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Fulltext Term delivery of a complete hydatidiform mole with a coexisting living fetus followed by successful treatment of maternal metastatic gestational trophoblastic disease

Peng HH, Huang KG, Chueh HY, Adlan AS, Chang SD, Lee CL

Taiwan J Obstet Gynecol, 2014 Sep;53(3):397-400.
PMID: 25286799 DOI: 10.1016/j.tjog.2013.02.005

OBJECTIVE: A twin pregnancy consisting of a complete hydatidiform mole with a coexisting normal fetus is extremely rare with an incidence of 1/22,000 to 1/100,000. The incidence of preterm delivery is high and few pregnancies reach near term with a viable fetus.
CASE REPORT: A 34-year-old woman presented at 20 weeks of gestation with increased levels of serum beta human chorionic gonadotropin (beta-HCG) at 4.74 multiples of the median (310277.7 mIU/mL). Ultrasonography showed a hydatidiform mole together with a normal fetus. Fetal karyotyping revealed 46XY. The serum beta-HCG levels were followed up throughout the remainder of the pregnancy. A male infant weighting 2260 g and the molar tissue were delivered at 37 weeks of gestation. The karyotype of the molar tissue showed 46XX and the histopathological report confirmed our diagnosis. At 4 months postpartum, metastatic gestational trophoblastic disease of the lung was diagnosed in the mother by a computed tomography scan due to increased beta-HCG levels. The patient received three unsuccessful cycles of methotrexate and folinate. Another four cycles of chemotherapy consisting of etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine (EMA-CO) were initiated and the beta-HCG levels returned to normal. There was no evidence of recurrence in the subsequent 5 years of regular follow up.
CONCLUSION: A pregnancy with a complete hydatidiform mole and a living cotwin can be a serious threat to the health of both the mother and the fetus. Early diagnosis depends on a combination of detecting an unusually high level of serum beta-HCG and ultrasound examination. We suggest that continuation of the pregnancy may be an acceptable option and that the pregnancy may continue until term if a normal fetal anatomy is assured and maternal complications are under control. Patients require careful postpartum follow up and any recurrent disease should be managed aggressively.
KEYWORDS: EMA-CO; metastatic gestational trophoblastic disease; twin pregnancy with one complete hydatidiform mole

Matched MeSH terms: Uterine Neoplasms/drug therapy
Fulltext Anti-Uterine Fibroid Effect of Standardized Labisia Pumila Var. Alata Extracts In Vitro and in Human Uterine Fibroid Cancer Xenograft Model

Zakaria N, Mohd KS, Ahmed Saeed MA, Ahmed Hassan LE, Shafaei A, Al-Suede FSR, et al.

Asian Pac J Cancer Prev, 2020 Apr 01;21(4):943-951.
PMID: 32334454 DOI: 10.31557/APJCP.2020.21.4.943

BACKGROUND: Uterine fibroids are a common type of solid tumor presenting in women of reproductive age. There are very few alternative treatment available from conventional treatment involving surgeries. Labisia pumila var. alata or locally known as 'Kacip Fatimah' was widely used as traditional medicine in Malaysia. This plant has been used to maintain a healthy female reproductive system. The present study aimed to evaluate anti fibroid potential of L. pumila extracts through in vitro apoptosis activity against uterine leiomyoma cells (SK-UT-1) and in uterine leiomyoma xenograft model. Evaluation of bioactive markers content were also carried out.
METHODS: Apoptotic induction of the extracts was determined by morphological examination of AO/PI dual staining assay by flourescent microscopy and flow cytometry analysis on Annexin V-FITC/PI stained cells. In vivo study was done in immune-compromised mouse xenograft model. HPLC analysis was employed to quantify marker compounds.
RESULTS: Morphological analysis showed L. pumila induced apoptosis in a dose dependent manner against SK-UT-1 cells. In vivo study indicated that L. pumila significantly suppressed the growth of uterine fibroid tumor. All tested extracts contain bioactive marker of gallic acid and cafeic acid.
CONCLUSION: This work provide significant data of the potential of L. pumila in management of uterine fibroids.
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Matched MeSH terms: Uterine Neoplasms/drug therapy*
FZD1 activates protein kinase C delta-mediated drug-resistance in multidrug-resistant MES-SA/Dx5 cancer cells

Hung TH, Chen CM, Tseng CP, Shen CJ, Wang HL, Choo KB, et al.

Int J Biochem Cell Biol, 2014 Aug;53:55-65.
PMID: 24814288 DOI: 10.1016/j.biocel.2014.04.011

Multidrug-resistant (MDR) cancer is a major clinical problem in chemotherapy of cancer patients. We have noted inappropriate PKCδ hypomethylation and overexpression of genes in the PKCδ/AP-1 pathway in the human uterus sarcoma drug-resistant cell line, MES-SA/Dx5 cells, which also overexpress p-glycoprotein (ABCB1). Recent studies have indicated that FZD1 is overexpressed in both multidrug-resistant cancer cell lines and in clinical tumor samples. These data have led us to hypothesize that the FZD1-mediated PKCδ signal-transduction pathway may play an important role in drug resistance in MES-SA/Dx5 cells. In this work, the PKCδ inhibitor Rottlerin was found to reduce ABCB1 expression and to inhibit the MDR drug pumping ability in the MES-SA/Dx5 cells when compared with the doxorubicin-sensitive parental cell line, MES-SA. PKCδ was up-regulated with concurrent up-regulation of the mRNA levels of the AP-1-related factors, c-JUN and c-FOS. Activation of AP-1 also correlated with up-regulation of the AP-1 downstream genes HGF and EGR1. Furthermore, AP-1 activities were reduced and the AP-1 downstream genes were down-regulated in Rottlerin-treated or PKCδ shRNA-transfected cells. MES-SA/Dx5 cells were resensitized to doxorubicin-induced toxicity by co-treatment with doxorubicin and Rottlerin or PKCδ shRNA. In addition, cell viability and drug pump-out ability were significantly reduced in the FZD1 inhibitor curcumin-treated and FZD1 shRNA-knockdown MES-SA/Dx5 cells, indicating involvement of PKCδ in FZD1-modulated ABCB1 expression pathway. Taken together, our data demonstrate that FZD1 regulates PKCδ, and the PKCδ/AP-1 signalling transduction pathway plays an important role in drug resistance in MES-SA/Dx5 cells.

Matched MeSH terms: Uterine Neoplasms/drug therapy
A case report: metastatic choriocarcinoma to the gum

Shafiee MN, Ismail NM, Shan LP, Kampan N, Omar MH, Dali HM

Sex Reprod Healthc, 2011 Apr;2(2):91-2.
PMID: 21439527 DOI: 10.1016/j.srhc.2011.02.001

Choriocarcinoma is a rare neoplasia with a tendency of distant metastasis although highly sensitive to chemotherapy renders a good prognosis and outcome. Lungs, liver and cerebral metastasis are commonly implicated with maxillofacial region rarely involved. We illustrate a case of overwhelming metastatic choriocarcinoma to lungs, liver, brain and to the extreme of gum metastasis. Decompressive craniectomy for intracranial bleeding, multiple transfusions to correct anaemia and coagulopathy were done before high-risk-regime chemotherapy. Despite this, due to fulminant multi-organs involvement she finally succumbed to death. In conclusion, gum bleeding in choriocarcinoma may suggest metastasis and poor prognosis.

Matched MeSH terms: Uterine Neoplasms/drug therapy
Cerebral metastases from choriocarcinoma. Results of chemotherapy

Sen DK, Sivanesaratnam V, Chuah CY, Ch'ng SL, Singh J, Paramsothy M

Acta Obstet Gynecol Scand, 1987;66(5):425-8.
PMID: 3425244

Of 36 cases of choriocarcinoma treated at the University Hospital Kuala Lumpur during 1980-84 inclusive, 6 patients were found to have cerebral metastases. Intrathecal methotrexate and combination chemotherapy were started in all cases, with monitoring of tumor growth by serial beta-HCG assays and CT scanning of brain and lung. Chemotherapy was reduced because of severe toxicity in 2 patients, one of whom received radiotherapy to the brain. Four patients (66%) have now been in remission for 2.5-6 years. Two did not respond to therapy and died. The factors involved in therapy and response are discussed.

Matched MeSH terms: Uterine Neoplasms/drug therapy*
All-trans retinoic acid (atra) inhibits telomerase expression of BeWo choriocarcinoma cell (ATCC CCL-98)

Tatit NS, Kevin P

Med J Malaysia, 2019 12;74(6):504-508.
PMID: 31929476

INTRODUCTION: Choriocarcinoma is malignant cancer originating from placental trophoblast. The incidence of this cancer is estimated at 0.57-1.1 per 1000 births in the United States of America, Australia, Europe, and New Zealand. The rate is much higher in South East Asia and Japan with two occurrences per a thousand births. Telomerase activity is an important part of the apoptotic process. Increased telomerase activity will result in cellular immortality and poor prognosis in cancer. Vitamin A possess an essential role in cell proliferation and differentiation. One of the active metabolites of vitamin A is All-Trans Retinoic Acid (ATRA).
METHODS: In this study, we examined the role of ATRA against telomerase activity in choriocarcinoma cell. This cell was derived from BeWo cell line (ATCC CCL-98) and were given different doses of ATRA.
RESULTS: From this study, Choriocarcinoma cell that was given ATRA in dosage of 50μg/ml inhibit telomerase activity by extending the cycle time of 39.51±0.09, compared to the control group with a cycle time of 37.62±0.43. Cycle length change consistently with higher dose of ATRA.
CONCLUSION: This study has proven that ATRA could inhibit telomerase activity by lengthening the cycle. Changes in the increase of ATRA doses in this experimental test need to be studied further on experimental animals, either administered as a single agent or as an addition to standard treatment of trophoblastic disease.

Matched MeSH terms: Uterine Neoplasms/drug therapy*
Orthosiphon stamineus Extracts Inhibits Proliferation and Induces Apoptosis in Uterine Fibroid Cells

Pauzi N, Mohd KS, Abdul Halim NH, Ismail Z

Asian Pac J Cancer Prev, 2018 Oct 26;19(10):2737-2744.
PMID: 30360599

Objectives: The effects of water and 50% ethanolic-water extracts of Orthosiphon stamineus Benth (OS) on cell proliferation and apoptotic activity against uterine leiomyosarcoma (SK-UT-1) cells were investigated. Methods: Anti-proliferation effect was evaluated through cell cycle analysis whereas apoptotic activity was determined via screening and quantifying using fluorescence microscopy and flow cytometric analysis, respectively. The effect of extracts on molecular mechanism was studied using real-time reverse transcription polymerase chain reaction and Western blotting. Results: Cell cycle flow cytometric analysis showed the induction of cell cycle arrests were behaves in a p53-independent manner. The examination using fluorescence microscopy and Annexin V flow cytometry revealed the presence of morphological features of apoptotic bodies. Downregulation of anti-apoptotic gene (Bcl-2) supports the apoptotic activity of OS extracts although poorly induce PARP-1 cleavage in Western blot analysis. The extracts also inhibit the SK-UT-1 growth by suppressing VEGF-A, TGF-β1 and PCNA genes, which involved in angiogenesis and cell proliferation. Conclusion: This study demonstrates that O. stamineus extracts are able to inhibit proliferation and induced apoptosis of uterine fibroid cells and is worth further investigation.

Matched MeSH terms: Uterine Neoplasms/drug therapy