389575
DOI: No ID Found -
Oncogene Apr 2022Low-risk gestational trophoblastic neoplasia including choriocarcinoma is often effectively treated with Methotrexate (MTX) as a first line therapy. However, MTX...
Low-risk gestational trophoblastic neoplasia including choriocarcinoma is often effectively treated with Methotrexate (MTX) as a first line therapy. However, MTX resistance (MTX-R) occurs in at least ≈33% of cases. This can sometimes be salvaged with actinomycin-D but often requires more toxic combination chemotherapy. Moreover, additional therapy may be needed and, for high-risk patients, 5% still die from the multidrug-resistant disease. Consequently, new treatments that are less toxic and could reverse MTX-R are needed. Here, we compared the proteome/phosphoproteome of MTX-resistant and sensitive choriocarcinoma cells using quantitative mass-spectrometry to identify therapeutically actionable molecular changes associated with MTX-R. Bioinformatics analysis of the proteomic data identified cell cycle and DNA damage repair as major pathways associated with MTX-R. MTX-R choriocarcinoma cells undergo cell cycle delay in G1 phase that enables them to repair DNA damage more efficiently through non-homologous end joining in an ATR-dependent manner. Increased expression of cyclin-dependent kinase 4 (CDK4) and loss of p16 in resistant cells suggested that CDK4 inhibition may be a strategy to treat MTX-R choriocarcinoma. Indeed, inhibition of CDK4/6 using genetic silencing or the clinically relevant inhibitor, Palbociclib, induced growth inhibition both in vitro and in an orthotopic in vivo mouse model. Finally, targeting the ATR pathway, genetically or pharmacologically, re-sensitised resistant cells to MTX in vitro and potently prevented the growth of MTX-R tumours in vivo. In short, we identified two novel therapeutic strategies to tackle MTX-R choriocarcinoma that could rapidly be translated into the clinic.
Topics: Animals; Ataxia Telangiectasia Mutated Proteins; Choriocarcinoma; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase 6; Dactinomycin; Female; Humans; Methotrexate; Mice; Pregnancy; Proteomics
PubMed: 35301407
DOI: 10.1038/s41388-022-02251-8