Phase II study of the combination carboplatin plus celecoxib in heavily pre-treated recurrent ovarian cancer patients

Cyclooxygenase-2 overexpression is associated with poor outcome and resistance to platinum-based chemotherapy in ovarian cancer. We evaluated the antitumor activity and safety of the combination carboplatin plus the COX-2 inhibitor celecoxib in recurrent heavily-treated OC patients

Nm23 expression in endometrial and cervical cancer: inverse correlation with lymph node involvement and myometrial invasion.

The expression of nm23 has been shown to correlate in some solid tumours with their metastatic potential and to be associated with a favourable prognosis in human breast cancer and melanoma. In breast and ovarian cancer nm23 expression is also correlated with lymph node involvement. We analysed the expression of nm23-H1 and -H2 in normal endometrium and in endometrial and cervical cancer by both Northern and Western blotting. Cellular localisation of Nm23-H1 was visualised by immunohistochemistry mostly in the cytoplasm. Both isoforms of Nm23 were present in all the samples analysed, and a clear direct correlation between Nm23-H1 and -H2 levels was evident. Median nm23-H2 levels were higher than than -H1 levels in both tissues. Cervical cancer patients with lymph node involvement were shown to have significantly lower protein levels of Nm23 (P < 0.007 for H1 and P < 0.009 for H2), and a similar trend was also evident in endometrial cancer. Furthermore, the degree of myometrial invasion in endometrial cancer patients was also inversely correlated with Nm23-H1 levels of expression (P < 0.003). Nm23 level may therefore be taken into consideration as a new marker in the prognostic characterisation and in the treatment planning of uterine tumour patients

The GOODSTEP project: General Object-Oriented Database for Software Engineering Processes

The goal of the GOODSTEP project is to enhance and improve the functionality of a fully object-oriented database management system to yield a platform suited for applications such as software development environments (SDEs). The baseline of the project is the O2 database management system (DBMS). The O2 DBMS already includes many of the features regulated by SDEs. The project has identified enhancements to O2 in order to make it a real software engineering DBMS. These enhancements are essentially upgrades of the existing O2 functionality, and hence require relatively easy extensions to the O2 system. They have been developed in the early stages of the project and are now exploited and validated by a number of software engineering tools built on top of the enhanced O2 DBMS. To ease tool construction, the GOODSTEP platform encompasses tool generation capabilities which allow for generation of integrated graphical and textual tools from high-level specifications. In addition, the GOODSTEP platform provides a software process toolset which enables modeling, analysis and enaction of software processes and is also built on top of the extended O2 database. The GOODSTEP platform is to be validated using two CASE studies carried out to develop an airline application and a business application

Epithelial ovarian cancer relapsing as isolated lymph node disease: natural history and clinical outcome

<p>Abstract</p> <p>Background</p> <p>Several evidences suggested that ovarian cancer (OC) patients showing isolated lymph node recurrence (ILNR) have an indolent evolution. The aim of the study was to retrospectively review ILNR observed in our Institution over the past 11 years in order to investigate: the pattern of disease progression after the first diagnosis of ILNR, and their clinical outcome.</p> <p>Methods</p> <p>Between September 1995 and September 2006, 523 epithelial OC were diagnosed in our centers, and 301 of these relapsed. Cases with a diagnosis of ILNR, and at least 12 months of follow up after the diagnosis of ILNR were included. Post-relapse survival (PRS) was recorded from the date of the diagnosis of ILNR to the date of death or date last seen. Survival probabilities were estimated according to the method of Kaplan and Meier and compared by the log rank test. Cox's regression model with stepwise variable selection was used to analyse the role of clinico-pathological parameters as prognostic factors for PRS.</p> <p>Results</p> <p>Thirty-two cases were identified as ILNR (10.6% of the recurrences, and 6.1% of the OC population). Most of the patients continued to exhibit the same pattern of progression during follow up, with 75% of the patients free from peritoneal disease after 2 years from the diagnosis of ILNR. Median Post-Relapse Survival (PRS) was 37 months, and median Overall Survival (OS) was 109 months, with all patients surviving more than 2 years after the initial diagnosis. In multivariate analysis only Platinum-Free Interval (PFI) retained a prognostic role for PRS (p value = 0.033).</p> <p>Conclusion</p> <p>ILNR represents a less aggressive pattern of OC relapse which keeps progressing in the lymph nodes in a relatively high percentage of cases. On the other hand, the occurrence of peritoneal spreading after ILNR is associated with a rapidly fatal outcome.</p

Inhibitory effect of quercetin on OVCA 433 cells and presence of type II oestrogen binding sites in primary ovarian tumours and cultured cells.

We investigated the effect of the flavonoid quercetin (Q) on the proliferation of the ovarian cancer cell line OVCA 433. Growth experiments demonstrated that Q exerted a reversible dose-dependent inhibition of cell proliferation in the range of concentrations between 10 nM and 10 microM. Two other flavonoids tested, rutin and hesperidin, were ineffective in inhibiting cell growth. Cell cycle analysis showed that the growth inhibitory effect of Q was due to a blocking effect in the GO/G1 phase. Using a whole cell assay with (6.7-3H) oestradiol (3H-E2) as tracer we demonstrated that OVCA 433 cells contain type II oestrogen binding sites (type II EBS). Competition analysis showed that Q competed for 3H-E2 binding to type II EBS while both rutin and hesperidin did not. Appreciable amounts of type II EBS were also detected in seven primary ovarian tumours. Our results suggest that Q may regulate ovarian cancer cell growth through a mechanism involving a binding interaction with type II EBS. This mechanism could also be active in vivo since primary ovarian tumours contain type II EBS

Role of minimally invasive surgery versus open approach in patients with early-stage uterine carcinosarcomas: a retrospective multicentric study

Objective: The aim of this retrospective study was to compare surgical and survival outcome in only patients with early-stage UCSs managed by laparotomic surgery (LPT) versus minimally invasive surgery (MIS). Methods: Data were retrospectively collected in four Italian different institutions. Inclusion criteria were UCS diagnosis confirmed by the definitive histological examination, and stage I or II according to the FIGO staging system. Results: Between August 2000 and March 2019, the data relative to 170 patients bearing UCSs were collected: of these, 95 were defined as early-stage disease (stage I-II) based on the histological report at the primary surgery, and thus were included in this study. Forty-four patients were managed by LPT, and 51 patients were managed by MIS. The operative time was lower in the MIS group versus the LPT group (p value 0.021); the median estimated blood loss was less in the MIS group compared to the median of LPT group (p value &lt; 0.0001). The length of hospital stay days was shorter in the MIS patients (p value &lt; 0.0001). Overall, there were eight (8.4%) post-operative complications; of these, seven were recorded in the LPT group versus one in the MIS group (p value 0.023). There was no difference in the disease-free survival (DFS) and overall survival (OS) between the two groups. Conclusion: There was no difference of oncologic outcome between the two approaches, in face of a more favourable peri-operative and post-operative profile in the MIS group

DARA-VD VERSUS DARA-RD AS SALVAGE THERAPY FOR PATIENTS WITH MYELOMA. INITIAL FOLLOW-UP OF AN ITALIAN MULTICENTER RETROSPECTIVE CLINICAL EXPERIENCE BY RETE EMATOLOGICA PUGLIESE

Background: Daratumumab is a CD38 monoclonal antibody approved in monotherapy or in combination with bortezomib and dexamethasone (Dara-Vd) or lenalidomide and dexamethasone (Dara-Rd) for the treatment of relapsed or refractory myeloma (rrMM). Aims: We report here an initial multicenter retrospective analysis of 126 consecutive patients with rrMM treated with daratumumab in combination with bortezomib or lenalidomide as salvage therapy at 9 haematological centers in Puglia, conducted to evaluate the outcomes, as well as the toxicity profile of these combination in a daily practice setting outside clinical trials. Methods: Of 126 patients, 122 were evaluable for response and toxicity. Forty-two patients (33%) (15 F and 27 M) received Dara-Vd and 84 patients (67%) (41 F and 43 M) with Dara-Rd; 74% of them had relapsed MM and 26% MM refractory to one or more previous treatment lines. The median age at diagnosis was 62 years (range 36-77) in the Vd-group, 66 years (range 32-83) in the Rd-group. The median time to initiation of daratumumab from diagnosis was 5 years (range 3-9) in the Vd-group, 3 years (range 1-10) in the Rd-group. Patients had received a median 2 prior lines of therapy (range 1-6) in the Vd-group, a median 1 prior course of therapy (range 1-4) in the Rd-group. Twenty patients (48%) in the Vd-group and 30 patients (37%) in the Rd-group had previously undergone single or tandem ASCT. In the Vd-group all patients were previously exposed to at least one proteasome inhibitor (91% of patients to bortezomib, 37% of patients to carfilzomib), in the Rd-group only 18% of patients was exposed to lenalidomide. Results: The median number of administered cycles was 9 (range 1-23) in the VD-group and 8.5 (range 1-23) in the Rd-group. The ORR was 68.2% in the Vd-group (CR 4.8%, VGPR 12.2%, PR 51.2%) and 81.5% in the Rd-group (CR 21%, VGPR 35.8%, pr 24.7%). Median TTR was 2 months (range 1-6) in the Vd-group and 1.5 months (range 1-5) in the Rd-group. Median PFS was 10 months (range 8-16; 95% &gt; CI) in the Vd-group; median PFS was not reached in the Rd-group (fig.1). Grade 3/4 neutropenia (37%) was the most common adverse event in the Rd-group, grade 3/4 thrombocytopenia (24%) was the most common adverse event in the Vd-group. Seventeen (41%) patients in the Vd-group discontinued treatment due to relapse, 16 patients (19%) in the Rd-group because of haematological toxicity (4.5%), relapse (7.5%), death (6%) and the development of urological cancer (1%). Summary/Conclusion: A higher rate of ORR (81.5% vs 68.2%) and very good partial response or better (responses &gt; VGPR 56.8% vs 17%) was observed in the Dara-Rd group compared to Dara-Vd group. This difference could be due to the fact that: 1) in the Dara- Rd group the patients had received a lower number of prior antimyeloma therapies compared to Dara-Vd group; 2) the patients in the Dara-Rd group had a more indolent myeloma (median ISS 1) compared to the patients in the Dara-Vd group, who had a more advanced disease (median ISS 3); 3) in the Rd-group only 18% of patients was exposed to lenalidomide, in the Vd-group all patients were previously exposed to at least one proteasome inhibitor. Unfortunately, the interference of daratumumab with immunofixation and serum protein electrophoresis assays may lead to underestimation of CR

Prev Chronic Dis

IntroductionObesity is highly prevalent among American Indians, and effective prevention efforts require caregiver involvement. We examined American Indian (AI) parents' assessment of and level of concern about their kindergarten child's weight status.MethodsWe collected baseline data (fall of 2005 and fall of 2006) on children and their parents or caregivers for a school-based obesity prevention trial (Bright Start) on an AI reservation in South Dakota. The current study uses 413 parent-child pairs. Age- and sex-adjusted body mass index percentiles were categorized as very underweight (<5th percentile), slightly underweight (5th to <15th percentile), normal weight (15th to <85th percentile), overweight (85th to <95th percentile), and obese ( 6595th percentile). Parents or caregivers reported their assessment of and concerns about their child's weight status as well as sociodemographic characteristics. We used mixed-model multivariable analysis to examine associations between sociodemographic characteristics and the probability of parents underclassifying or overclassifying their child's weight status; analyses were adjusted for school as a random effect.ResultsChildren were evenly divided by sex and had a mean age of 5.8 years. Twenty-nine percent of children and 86% of parents were overweight or obese. Approximately 33% (n = 138) of parents underclassified and 7% (n = 29) of parents overclassified their child's weight status. Higher parental weight status and higher concern about their child's weight status increased the probability of underclassification (P for trend = .02 for both).ConclusionIn this sample of at-risk children, one-third of parents underclassified their child's weight status. Childhood obesity prevention programs need to increase awareness and recognition of childhood obesity and address parental weight issues.2012649

Cardiac safety of adjuvant pegylated liposomal doxorubicin with concurrent trastuzumab: a randomized phase II trial

Background The cardiac safety of trastuzumab concurrent with pegylated liposomal doxorubicin (PLD) in an adjuvant breast cancer treatment regimen is unknown. Patients and methods Women with resected node-positive or intermediate-risk node-negative HER2 overexpressing breast cancer and baseline left ventricular ejection fraction (LVEF) ≥55% were randomized (1:2) to doxorubicin 60 mg/m2 (A)+cyclophosphamide 600 mg/m2 (C) every 21 days (q21d) for four cycles or PLD 35 mg/m2+C q21d+trastuzumab 2 mg/kg weekly (H) for 12 weeks. Both groups then received paclitaxel (Taxol, T) 80 mg/m2 with H for 12 weeks followed by H to complete 1 year. The primary end point was cardiac event rate or inability to administer 1 year of trastuzumab. Results Of 181 randomized patients, 179 underwent cardiac analysis. The incidence of cardiac toxicity or inability to administer trastuzumab due to cardiotoxicity was 18.6% [n=11; 95% confidence interval (CI) 9.7% to 30.9%] with A+C → T+H and 4.2% (n=5; 95% CI 1.4% to 9.5%) with PLD+C+H → T+H (P=0.0036). All events, except one, were asymptomatic systolic dysfunction or mildly symptomatic heart failure. Mean absolute LVEF reduction at cycle 8 was greater with doxorubicin (5.6% versus 2.1%; P=0.0014). Conclusion PLD+C+H → T+H is feasible and results in lower early cardiotoxicity rates compared with A+C → T+