Effectiveness of third-line chemotherapy in recurrent ovarian cancer patients.

OBJECTIVE: Despite recent advances in the treatment of recurrent ovarian cancer, little evidence exists describing the benefit of third- line chemotherapy. The present authors previously reported that the treatment-free interval (TFI) after second-line chemotherapy may predict a survival benefit of third-line chemotherapy, however the length of TFI was uncertain due to limited cases. In this study, the authors evaluated the length of TFI, which is correlated with the effectiveness of third-line chemotherapy and a prognostic factor of third-line chemotherapy. MATERIALS AND METHODS: The authors reviewed the medical records of 85 women with recurrent ovarian cancer who received third-line chemotherapy after a paclitaxel/carboplatin (PC) regimen as first-line chemotherapy. RESULTS: The response rate [complete response (CR) + partial response (PR)] and clinical benefit rate [(CBR): CR + PR + stable disease (SD)] during the TFI after second-line chemotherapy for 0-3 months, 3-6 months, and 6-12 months and ≥ 12 months were 9.8%, 0%, 0%, 43.8% and 15.7%, 50%, 66.7%, and 93.8%, respectively. The median overall survival (OS) from the onset of third-line chemotherapy was longer for TFI ≥ 3 months than for TFI 0-3 months (795 days vs. 281 days, p < 0.001). Finally, according to univariate (HR = 0.256; p < 0.001) and multivariate (HR = 0.264; p < 0.001) analyses, TFI was the independent significant prognostic factor for OS. CONCLUSIONS: TFI less than three months after second-line chemotherapy may predict little survival benefit of third-line chemotherapy.

Gene expression profile of a newly established choriocarcinoma cell line, iC3-1, compared to existing choriocarcinoma cell lines and normal placenta.

Gestational choriocarcinoma is a malignant trophoblastic tumor that usually occurs in the uterus after pregnancy. The tumor is curable with advanced chemotherapy, but the molecular mechanism of choriocarcinoma tumorigenesis remains unclear. This is partly because the low incidence makes it difficult to obtain clinical samples for investigation and because an appropriate choriocarcinoma cell model to study the tumorigenesis has not been developed. We have established a new choriocarcinoma cell line, induced choriocarcinoma cell-1 (iC(3)-1), that possesses unique characteristics compared to other choriocarcinoma cell lines, including production of tumors that consist of the two types of cells commonly found in choriocarcinoma and mimicking of the clinical pathology. Existing trophoblast cell lines utilized in previous choriocarcinoma studies have had significantly dissimilar gene expression profiles. Therefore, it is important to choose an appropriate cell line for a particular study based on the characteristics of the cell line. In this study, to clarify the genetic characteristics of iC(3)-1 and to explore the tumorigenesis mechanism, we examined the gene profile of iC(3)-1 compared to those of existing cell lines and normal placental tissue. Bioinformatics analysis showed that several characteristic genes, IGF1R, CHFR, MUC3A, TAF7, PARK7, CDC123 and PSMD8, were significantly upregulated in iC(3)-1 compared to BeWo and JEG3 cells. Interestingly, HAS2, CD44 and S100P were significantly upregulated in iC(3)-1 compared to parental HTR8/SVneo cells and normal third trimester placenta. Choriocarcinoma samples also showed immunoreactivity to HAS2, CD44 and S100. In summary, the gene expression profile of iC(3)-1 suggests that studies using this cell line can make an important contribution to improved understanding of choriocarcinoma tumorigenesis.

Integrated solutions for urban runoff pollution control in Brazilian metropolitan regions.

One of the most important causes for poor water quality in urban rivers in Brazil is the low collection efficiency of the sewer system due to unforeseen interconnections with the stormwater drainage system. Since the beginning of the 20th century, Brazilian cities have adopted separate systems for sanitary sewers and stormwater runoff. Gradually these two systems became interconnected. A major challenge faced today by water managers in Brazil is to find efficient and low cost solutions to deal with this mixed system. The current situation poses an important threat to the improvement of the water quality in urban rivers and lakes. This article presents an evaluation of the water quality parameters and the diffuse pollution loads during rain events in the Pinheiros River, a tributary of the Tietê River in São Paulo. It also presents different types of integrated solutions for reducing the pollution impact of combined systems, based on the European experience in urban water management. An evaluation of their performance and a comparison with the separate system used in most Brazilian cities is also presented. The study is based on an extensive water quality monitoring program that was developed for a special investigation in the Pinheiros River and lasted 2.5 years. Samples were collected on a daily basis and water quality variables were analyzed on a daily, weekly or monthly basis. Two hundred water quality variables were monitored at 53 sampling points. During rain events, additional monitoring was carried out using an automated sampler. Pinheiros River is one of the most important rivers in the São Paulo Metropolitan Region and it is also a heavily polluted one.

Retrospective study comparing irinotecan and pegylated liposomal doxorubicin in treatment of recurrent platinum-refractory/resistant epithelial ovarian cancer.

PURPOSE: The standard regimen for platinum-resistant/refractory recurrent epithelial ovarian cancer (EOC) remains to be determined. In this study, we retrospectively compared the effect of irinotecan (CPT-11) and pegylated liposomal doxorubicin (PLD) in the treatment of platinum-resistant recurrent EOC. METHODS: Thirty patients who received salvage chemotherapy with CPT-11 or PLD were included in the study. CPT-11 (100 mg/m2) was administered intravenously on days 1, 8 and 15 every four weeks. PLD (50 mg/m2) was administered on day 1 every four weeks. Treatment was repeated, provided that no disease progression or intolerable toxicity occurred. RESULTS: Response rate in the CPT-11 group and PLD group showed no difference at 26.7% (p = 0.66) in both, while non-PD rate was 73.3% vs. 33.3% (p < 0.05), respectively. Progression-free survival after CPT-11 treatment and PLD treatment was 28.4 weeks and 16.8 weeks (p = 0.07), respectively. Hand-foot syndrome and mucositis were more common in the PLD group than in the CPT-11 group (p < 0.05). CONCLUSIONS: The results indicate that CPT-11 is a promising drug for the treatment of platinum-resistant recurrent EOC.

The chemosensitivity of nodal metastases in recurrent epithelial ovarian cancer.

PURPOSE: In this study, we compared second-line chemotherapy effects of nodal metastases with other metastases sites. METHODS: The medical records of 44 women with recurrent ovarian cancer who received second-line chemotherapy were retrospectively reviewed. RESULTS: Median age at the time of second-line chemotherapy was 55 years (range: 31-74). Recurrent sites were as follows: 29 patients had a solitary site (abdominal cavity: 8; lymph node: 3; pelvic cavity: 10; liver: 4; lung: 4) and 15 patients had multiple sites In total, the response rate was 30% (CR: 8, PR: 5). The response rate in sensitive cases was higher than in refractory/resistant cases (50% vs 5% p = 0.002). However, age, chemotherapy regimen, histologic type and number of diseases were not related with chemotherapy effect. In all diseases, response rate tended to be higher in lymph node disease than in the others (44% vs 27%). In both sensitive and refractory/resistant cases, response rate tended to be higher in lymph node disease. CONCLUSION: The response rate for lymph node diseases tended to be relatively high. Further study analyzing survival will be required to conclude the chemotherapy effect.

Effects of third-line chemotherapy for women with recurrent ovarian cancer who received platinum/taxane regimens as first-line chemotherapy.

PURPOSE: At present, it remains unclear whether the third-line chemotherapy has clinical benefit. In this study, we retrospectively evaluated the effect of third-line chemotherapy. METHODS: We reviewed the medical records of 40 women with recurrent epithelial ovarian cancer (EOC) who received third-line chemotherapy after platinum/taxan regimens as first line chemotherapy. RESULTS: In the first recurrence, 23 cases were platinum-sensitive and 17 cases were platinum-resistant. The cases for which the treatment-free interval from second-line chemotherapy (TFI) was a 3 months had a higher non-PD rate than those with TFI < 3 months (86% vs 33%, p = 0.002). In addition, the median overall survival (OS) was longer for TFI > or = 3 months than for TFI < 3 months (1195 days vs 235 days, p = 0.004). Finally, TFI was an independent significant prognostic factor by univariate (HR 3.28, p = 0.006) and multivariate (HR 3.21, p = 0.018) proportional hazard tests. CONCLUSION: TFI from second-line chemotherapy may predict a survival benefit of third-line chemotherapy.

Prognosis of Japanese patients with ovarian clear cell carcinoma associated with pelvic endometriosis: clinicopathologic evaluation.

OBJECTIVE: Ovarian clear cell carcinoma is commonly associated with pelvic endometriosis. We retrospectively evaluated clinicopathological data on the association between ovarian clear cell carcinoma and pelvic endometriosis. METHODS: Between 1984 and 1995, we evaluated clinicopathological data on 53 Japanese patients with primary ovarian clear cell carcinoma who had been initially treated at Keio University Hospital. The clinical backgrounds and 5-year survival rates were evaluated. RESULTS: Twenty (37.7%) of the 53 patients had carcinoma accompanied by pelvic endometriosis. These 20 cases were classified as FIGO stage I (n = 13, 65%), stage II (n = 1, 5%), stage III (n = 6, 30%), or stage IV (n = 0). The other 33 cases of ovarian clear cell carcinoma had no evidence of association with endometriosis and were classified as stage I (n = 19, 57.6%), stage II (n = 2, 6.1%), stage III (n = 9, 27.2%), or stage IV (n = 3, 9.1%). The incidence of a positive intraperitoneal cytology in stage Ic was significantly less in the group with endometriosis than in that without the endometriosis (n = 1, 14.3% vs n = 9, 64.3%, P = 0.03). The 5-year survival rate of stage I patients was significantly greater in ovarian clear cell carcinoma with pelvic endometriosis (100%) than in that without it (60%, P < 0.05). CONCLUSION: Patients having ovarian clear cell carcinoma with pelvic endometriosis exhibited a better prognosis than those without endometriosis, especially those patients with stage I cancer.

Monoclonal antibody ONS-M21 recognizes integrin alpha3 in gliomas and medulloblastomas.

The monoclonal antibody ONS-M21 recognizes an antigen found on the surface of glioma and medulloblastoma cells but does not react with the antigens of normal brain tissue. We purified and identified the 140-kDa protein by means of an antibody-binding affinity column. This 140-kDa antigen has sequences homologous to the amino-terminal region and five parts of the internal domain of integrin alpha3. When the integrin alpha3-related sequences was amplified and used to analyse the mRNA of glioma and medulloblastoma surgical specimens, the transcription level of integrin alpha3 mRNA appeared to be quantitatively correlated with the grade of malignancy. These findings suggest that the ONS-M21 antibody, which reacts with integrin alpha3, might be useful in the diagnosis of gliomas and medulloblastomas.

[Clinical study on the time courses of serum myosin light chain I levels in patients with acute myocardial infarction: effect of intracoronary thrombolysis on serum myosin light chain I levels].

Changes of serum myosin light chain I (Myosin LCI) concentrations and CK activities were serially measured in 23 patients with acute myocardial infarction. Intracoronary thrombolysis was performed in 14 patients (ICT group) while the remaining 9 patients were treated in the conventional manner (non ICT group). The relationships between the maximum levels of serum Myosin LCI or CK and a myocardial infarct size index or left ventricular function were evaluated in 18 patients. The myocardial infarct size index was determined by 201Tl myocardial scintigrams performed in the chronic phase. Multiple peaks of Myosin LCI were observed in 64% (9/14) of the ICT group and the first peak in 6 of these patients appeared Much earlier in the same time as CK peak than in the non-ICT group, while multiple peaks were seen only in one case in the non-ICT group. The infarct size index by 201Tl myocardial SPECT correlated with maximum Myosin LCI levels (r = 0.88, p < 0.001, n = 10) and CK activities (r = 0.67, p < 0.05, n = 10). These results indicate that the measurement of serum Myosin LCI is very useful for estimating the extent of myocardial damage and suggest that myocardial degeneration occurs at a very early phase of myocardial infarction.

[The early detection of metastatic differentiated thyroid cancer using 131I total body scan and treatment with 131I].

With the purpose of achieving early detection and performing 131I therapy for metastatic lesions of differentiated thyroid cancer, we studied the clinical findings in 132 patients who underwent 131I total body scanning (131I TBS) between 1981 and 1990. Metastatic lesions were detected only by 131I TBS in 24 (18%) of the 132 patients. Of the 49 patients treated with 131I for metastases, 27 (55%) underwent total thyroidectomy and then had their metastatic lesions treated by 131I less than one year later. In the remaining 22 patients (45%), the metastatic lesions were treated with 131I from 1 to 31 years (mean: 8.4 years) after the initial thyroidectomy. We determined the optimal timing of 131I TBS following radical thyroidectomy to be 3-4 weeks by sequential measurement of the serum thyroid hormones, TSH, and Tg, and determination of the 123I uptake in residual or metastatic cancer of the neck after thyroidectomy. 131I TBS with simultaneous serum Tg determination were performed in 52 patients with metastases. Scans were positive in 43 of the 52 (83%) and the serum Tg level was greater than 10 ng/ml in 46 of the 52 (88%). Serum Tg was elevated in 9 patients with negative scans, while low Tg levels were found in 6 patients with positive scans. 131I therapy was effective in 49 of the 65 treated patients (75%), including 5 cures. Two patients worsened and 6 died. These 8 patients were all older than 56 years of age. Post-therapeutic 131I TBS demonstrated unsuspected metastatic lesions in 7 patients and had a higher detection rate for metastatic lesions than diagnostic 131I TBS. We conclude that 131I TBS with simultaneous Tg determination should be performed to detect metastatic lesions in all patients following positively total thyroidectomy for differentiated thyroid cancer, and that 131I treatment should be given when positive 131I uptake is detected in metastatic or residual cancer.