Prevalence of cervical HPV and attitude towards cervical screening in IBD patients under immunomodulatory treatment: a multidisciplinary management experience.

OBJECTIVE: Therapeutic strategies for Inflammatory Bowel Diseases (IBD: Crohn's disease and Ulcerative Colitis) have improved but the risk for HPV infection in patients under immunomodulatory/biologic treatment is unclear. Objective of the study is to identify the attitude of patients and caregivers to cervical screening. To determine the prevalence of HPV and cervical lesions in IBD patients receiving immunomodulatory/biological treatment. PATIENTS AND METHODS: IBD patients treated with immunomodulators were enrolled from November 2016 to September 2017, thanks to a multidisciplinary cooperation. A survey was administered to enrolled patients as well as to a selected network of IBD expert physicians. Patients who consented underwent gynecological examination, smear, HPV DNA test, colposcopy, vaginal and cervical microbiological swabs. RESULTS: 294 patients from AMICI Onlus Association, 119 patients from the hospital clinic, 30 doctors from national IBD centers participated to the survey. 19 patients from the IBD clinic underwent cervical screening. More than 90% of doctors consider their patients at risk of cervical cancer. A low prevalence of high-risk genotypes and related HPV lesions and an increased prevalence of bacterial vaginosis emerged in the studied population. CONCLUSIONS: Biological drugs could lead to a positive immunomodulation towards HPV infection. In IBD patients an alteration of the vaginal and intestinal microbiota seems to be coexisting.

Locally advanced cervical cancer complicating pregnancy: A case of competing risks from the Catholic University of the Sacred Heart in Rome.

A case of stage IB2 cervical cancer at 27 weeks of pregnancy, treated with neoadjuvant chemotherapy followed by radical Cesarean hysterectomy with full pelvic and infra-mesenteric lymphadenectomy, and adjuvant chemo-radiation is described. While she remains without disease, her baby was diagnosed with acute myelogenous leukemia. We highlight the pre-operative work-up, treatment options, safety, feasibility, and outcomes for the mother and her fetus.

Paclitaxel, epirubicin, and cisplatin (TEP) regimen as neoadjuvant treatment in locally advanced cervical cancer: long-term results.

OBJECTIVE: We evaluated the rates of response, operability and long term survival and toxicities in a large series of locally advanced cervical cancer (LACC) patients administered neoadjuvant chemotherapy (NACT) with paclitaxel, epirubicin and cisplatin (TEP) followed by radical surgery (RS). Patients and methods The study included 75 consecutive stages IB2-IVA patients administered NACT with paclitaxel (175mg/m(2)), epirubicin (100mg/m(2)) and cisplatin (100mg/m(2)) on day 1 of a 3-weekly cycle for 2-4cycles. Patients were evaluated for objective response by RECIST criteria and triaged to RS. Progression-free survival (PFS) and overall survival (OS) were calculated from the date of diagnosis to recurrence/progression of disease or death, respectively. RESULTS: Complete and partial clinical response was observed in 13 and 28 patients (56.1% objective responses); radical surgery was amenable in 52 patients (71.2%): 14 patients showed complete/microscopic response to treatment. Overall, recurrence/progression of disease was observed in 36 patients, and all of them experienced death of disease. In the whole series median PFS was 48months (5-year PFS=51.0%), and median OS was 72months (5-year OS=53.0%). Overall, 195 courses were administered; treatment was delayed in 6.7% of patients, while dose reduction was required in 36.5% of patients. Grade 3 leukopenia affected 22 patients (29.7%), while Grades 3 and 4 neutropenia was documented in 17 (22.9%) and 6 (8.1%) patients. In the whole series, we recorded 1 death whose relation with treatment-induced toxicity could not be ruled out. CONCLUSIONS: TEP provided favorable rates of response and operability in LACC patients, and allowed the obtainment of encouraging survival data without carrying out an excessive toxicity.

Phase II study of NGR-hTNF in combination with doxorubicin in relapsed ovarian cancer patients.

BACKGROUND: The NGR-hTNF (asparagine-glycine-arginine-human tumour necrosis factor) is able to promote antitumour immune responses and to improve the intratumoural doxorubicin uptake by selectively damaging tumour blood vessels. METHODS: Patients progressing after ≥ 1 platinum/taxane-based regimen received NGR-hTNF 0.8 µg m(-2) and doxorubicin 60 mg m(-2) every 3 weeks. Primary endpoint was a Response Evaluation Criteria in Solid Tumors-defined response rate with a target of more than 6 out of 37 responding patients. RESULTS: A total of 37 patients with platinum-free interval lower than 6 months (PFI<6; n=25), or between 6 and 12 months (PFI=6-12; n=12) were enrolled. Median baseline peripheral blood lymphocyte count (PBLC) was 1.6 per ml (interquartile range, 1.2-2.1). In all, 18 patients (49%) received more than 6 cycles. Febrile neutropaenia was registered in one patient (3%). Among 35 assessable patients, 8 (23%; 95% CI 12-39%) had partial response (2 with PFI<6; 6 with PFI=6-12) and 15 (43%) had stable disease (10 with PFI<6; 5 with PFI=6-12). Median progression-free survival (PFS) was 5.0 months for all patients, 3.8 months for patients with PFI<6, and 7.8 months for patients with PFI=6-12. Median overall survival (OS) was 17.0 months. Patients with baseline PBLC higher than the first quartile had improved PFS (P=0.01) and OS (P=0.001). CONCLUSION: Tolerability and activity of this combination warrant further randomised testing in patients with PFI<6. The role of PBLC as a blood-based biomarker deserves further investigation.

Docetaxel and oxaliplatin in the second-line treatment of platinum-sensitive recurrent ovarian cancer: a phase II study.

BACKGROUND: A prospective phase II study was conducted to evaluate the efficacy and toxicity of the combination docetaxel (Taxotere) (DTX) and oxaliplatin (OXA) in ovarian cancer patients recurring after a platinum-free interval (PFI) >12 months. PATIENTS AND METHODS: DTX, 75 mg/m(2), was administered by 60 min i.v. infusion, followed by OXA, 100 mg/m(2), given by a 2 h i.v., on day 1 every 21 days. RESULTS: From October 2003 to June 2006, 43 ovarian cancer patients were enrolled. Median PFI was 26 months. All patients were available for response evaluation: 17 complete responses and 12 partial responses were registered, for an overall response rate of 67.4%. The median response duration was 10 months. Stable disease was documented in 11 patients (median duration = 5.5 months). The median time to progression and overall survival were 14 and 28 months. A total of 259 courses were administered. Grade 3-4 leukopenia was documented in 32.5% of the patients, while no case of severe anemia and thrombocytopenia was observed. Grade 3-4 neurotoxicity and grade 2 alopecia were observed in 9.3% and 34.9% of cases, respectively. CONCLUSION: DTX/OXA combination is an active regimen with a favorable toxicity profile, for treatment of recurrent platinum-sensitive ovarian cancer patients.

In vitro evaluation of newly developed chalcone analogues in human cancer cells.

PURPOSE: Among flavonoids, chalcones have been identified as interesting compounds having chemopreventive and antitumor properties. We studied a panel of newly developed chalcone analogues (S1-S10) using MDA-MB 231 and MCF-7 ADRr breast cancer cells and the T-leukemic Jurkat cell line. Quercetin was used as the reference compound. METHODS: Antiproliferative activity was evaluated by cell counts performed after 72 h of exposure to the drugs. DNA analysis and redox activity were evaluated using flow cytometry. Apoptosis was assessed by morphological analysis, using YOYO-1 as DNA dye; p-glycoprotein function was ascertained by quantitating the efflux of rhodamine 123. RESULTS: All cells were sensitive to chalcone analogues yielding IC50 in micromolar concentrations with the following order regardless of the multidrug resistance (MDR) status: S1 > S2 > quercetin. S1 and S2, the most active compounds, were selected to evaluate their effect on the cell cycle, apoptosis, redox activity, and modulation of the p-glycoprotein function. No significant perturbation in cell cycle was seen with concentration up to 1 microM after 24 h. After 72 h a slight increase in G2/M block and DNA fragmentation occurred at 10 microM. Morphological analysis of apoptosis showed that chalcone analogues induced apoptosis to a higher extent than quercetin. Redox analysis demonstrated that all substances were able to increase intracellular thiol levels, which returned to baseline value after 24 h for all drugs except quercetin. Production of reactive oxygen species was essentially unaffected by all compounds. Finally, in MDR-positive MCF-7 ADRr cells chalcone analogues were unable to modulate p-glycoprotein function while quercetin was able to. CONCLUSIONS: Newly developed S1 and S2 chalcones have a different but higher antitumor activity than quercetin and could be considered as potential new anticancer drugs.

Antagonistic effect of the combination gemcitabine/topotecan in ovarian cancer cells.

The in vitro interaction between the new antimetabolite gemcitabine (GEM) and topotecan (TPT) was analyzed in A2780 ovarian cancer cells. The growth inhibitory effect was assessed after 3 days of drug exposure. GEM and TPT obtained in vitro IC50 values of 2.1 +/- 0.9 and 33.7 +/- 10.2 nM, respectively. The interaction between GEM and TPT was evaluated by exposing cancer cells at increasing doses of GEM (0.1, 1, and 10 nM) and TPT (1, 10, 100, and 1000 nM). Analysis of data about the interaction between GEM and TPT was performed by applying the isobole method. An antagonistic effect was noticed when GEM was combined with TPT in the tested concentration range. DNA analysis was also performed and showed an augmentation of cells blocked in the G2/M phase during TPT exposure, while an increase of blocked cells in the G0/1, phase was observed after GEM treatment. This latter effect was predominant when the two drugs were used in combination. We also investigated the effect of sequential exposure to drugs, pretreating A2780 cells for 24 h with TPT and then for 48 h with GEM, and, conversely, pretreating A2780 cells with GEM for 24 h and thereafter with TPT for 48 h. Both these combined sequential treatments showed an antagonist effect of the drugs' combination. Long-term growth inhibition effect was established by clonogenic assay performed after 10 days of culture after drug treatment. Also these data confirmed the antagonistic effect between GEM and TPT in A2780 ovarian cancer cells.

N-deacetyl-N-aminoacylthiocolchicine derivatives: synthesis and biological evaluation on MDR-positive and MDR-negative human cancer cell lines.

A new series of N-deacetyl-N-(N-trifluoroacetylaminoacyl)thiocolchicine derivatives 9-15 have been synthesized starting from the corresponding N-deacetylthiocolchicine (3) and the N-trifluoroacetylamino acids 5-8 which were used as a racemic mixture. The trifluoroacetyl protecting group has been removed easily, giving the corresponding N-deacetyl-N-aminoacylthiocolchicines 16-22. Optical pure compounds 9-22 were isolated from the diastereoisomeric mixture or were prepared starting from compound 3 and an optical pure amino acid derivative; the configuration of each compound was assigned unequivocally. The diastereoisomeric couples of amino acids synthesized were tested, and their antiproliferative activity on MDR-positive and MDR-negative human cancer cell lines was evaluated.

Biological evaluation on different human cancer cell lines of novel colchicine analogs.

Three new 7-0-substituted deacetamidothiocolchicine derivatives have been evaluated for their antitumor activity against various human tumor cell lines, some of which express the multidrug resistance (MDR) phenotype, for their impact on the cell cycle and their binding to tubulin. Colchicine and thiocolchicine were used as reference compounds. Thiocolchicine was the most active agent on MDR-negative cells in terms of growth inhibition, whereas for multidrug-resistant cells, thiocolchicone was the most active compound (IC50 = 14 nM). As indicated by statistical analysis, a perfect agreement for the potency order (IC50 values) of the compounds between all the MDR-negative cancer cells (k = 1.00), a poor agreement between MDR-positive and MDR-negative cancer lines, and a moderate agreement (k = 0.50) between the two resistant cancer cells MCF-7 ADRr and CEM VBL were observed. To gain further insight into the mechanism of the antitumor activity of colchicinoids, the most active compounds, colchicone and thiocolchicone, were selected to evaluate their effect on cell cycle, apoptosis, and tubulin interaction. The highest recruitment activity into the G21/M phase of the cell cycle was detected in thiocolchicone-treated breast cancer cells. Interestingly, after 72 h of culture, when the cell cycle block subsided, a consistent amount of DNA fragmentation, a hallmark of apoptosis, was evident. Morphological analysis of MCF-7 ADRr cells confirmed this hypothesis and revealed that thiocolchicone was able to induce apoptosis in this MDR-bearing model. We also demonstrated, using flow cytometry, that thiocolchicone interacts with alpha- and beta-tubulin, thereby affecting the expression of both subunits.

Antitumor activity of paclitaxel (taxol) analogues on MDR-positive human cancer cells.

A series of newly developed paclitaxel analogues have been tested for their growth inhibitory activity on two human breast cancer cell lines, one of which expresses the MDR (multidrug resistance) phenotype. Paclitaxel (taxol) was used as a reference compound. Three new classes of taxanes were analyzed: the cephalomannine compounds, the pyrazoline derivatives and the seco-derivatives. Our results demonstrated an increased antiproliferative activity of pyrazoline derivatives on drug-resistant cancer cells with respect to paclitaxel. These compounds were able to block MDR-bearing MCF-7 ADRr cells in the G2/M phase of cell cycle and, consequently, induce programmed cell death. In keeping with the antiproliferative effects, cells treated with paclitaxel derivatives showed a more pronounced cell cycle arrest than the parent compound paclitaxel. Also, apoptotic cell death, calculated as a percent of DNA fragmentation, occurred to a greater extent in cells exposed to pyrazoline derivatives. The development of new paclitaxel analogues with greater antitumour activity on MDR-positive cells may be useful in selecting new taxanes effective on resistant tumors.

[Therapy of bacterial vaginosis. Prospective clinical study ot the efficacy and tolerability of quaternary ammonium salts vs. clindamycin]. / La terapia delle vaginosi batteriche. Studio clinico prospettico sull'efficacia e tollerabilità dei sali quaternari d'ammonio versus clindamicina.

BACKGROUND: To evaluate the efficacy and safety of intravaginal quaternary ammonium antimicrobial compounds (SQA) versus clindamycin 2% intravaginal cream (CL) in the treatment of bacterial vaginosis (VB). MATERIALS AND METHODS: One hundred-thirty-three patients affected by VB were enrolled in the study from January 1995 to October 1997. Patients were classified according to Amsel's criteria and/or to the indications of the Scandinavian Society of Bacterial Vaginosis. Twenty-three patients were initially excluded from the study, and 110 patients were randomized in two groups, SQA versus CL. Patients were reevaluated after 3 weeks, 3 months and 6 months from the end of therapy. The safety of treatment was also investigated. RESULTS: Of 110 patients, 59 were treated with SQA and 51 with CL. One hundred (90.9%) patients completed the therapy and were subjected to the first control after 3 weeks from the end of therapy. A significant reduction of most of the symptoms and all signs of VB was observed in the group treated with SQA. Similarly, a significant reduction of most of the symptoms (vaginal and urinary in particular) and all signs of VB was observed in the group treated with CL. The percentage of response was 86.7% for SQA group and 87.2% for CL group. Moreover, after 3 months from the end of therapy, 47.2% and 50% of the patients treated with SQA and CL, respectively, recurred, and after 6 months 78.5% and 75% of the patients recurred, respectively. CONCLUSIONS: SQA treatment conferred 86.7% of response after 3 weeks from the end of therapy, with poor side effects and a good compliance in good keeping with the results obtained with CL treatment.

Antiproliferative activity of colchicine analogues on MDR-positive and MDR-negative human cancer cell lines.

In this study the in vitro antitumor activity of a series of 20 colchicine analogues was tested and compared with colchicine and thiocolchicine on three different human cancer cell lines, two of which express the multidrug-resistance (MDR) phenotype. At concentrations from 1 nM to 100 microM, all compounds tested inhibited cancer cell proliferation. The IC50 values indicate that the three fluorinated analogues were the most active compounds, with a similar decreasing order of potency (IDN 5005 > IDN 5079 > IDN 5080) on the two MDR-expressing cell lines, whereas thiocolchicine was the most effective compound on the MDR-negative MDA-MB 231 cells. A strong correlation (r = 0.94; P = 0.004) was found between IC50 values obtained using the two MDR-positive cell lines. Conversely, IC50 values obtained in MDA-MB 231 cells did not show a significant correlation with MDR-positive cell lines, thereby suggesting some difference in the antiproliferative mechanism(s) of colchicine analogues. Cell cycle analysis of the most active analogues in breast cancer cells showed a relationship between cell cycle blocking activity and growth inhibition. The most active agents on the MDR-positive MCF7 ADRr cell line, after 24 h of culture, in terms of cell cycle blocking activity were the three fluorinated analogues. Interestingly, after 72 h, when the cell cycle block subsided, a consistent amount of DNA fragmentation was evident. The extent of cell cycle block, measured as the G2/G1 ratio, was significantly correlated with the apoptosis rate expressed as a percentage of DNA fragmentation on both cell lines, thereby suggesting that a large number of blocked cells underwent the apoptotic pathway.

Anti-proliferative activity of a new class of taxanes (14beta-hydroxy-10-deacetylbaccatin III derivatives) on multidrug-resistance-positive human cancer cells.

Paclitaxel, docetaxel and a series of new analogs synthesized from 14beta-hydroxy-10-deacetylbaccatin III (14-OH-DAB), a natural diterpene closely related to the core synthon of the 2 above prototypes, were tested in vitro for their growth-inhibitory activity on different human cancer cell lines, including some expressing the classic multidrug-resistant (MDR) phenotype (MCF-7 ADRr and CEM VBLr). The 14-OH-DAB derivatives showed enhanced anti-proliferative activity as compared to the parent compounds on the MDR-positive cancer cell lines. Particularly, IDN 5109 showed a 25- to 30-fold higher activity than paclitaxel. The fold change in activity between paclitaxel and analogs (IC50 paclitaxel/IC50 analogs) on the MDR-positive cell lines was calculated and a significant correlation observed. As far as the MDR-negative MDA-MB 231 cells are concerned, docetaxel and IDN 5109 exhibited a more potent activity than paclitaxel. On the basis of the data obtained on cell growth inhibition, we selected the most active compounds to study their effect on the cell cycle. Cell cycle analysis showed that all of the compounds tested were able to induce cell cycle block at G2/M in a concentration-dependent manner. The amount of cell block, measured as a G1/G2 ratio, was correlated significantly (p < 0.001) with apoptosis, as evaluated in the sub-G1 region (% of DNA fragmentation), thereby suggesting that the G2/M-blocked cells underwent apoptosis. To confirm the occurrence of apoptosis in this system, DNA gel agarose electrophoresis was performed and showed the typical ladder pattern.

Tamoxifen synergizes the antiproliferative effect of cisplatin in human ovarian cancer cells: enhancement of DNA platination as a possible mechanism.

We investigated the chemosensitizing activity of tamoxifen (TAM) on estrogen receptor negative ovarian cancer cell lines sensitive (A2780 WT) and resistant to cisplatin (CP) (A2780 CP3). Our results showed that the treatment of both cell lines with the association TAM + CP (concentration range 0.01-1 microN and 0.1-1 microgram/ml, respectively) results in a synergistic antiproliferative activity and a complete reversal of the acquired CP-resistant phenotype. We demonstrated that in A2780 cells the addition of TAM to CP treatment is able to significantly enhance at every tested CP dose (P < 0.001) the amount of platinum (Pt) bound to the DNA. Since Pt-DNA levels in the genome are clearly related to the growth inhibitory effect of CP (correlation value = 0.97, P < 0.001) in our experimental model, we hypothesized that TAM could act synergistically with CP and overcome the acquired CP-resistance by enhancing Pt binding to the DNA. We suggest that, from a clinical point of view, TAM may be usefully included in CP-based chemotherapy regimens for ovarian cancer patients since plasma concentrations of the drug capable of in vitro CP resistance modulation are achievable in vivo. A prospective clinical trial to verify the clinical usefulness of combined TAM + CP treatment in ovarian cancer patients refractory to prior Pt-based chemotherapy is now underway in our department.

Modulatory effect of tamoxifen and ICI 182,780 on adriamycin resistance in MCF-7 human breast-cancer cells.

In this study the ability of the new pure anti-estrogen ICI 182,780 to modulate the cytotoxic action of adriamycin (ADR) on parental and ADR-resistant MCF-7 (MCF-7 ADRr) human breast-cancer cells was investigated and compared with that of tamoxifen (TAM). TAM enhanced ADR cytotoxicity in MCF-7 ADRr cells in a dose-related manner, but this effect was slight or absent in MCF-7 WT. In contrast, ICI 182,780 was able to enhance ADR toxicity both in MCF-7 ADRr and in the parental cell line. ICI 182,780 was up to 2.5-fold more effective than TAM in reducing the IC50 of ADR in MCF-7 ADRr cells. Analysis of the data by the isobole method showed that the combination ADR/TAM and ADR/ICI 182,780 produced synergistic anti-proliferative activity in MCF-7 ADRr cells. Because ADR resistance in these cells is associated with the expression of high levels of P-glycoprotein (Pgp), we evaluated the effect of anti-estrogens on Pgp expression and activity. Both ICI 182,780 and TAM failed to modulate Pgp expression as assessed by flow cytometry and Western-blot analysis, performed using the monoclonal antibodies MM4.17 and C 219, which are specific for an external or an internal determinant respectively. Pgp activity was investigated by flow cytometry measuring the extrusion of ADR and the cationic dye Rhodamine 123 (Rh 123). ICI 182,780, but not TAM, reduced the activity of Pgp in MCF-7 ADRr cells. Flow cytometry was also used to investigate cell-cycle modifications induced by ADR in MCF-7 ADRr cells, both in the presence and in the absence of anti-estrogens. After 72 hr, higher doses induced an arrest of cells at the G2/M phase. The same effect was visible when lower doses of ADR were combined with ICI 182,780 or TAM. In terms of cell-cycle-blocking activity ICI 182,780 was largely more effective than TAM.

Antiproliferative effect of silybin on gynaecological malignancies: synergism with cisplatin and doxorubicin.

The aim of this study was to test the antiproliferative activity of silybin, a flavonoid, on human ovarian and breast cancer cell lines. Since flavonoids are thought to act through Type II oestrogen binding sites (Type II EBS), silybin binding to Type II EBS was also examined. Silybin, used in concentrations from 0.1 to 20 microM, exerted a dose-dependent growth inhibitory effect on OVCA 433, A2780 parental and drug-resistant ovarian cancer cells, and MCF-7 doxorubicin (DOX)-resistant breast cancer cells (IC50 = 4.8-24 microM). Both L and D diastereoisomers of silybin were effective in inhibiting A2780 WT cell growth (IC50 = 14 and 20 microM, respectively). Flow cytometry revealed that silybin decreased the percentage of cells in the S and G2-M phases of the cell cycle with a concomitant increase in cells in the G0-G1 phase. Silybin was able to compete with [3H]E2 for nuclear but not cytosolic Type II EBS. Its affinity parallels its efficacy in inhibiting cell proliferation. Furthermore, silybin (0.1 and 1 microM) potentiates the effect of cisplatin (CDDP) (0.1-1 micrograms/ml) in inhibiting A2780 WT and CDDP-resistant cell growth. Similar results were obtained on MCF-7 DOX-resistant cells when silybin (0.1 microM) was associated with doxorubicin (0.1-10 micrograms/ml). As assessed by the Berembaum isobole method, the effect of silybin-CDDP and silybin-DOX combinations results in a synergistic action. Using the 'stem cell assay' described by Hamburger and Salmon [Science 1977, 197, 461-463], we found that silybin exerted a dose-dependent inhibition of clonogenic efficiency of cells derived from three ovarian tumours (IC50 = 7.4, 4 and 6.4 microM, respectively). Since CDDP and DOX are the two most commonly used drugs for gynaecological tumours, the clinical application of silybin is currently under investigation in our institute.

Effect of synthetic and naturally occurring chalcones on ovarian cancer cell growth: structure-activity relationships.

This study was carried out to determine the effect of 15 different natural and synthetic chalcones on the proliferation of both established and primary ovarian cancer cells expressing type II oestrogen binding sites (type II EBS). The binding affinity of chalcones for type II EBS was also tested. At concentrations from 0.1 to 10 microM, chalcones inhibited ovarian cancer cell proliferation and [3H]oestradiol ([3H]E2) binding to type II EBS. Considering the structure-related variation in IC50 (concentration resulting in a 50% inhibition of cell growth) and Di50 (concentration resulting in a 50% displacement of [3H]E2 bound to type II EBS), it appeared that the presence of an alpha-beta double bond, the hydroxylation in 3 or 2 of ring B and the absence of a prenyl group were important to both the antiproliferative and binding activity. Structure-related variations in IC50 and Di50 were significantly concordant (Fisher's exact test: P = 0.0291), suggesting that there may be a type II EBS-mediated mechanism for chalcone antiproliferative activity. Our data indicate that chalcones could be considered as potential new anticancer drugs.

Methyl-p-hydroxyphenyllactate-esterase activity and type-II estrogen-binding sites in ovarian cancer: correlation with biological and clinico-pathological parameters.

We examined the levels of activity of methyl-p-hydroxyphenyllactate esterase (MeHPLA-ase) and cytosolic Type-II-estrogen-binding sites (Type-II EBS) in 61 and 71 cases, respectively, of primary ovarian cancer. MeHPLA-ase activity and Type-II EBS were seen to by asymmetrically distributed, in that levels were skewed towards the lower values. A statistically significant direct correlation was found between MeHPLA-ase activity and Type-II EBS. MeHPLA-ase activity and Type-II EBS were inversely correlated with ER and PR levels and showed a trend towards inverse correlation with the percentage of cells in S-phase of the cell cycle. MeHPLA-ase activity and Type-II EBS did not correlate with clinico-pathological parameters. The median MeHPLA-ase activity tended to be higher in responders than in unresponsive patients, but statistical significance was not reached. Higher Type-II-EBS levels were found in cases showing complete and partial response to chemotherapy than in cases which did not respond. A statistically significant relationship was found between high MeHPLA-ase activity and longer overall survival.