Clinical analysis of 21 cases of nongestational ovarian choriocarcinoma.

INTRODUCTION: The objective of the study was to investigate the clinical characters, diagnosis, treatment, and prognosis of nongestational ovarian choriocarcinoma. METHODS: A retrospective analysis was done on 21 patients with nongestational ovarian choriocarcinoma treated in Peking Union Medical College Hospital from January 1985 to October 2008. All patients' conditions were diagnosed by histopathologic examination; in 3 of them, the diagnosis was confirmed by DNA polymorphism analysis at 12 short tandem repeat loci. RESULTS: Correct diagnosis was achieved in only 3 patients before initial treatment. All patients received standard multiple-drug combined chemotherapy and underwent an operation. The mean number of chemotherapy courses for each patient was 10. Of the 21 patients, 16 achieved complete remission, and 4 obtained partial remission; 1 died. In a median follow-up of 71.4 months, the 5-year overall survival rate was 79.4%. CONCLUSIONS: The early diagnosis of nongestational ovarian choriocarcinoma is expected to be improved. DNA polymorphism analysis is a useful tool in determining the origin of ovarian choriocarcinoma. The prognosis is optimistic if managed with standard multiple-drug chemotherapy combined with surgical treatment.

[Genetic genesis of choriocarcinoma].

OBJECTIVE: To distinguish choriocarcinoma from gestational or non-gestational choriocarcinoma and also identify the causative pregnancy of gestational choriocarcinoma by the genetic origin through molecular genetic analysis. METHODS: Twelve patients with choriocarcinoma, who had experienced surgery prior to chemotherapy were enrolled in this study. All 12 cases were diagnosed pathologically as choriocarcinoma. Peripheral venous blood samples and formalin-fixed paraffin-embedded blocks of choriocarcinoma tissue microdissected from haematoxylin and eosin-stained sections of tissue by microdissection method were available from the patient and (or) her husband. DNA was then prepared from the couples' blood samples and choriocarcinoma tissue by using standard techniques. PCR amplification and fluorescent microsatellite genotyping were performed by using DNA from the couples and captured choriocarcinoma tissues. The genetic contributions to the choriocarcinoma tissue were determined by comparing the fragments of genes from the choriocarcinoma tissue to those from blood samples of the couples. RESULTS: The primary lesion was ovary in 7 cases, but only 4 of them had the maternal contribution, indicating a non-gestational origin; the other three were gestational choriocarcinoma. The primary lesion was uterus in 5 cases, which were all gestational choriocarcinoma confirmed by genetic analyses. The causative pregnancies of the 8 cases with gestational choriocarcinoma were identified as androgenetic complete hydatidiform mole (AnCHM) in six cases and normal pregnancies in two cases, respectively. CONCLUSION: Microsatellite polymorphism analysis is a molecular approach for distinguishing the non-gestational choriocarcinoma from the gestational one, and also be used to identify the causative pregnancy of gestational choriocarcinoma.

Prognosis of malignant gestational trophoblastic neoplasia: 20 years of experience.

OBJECTIVE: To analyze retrospectively the management and prognosis of malignant gestational trophoblastic neoplasia (GTN) patients treated at Peking Union Medical College (PUMC) Hospital from 1985 to 2005. STUDY DESIGN: From 1985 to 2005 1,130 GTN patients were treated at PUMC Hospital. Management and prognosis were analyzed retrospectively. The analyses of prognostic factors were performed by using univariate and multivariate analyses. RESULTS: Among the 1,130 patients 903 (80.0%) achieved complete remission (CR), 187 (16.5%) partial remission (PR) and 40 (3.5%) died of progress of the disease (PD). Among the CR patients, 31 (3.4%) relapsed later. Of the 187 PR patients, 155 (82.0%) had normal beta-hCG titer but with residual tumor in the lung or other organs. Among them, 6 patients with choriocarcinoma experienced PD after treatment. One hundred thirty-nine patients became pregnant during follow-up, with a total of 159 pregnancies. Among them, abnormal pregnancy rate was 16.4%, molar rate was 3.1% and fetal abnormality rate was 1.6%. CONCLUSION: Most GTN patients can be cured completely with timely and appropriate chemotherapy treatment. In select cases, surgery should be performed to obtain a better curative outcome. Patients whose residual metastatic tumors remain unchanged after beta-hCG returns to normal are assumed to have CR. We recommend that patients postpone pregnancy for at least 12 months after chemotherapy.

Changes of clinical features in hydatidiform mole: analysis of 113 cases.

OBJECTIVE: To investigate the changes of the clinical features of hydatidiform mole. STUDY DESIGN: A total of 113 cases of hydatidiform mole treated in Peking Union Medical College Hospital during 1989-2006 were reviewed retrospectively, and a comparison was made to historic data from 1948-1975 using the chi2 test. RESULTS: The median age was 28 years (range, 20-55). The median gestational age was 90.2 days. Vaginal bleeding remains the most common presenting symptom, occurring in 94 of 113 cases (83.2%). Of 113 cases, 52 (46%) presented with excessive uterine size. Preeclampsia, hyperemesis, hemoptysis and theca lutein cysts occurred in 4 of 113 (3.5%), 12 of 113 (10.6%), 4 of 113 (3.5%) and 19 of 113 cases (16.8%), respectively. The incidence of postmolar trophoblastic neoplasia was 21% (24 of 113). Compared to historic data, the incidence of vaginal bleeding and preeclampsia were statistically lower (p < 0.005). The incidence of postmolar gestational trophoblastic neoplasia was increased moderately without statistical significance compared to historic data. CONCLUSION: Because of the wide use of ultrasonography and serum human chorionic gonadotropin test, current patients with hydatidiform mole have been diagnosed earlier in gestation and the clinical features have changed. Patterns of medical practice should be changed as well.

[Pulmonary resection in the management of gestational trophoblastic neoplasia: a clinical study].

OBJECTIVE: To investigate the effect of surgical resection in the management of gestational trophoblastic neoplasia (GTN) patients with pulmonary metastases. METHODS: A retrospective review of the medical records of 62 GTN patients who underwent pulmonary resection was carried out. The cases were divided into recurrent group (group A, n = 10), drug-resistant group (group B, n = 28), and the group with satisfactory response to chemotherapy but residual pulmonary lesion (s) (group C, n = 25). One patient underwent lobectomy twice, and she was allocated simultaneously to groups A and B. The patients' median age, antecedent pregnancy, International Federation of Gynecology and Obstetrics (FIGO) risk score, number of preoperative chemotherapy courses, preoperative beta-human chorionic gonadotrophin (beta-hCG) titer, lesion size, number of lobes affected, positive rate of histology, follow-ups and prognosis were compared between the three groups. RESULTS: The proportion of high-risk patients in the three groups was 90%, 82% and 44%, respectively. The complete remission rates of the three groups were 90%, 79% and 100%, with relapse rates of 2/8, 15% and zero, respectively. Positive histology of the resected specimen was more frequently recognized in recurrent and drug-resistant groups (A 60%, B 36%, C 12%). In the drug-resistant group there were more preoperative chemotherapy sessions (A 3, B 7, C 5) and more patients with abnormal preoperative beta-hCG titer (A 50%, B 61%, C 12%). CONCLUSIONS: Surgical resection is effective in the treatment of pulmonary metastases of GTN. Surgery is indicated when clinical evidence suggests that pulmonary metastatic disease causes relapse or drug-resistance and the lesions are relatively localized. Surgical resection is not recommended for patients with satisfactory response to chemotherapy but residual pulmonary lesions.

[Efficacy of surgical management combined with chemotherapy in the treatment of drug-resistant gestational trophoblastic neoplasm].

OBJECTIVE: To evaluate the efficacy of surgical management combined with chemotherapy in the treatment of drug-resistant gestational trophoblastic neoplasm (GTN) patients, and investigate factors influencing the outcome of the surgery combined with chemotherapy. METHODS: Medical records of 42 patents with drug-resistant GTN who were treated by chemotherapy combined with surgical management at Peking Union Medical College Hospital from Jan 1996 to Jan 2006 were reviewed. RESULTS: Among 42 patients, 32 achieved serologically complete remission (SCR) with an SCR rate of 76%, and 10 patients had a treatment failure. Treatment failure was more frequently seen in patients who also had metastasis of other sites except for lungs and vagina and patients with antecedent non-molar pregnancy (P = 0.023 and 0.017, respectively). Preoperative human chorionic gonadotropin-beta subunit (beta-hCG) titer > 10 U/L (P = 0.020), failure to reach normal serum titers of beta-hCG during treatment (P = 0.003), age > or = 35 years (OR: 12.6, 95% CI: 2.4 - 66.0, P = 0.002) and preoperative chemotherapy regimens > or = 4 (OR: 4.5, 95% CI: 1.0 - 20.1, P = 0.059) were also correlated with treatment failure. All the 10 patients with treatment failure had at least 3 of 6 above mentioned predictors of treatment failure. CONCLUSIONS: Surgical management combined with chemotherapy is effective in the treatment of drug-resistant GTN. Age > or = 35 years, antecedent non-molar pregnancy, metastasis of other sites except for lungs and vagina, preoperative beta-hCG titer > 10 U/L, failure to reach normal serum titers of beta-hCG during treatment, and preoperative chemotherapy regimens > or = 4 are significant predictors of treatment failure. Patients with 3 or more predictors of treatment failure usually have poor prognosis. Therefore, surgical management should not be performed for these patients.

[Outcome of gestational trophoblastic neoplasia patients with residual lung tumor after completion of treatment].

OBJECTIVE: To analyze retrospectively the prognosis of gestational trophoblastic neoplasia (GTN) patients who achieved normal human chorionic gonadotropin-beta subunit (beta-hCG) titer after completing treatment but remained with residual lung tumor. METHODS: A total of 1130 GTN patients were hospitalized at Peking Union Medical College Hospital from Jan 1985 to Jan 2004. Among these patients, 901 achieved complete remission (CR); 152 achieved normal blood beta-hCG titer after the completion of treatment but remained with residual lung tumor (defined as partial remission). Retrospective analyses were carried out on the 152 patients. Statistical analysis was used to compare the recurrent rate of the CR patients with the progression rate of the 152 patients. RESULTS: The blood beta-hCG level of all the 152 patients returned to normal after they received 1-30 courses of standard multiple-drug combined chemotherapy treatment. Another 0-8 courses of chemotherapy were applied to these patients before they left hospital. Seventeen of the 152 patients lost to follow-up. Of the rest 135 patients followed up for 14 to 110 months, 83 showed no significant changes in terms of their residual tumors; the residual tumors in 46 patients diminished or disappeared; and the other 6 patients had progression of disease (PD), with beta-hCG levels going up 6-8 months after completing treatment (increased lung metastases were observed in four of the six patients). There was no significant difference (P > 0.05) between the recurrent rate [3.4% (31/901)] of the 901 CR patients and the progression rate [3.9% (6/152)] of the 152 patients. There was also no significant difference (P > 0.05) between the recurrent rate [2.2% (10/463)] of the CR patients with lung metastasis and the progression rate of the 152 patients. CONCLUSIONS: After normalization of beta-hCG titer, patients whose lung tumors remained unchanged even after several additional courses of chemotherapy should be considered as CR patients. Follow-ups should be strictly carried out on these patients, especially at around 6 months after the completion of treatment, and particularly for high-risk and drug-resistant choriocarcinoma patients.

[Value of hysteroscopy and laparoscopy in differential diagnosis of gestational trophoblastic neoplasia].

OBJECTIVE: To determine the efficacy of hysteroscopy and laparoscopy in differential diagnosis of pregnancy-related diseases, including gestational trophoblastic neoplasia (GTN), incomplete abortion and ectopic pregnancy. METHODS: Twenty-seven patients with a suspected diagnosis of GTN were transferred to Peking Union Medical College Hospital from September 2003 to March 2006, and underwent hysteroscopy and laparoscopy. Clinical data of patients were reviewed retrospectively. Most patients had abnormal vaginal bleeding and persistently elevated plasma beta human chorionic gonadotropin (beta-hCG) level for a median (53 +/- 37) days (range, 15 - 125 days) after evacuation. Ultrasound revealed a lesion with affluent blood flow in intrauterine, unilateral horn of uterus, or myometrium. No positive findings were revealed by computerized tomography or X-ray of the chest in all patients. Eleven patients underwent evacuation under hysteroscope, 10 patients were diagnosed and treated by laparoscopy, and 6 by hysteroscopy and laparoscopy. RESULTS: Choriocarcinoma was diagnosed in 4 patients, who achieved complete remission by chemotherapy later. The diagnosis of GTN was ruled out in the other 23 patients, including cornual pregnancy in 12, pregnancy in rudimentary horn in 1, and incomplete abortion in 10, who were cured by hysteroscopic and laparoscopic surgery and postoperative adjuvant single dose methotrexate. CONCLUSIONS: The major causes of pregnancy-related abnormal bleeding include incomplete abortion, ectopic pregnancy, and GTN. Hysteroscopy and laparoscopy are effective alternative of diagnosis for differentiation of GTN from non-GTN and can also offer therapeutic treatment.

Clinical and pathologic characteristics and prognosis of placental site trophoblastic tumor.

OBJECTIVE: To analyze the clinical and pathologic characteristics of placental site trophoblastic tumor (PSTT) cases and to discuss the diagnosis, treatment and prognosis of PSTT. STUDY DESIGN: The clinical and pathologic data on 11 patients with PSTT at Peking Union Medical College Hospital (PUMCH) from 2000 to 2005 were analyzed retrospectively using SPSS 11.0 software (Chicago, Illinois). RESULTS: Between 2000 and 2005, 635 patients with gestational trophoblastic neoplasms were treated at PUMCH, 11 with PSTT (1.73%). The mean age was 36 years. The antecedent pregnancy was molar in 5 cases (45.5%), full-term delivery in 4 cases (36.4%) and missed abortion in 2 cases (18.2%). The mean interval from the antecedent pregnancy to diagnosis was 16 months. The most common presentations were vaginal bleeding (72.7%) and amenorrhea (63.6%). All patients were pathologically diagnosed, in most cases with human placental lactogen immunohistochemical stain. Chemotherapy and hysterectomy were performed on all patients. Nine complete remissions and 1 partial remission were attained after therapy. CONCLUSION: Pathologic diagnosis of PSTT was the gold standard. Multidrug chemotherapy combined with hysterectomy was effective in metastasis cases. (J Re-

[Management and risk factors of recurrent gestational trophoblastic tumor].

OBJECTIVE: To analyze the management, prognosis and prognostic risk factors of recurrent gestational trophoblastic tumor (GTT). METHODS: One thousand one hundred and thirty GTT patients, aged 29 +/- 6, were hospitalized and treated and 901 of them got complete remission (CR). Among these CR patients, 31 suffered relapsed. The clinical data of these 31 cases were analyzed retrospectively. RESULTS: Thirty-one patients suffered 15.3 months (6-72 months) after the cessation of treatment with an overall recurrence rate of 3.4% (31/901). Four of the 31 patients suffered relapse repeatedly (totally seven times), resulting in an overall re-recurrence rate of 22.6% (7/31). Twenty-five of the 31 patients were re-hospitalized and received treatment. Eighteen of them got complete remission (CR), 3 got partial remission (PR), and 4 died of progress of the disease (PD). The major adverse prognostic risk factors included: clinical stage (P < 0.05), an interval of more than 12 months from the antecedent pregnancy to chemotherapy (OR = 3.170, P < 0.05), declination of beta-hCG level back to normal titer after more than seven courses of chemotherapy (OR = 4.775, P < 0.05), and less than two courses of consolidation chemotherapy (OR = 0.441, P < 0.05). CONCLUSION: More attention should be given to those GTT patients with adverse prognostic risk factors. Multi-drug and multiple route chemotherapy and/or combined surgical intervention can be used to improve the cure rate and lower the re-recurrence rate of the GTT recurrent patients.

[Management and prognosis in stage IV gestational trophoblastic neoplasia patients].

OBJECTIVE: To analyze the management and prognosis in stage IV gestational trophoblastic neoplasia (GTN) patients. METHODS: One thousand one hundred and thirty GTN patients were hospitalized and treated at Peking Union Medical College Hospital from year 1985 to 2004. Ninety-two of them were diagnosed as stage IV of GTN. Retrospective analyses were carried out on these patients in terms of management and prognosis. RESULTS: Of the 92 patients who had undergone treatment, complete remission (CR) was achieved in 33, partial remission in 37, and progress of the disease was seen in 22. Among all the CR patients, three had recurrence later. Thirty-three out of all the patients died during or after treatment. Among the 92 cases, 70 had one or two metastases, of whom 27 had CR, and 20 died. Of the 17 cases who had three metastases, 5 achieved CR, and 10 died. Of the five cases with >or= 4 metastases, one had CR, and three died. The number of metastatic organs was correlated with prognosis (P = 0.034) and death (P = 0.018). CONCLUSIONS: Multi-drug and multi-route chemotherapy and (or) combined surgical intervention may improve the survival rate of the stage IV GTN patients. The management should be individualized for different patients with metastases. With the increase in the number of metastatic organs, the remission rate decreases.

[Factors related to recurrence of choriocarcinoma and evaluation of treatment outcomes].

OBJECTIVE: To analyse the factors associated with recurrence of choriocarcinoma and to evaluate the treatment outcomes of choriocarcinoma. METHODS: The records of 490 patients with choriocarcinoma treated at Peking Union Medical College Hospital (PUMCH) were reviewed and evaluated for recurrent episodes of choriocarcinoma. RESULTS: Three hundred and ninety-four women achieved primary remission; 17 (4.3%) developed one or more episodes of recurrent choriocarcinoma. Recurrent rate in low-risk patients was 2.4% (5/208), while in high-risk patients 6.5% (12/186). Recurrent rates among those without and with 1 course of maintenance chemotherapy patients were 6.1% (3/49) and 9.8% (6/61) respectively, while in 2, 3, and >3 courses of maintenance therapy patients were 1.4% (1/70), 3.9% (2/51) and 3.1% (5/163) respectively. Thirteen (76.5%, 13/17) patients with recurrent choriocarcinoma recurred within 3 years and 4 patients after 3 years. Sixteen (94.1%) of 17 patients achieved secondary remission; 6 (37.5%) of 16 developed a second recurrence, and one was lost to follow-up after partial remission. In addition, 21 patients were referred to PUMCH from other hospitals for salvage therapy at the time of recurrence. Totally 38 patients of recurrent choriocarcinoma were treated at our hospital; 29 recurred once, 7 recurred twice and 2 recurred 4 times. There were totally 51 instances treated for recurrent choriocarcinoma. The complete remission rates in patients using chemotherapy only was 69.2% (18/26), the second recurrent rates of these patients was 50.0% (9/18); the complete remission rates in patients using chemotherapy combined with surgery was 92.0% (23/25), the second recurrent rates of these patients was 17.4% (4/23). CONCLUSIONS: Factors related to development of recurrent choriocarcinoma include high-risk at initial evaluation and less than two courses of maintenance chemotherapy beyond the primary remission. Most patients of recurrent choriocarcinoma recur within 3 years; the recurrent choriocarcinoma is of poor prognosis and should be treated aggressively. Chemotherapy combined with surgery is the most important method to increase cure rates and to decrease recurrent rates.

[Efficacy of FAEV regimen in treatment of high-risk drug-resistant gestational trophoblastic tumor].

OBJECTIVE: To evaluate the efficacy of floxuridine, actinomycin D, etoposide, vincristine (FAEV) regimen in treatment of high-risk drug-resistant gestational trophoblastic tumor (GTT). METHODS: From October 2001 to May 2004, 11 cases of high-risk drug-resistant GTT were treated with FAEV regimen. The International Federation of Gynecology and Obstetrics (FIGO) prognosis score (2000) was 7 to 13 (median 9). All patients were referred to Peking Union Medical College Hospital because of failure of chemotherapy previously. After the FAEV treatment, they were followed up for 15 to 42 months. RESULTS: Seven cases (64%, 7/11) were cured by FAEV regimen. The median treatment course for serum human chorionic gonadotropin reaching normal level was 3. Four cases (36%, 4/11) showed drug-resistant to FAEV regimen. The major side effect of FAEV regimen was myelosuppression. Granulocyte colony stimulating factor support was needed after 98% (63/64) of the courses. CONCLUSION: For those high-risk drug-resistant GTT cases, FAEV regimen could be considered as an effective choice of treatment.

[Analysis of death causes of gestational trophoblastic neoplasia patients].

OBJECTIVE: To analyze retrospectively the causes of death in gestational trophoblastic neoplasia (GTN) patients. The prognostic risk factors were also discussed. METHODS: One thousand one hundred and thirty GTN patients were hospitalized and treated at Peking Union Medical College Hospital from 1985 to 2004. Sixty-four of them died later and retrospective analyses were carried out on these patients. RESULTS: Fifty-eight out of the 64 patients died during initial treatment. The other six died from disease relapse and progression of the disease (PD). The major causes of death were multi-organ failure, intracranial haemorrhage, cerebral herniation, side-effects of chemotherapy, and PD after relapse. The result of multivariate analysis indicated the adverse prognostic factors included the interval between antecedent pregnancy and chemotherapy treatment (OR = 2.857, P < 0.01), the titer of beta subunit of human chorionic gonadotropin (beta-hCG, P < 0.05), the diagnosis of choriocarcinoma (OR = 3.635, P < 0.05), clinical stage (P < 0.05), multiple metastases (OR = 2.201, P < 0.01) and drug resistance (OR = 0.181, P < 0.01). CONCLUSIONS: A proper evaluation of a GTN patient before initial treatment is important. More attention should be paid to the death-related prognostic risk factors to improve the prognosis of high risk GTN patients.

[Clinical characters and prognosis of postpartum choriocarcinoma].

OBJECTIVE: To analyze the clinical characters and prognosis of postpartum choriocarcinoma. METHODS: Retrospective analysis of 103 patients diagnosed with postpartum choriocarcinoma in Peking Union Medical College Hospital between 1985 and 2005 was performed. RESULTS: In a total of 103 cases of postpartum choriocarcinoma treated with multiagent cytotoxic chemotherapy and combined modality therapy, 92 patients (89.3%) achieved a complete remission while 2 patients had a partial remission, and 9 patients died. Regarding 25 cases with chemorefractory choriocarcinoma and 4 relapsed cases, 18 and 3 cases achieved a complete remission respectively. According to the new International Federation of Gynecology and Obstetrics (FIGO) 2000 staging and risk factor scoring system, 17 cases were at FIGO stage I, 8 cases at stage II, 56 cases at stage III, and 22 cases at stage IV. Complete remission was achieved in 100%, 8/8, 95% and 64% respectively. Thirty-five cases in low risk group had FIGO scores < or = 6, and all achieved a complete remission. Of 68 cases in high risk group with FIGO scores > or = 7, 57 (84%) of them obtained a complete remission. There were significant differences in the two groups (P < 0.05). CONCLUSION: Postpartum choriocarcinoma could have an increasing probability of cure with early diagnosis and the use of modern multiagent cytotoxic chemotherapy and combined modality therapy.

[Clinical characteristics and genetic analyses of familial recurrent moles].

OBJECTIVE: To probe the clinical characteristics and genetic origin of familial recurrent mole (FRM). METHODS: Two cases of FRM were reported retrospectively. Microsatellite polymorphism was used to determine the genetic origin of the two FRM and other six sporadic moles from other independent families. RESULTS: The two FRM patients came from two independent families. Both of them had more than two times of hydatidiform moles and the same condition had happened to their sisters. The last mole from each of these two patients was identified as biparental complete hydatidiform mole (BiCHM). Among the six sporadic moles, one was partial hydatidiform mole (PHM), which was identified as triploid with one haploid maternal set of chromosomes and two haploid paternal sets of chromosomes. The other five sporadic moles were all androgenetic complete hydatidiform mole (AnCHM), which lacked maternal genetic material. The two women with FRM developed into persistent trophoblastic disease (PTD) and gained complete remission (CR) after medical therapy and/or pulmonary lobectomy. CONCLUSIONS: FRM is exceedingly rare. Most of them are biparental in origin. It ought to be an important step to identify the genetic origin in evaluating the outcomes of the women with recurrent hydatidiform moles.

PGC-1α regulates the cell cycle through ATP and ROS in CH1 cells.

Peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) is a transcriptional co-activator involved in mitochondrial biogenesis, respiratory capacity, and oxidative phosphorylation (OXPHOS). PGC-1α plays an important role in cellular metabolism and is associated with tumorigenesis, suggesting an involvement in cell cycle progression. However, the underlying mechanisms mediating its involvement in these processes remain unclear. To elucidate the signaling pathways involved in PGC-1α function, we established a cell line, CH1 PGC-1α, which stably overexpresses PGC-1α. Using this cell line, we found that over-expression of PGC-1α stimulated extra adenosine triphosphate (ATP) and reduced reactive oxygen species (ROS) production. These effects were accompanied by up-regulation of the cell cycle checkpoint regulators CyclinD1 and CyclinB1. We hypothesized that ATP and ROS function as cellular signals to regulate cyclins and control cell cycle progression. Indeed, we found that reduction of ATP levels down-regulated CyclinD1 but not CyclinB1, whereas elevation of ROS levels down-regulated CyclinB1 but not CyclinD1. Furthermore, both low ATP levels and elevated ROS levels inhibited cell growth, but PGC-1α was maintained at a constant level. Together, these results demonstrate that PGC-1α regulates cell cycle progression through modulation of CyclinD1 and CyclinB1 by ATP and ROS. These findings suggest that PGC-1α potentially coordinates energy metabolism together with the cell cycle.

Improving P-gp expression in human mononuclear cells in vitro transfected by multidrug resistance-1 mRNA.

OBJECTIVE: To evaluate the expression and function activity of P-glycoprotein (P-gp) in human mononuclear cells (MNCs) in vitro transfected by multidrug resistance-1 (MDR1) mRNA. METHODS: Two MDR1 cDNA vectors, pT7TS_MDR1 and pGEM5Zf(+)_MDR1, were constructed and transcripted in vitro. Vector pGEM5Zf(+)_MDR1 only contained the coding region of mdr1 cDNA, and pT7TS_MDR1 also included Xeponus beta-globin 5' and 3' untranslated region. MNCs were prepared from peripheral blood of parvicellular lung cancer patient. The two human mdrl mRNAs were then transferred into human MNCs in vitro by DOTAP. And the expression efficiency and pump function of P-gp were measured with flow cytometry. RESULTS: Expression of P-gp significantly elevated in both transferred cells compared with untransferred cells (P < 0.01). And pT7TS_MDR1 showed higher capability in elevating the expression of P-gp than pGEM5Zf(+)_MDR1 (P < 0.01). The P-gp function was elevated in both pT7TS_MDR1 and pGEM5Zf(+) MDR1 groups. The survival ratio of MNCs in erythrocyte-lysis-solution (ELS, 86.07%) and lymphocyte-isolation-solution (LIS, 83.67%) had no significant difference. The CD34+ cells content of the MNCs used for transfection was 2.65% and 1.01% in ELS and LIS group, respectively (P < 0.01). CONCLUSIONS: It is a feasible approach to improve P-gp expression in human MNCs by transfection of MDR-1 mRNA. And the ELS may be more suitable for purifing MNCs for mRNA transfection than LIS.

[Etopside, methotrexate, kengshengmycin/etopside, cisplatin chemotherapy for chemorefractory gestational trophoblastic tumour].

OBJECTIVE: To evaluate the results of etopside, methotrexate, kengshengmycin/etopside, cisplatin (EMA/EP) chemotherapy in patients with chemorefractory gestational trophoblastic tumour. METHODS: Fifteen patients with chemorefractory gestational trophoblastic tumour were treated by EMA/EP chemotherapy schedule. RESULTS: Twelve of the fifteen cases were choriocarcinoma, and the other three were metastatic placental site trophoblastic tumour (PSTT). International Federation of Gynecology and Obstetrics (FIGO), 2 cases stage I, 10 cases stage III, 3 cases stage IV. Eight cases had FIGO score of 7 to 12, the score of the other 7 cases was over 12. Fifteen patients received a total of 93 cycles of the study regimen. The median number of courses for each patient was 6.2. Eleven cases (73%) achieved a complete remission while 3 patients (20%) had a partial remission, 1 case (7%) showed nonresponse. The main complications for EMA/EP chemotherapy were myelosuppression and gastrointestinal symptoms. CONCLUSIONS: The EMA/EP regimen is an effective treatment for chemorefractory gestational trophoblastic tumour, and the chemotherapeutic results can be further improved while combined with surgery and arterial infusion chemotherapy in the selected patients. Meanwhile, EMA/EP regimen should be considered in the primary management of patients with metastatic PSTT.

[Clinical characteristics and management of gestational trophoblastic disease in women aged 50 years or more].

OBJECTIVE: To investigate the clinical characteristics, management and prognosis of gestational trophoblastic disease in women aged 50 years or more. METHODS: Thirty-eight cases of gestational trophoblastic disease in women aged 50 years or more, who were treated in Peking Union Medical College Hospital between 1992 and 2002, were reviewed retrospectively. RESULTS: The median age was 52 years (range from 50 to 58 years). The lesions included 5 hydatidiform moles (13%), 19 invasive moles (50%), 12 choriocarcinomas (32%) and 2 placenta site trophoblastic tumors (5%). All of 38 cases presented with abnormal vaginal bleeding. Twenty-three cases of hydatidiform moles were diagnosed at their first visit to the hospital, and 15 of them received prophylactic chemotherapy, of whom 10 progressed to invasive mole, 3 developed lung metastasis. All of the other 8 cases without prophylactic chemotherapy progressed to malignant changes with metastasis of lung. The use of prophylactic chemotherapy reduced the incidence of subsequent metastasis. All of 38 cases received chemotherapy. Thirty-two cases underwent hysterectomy, complete remission was achieved in 91% of patients; complete remission was achieved in 2 of 6 patients without hysterectomy. CONCLUSIONS: The diagnosis of pregnancy and pregnancy-related disease should be considered in the elderly women presenting with abnormal vaginal bleeding. Once gestational trophoblastic disease in women aged 50 years or more is diagnosed, chemotherapy should be given as soon as possible. Hysterectomy is frequently required to improve the prognosis of gestational trophoblastic disease in the elderly women.