22 research outputs found
Valuation of the Aroeira (Myracrodruon urundeuva Allemão): perspectives on conservation
Estrutura e composição de um trecho de Mata Atlântica no Parque Estadual das Fontes do Ipiranga, São Paulo, SP, Brasil
Potential seed dispersal by Didelphis albiventris (Marsupialia, Didelphidae) in highly disturbed environment
Composição florística de florestas estacionais ribeirinhas no estado de Mato Grosso do Sul, Brasil
Primary cervical carcinoma cell lines overexpress epithelial cell adhesion molecule (EpCAM) and are highly sensitive to immunotherapy with MT201, a fully human monoclonal anti-EpCAM antibody
Introduction: Epithelial cell adhesion molecule (EpCAM) is a surface glycoprotein
highly differentially expressed in many epithelial malignancies. The goal of this study was
to evaluate the expression of EpCAM and the potential of MT201 (adecatumumab), a
human monoclonal antibody targeting EpCAM, against multiple primary cervical carcinoma
cell lines.
Methods: Epithelial cell adhesion molecule expression was evaluated by real-time polymerase
chain reaction and flow cytometry in a total of 8 primary cervical cancer cell lines.
Sensitivity to MT201-mediated cellular cytotoxicity (ADCC) and complement-dependent
cytotoxicity was tested in standard 4-hour 51Cr release assays. To investigate the effect of
interleukin-2 (IL-2) on MT201-mediated ADCC, 4-hour 51Cr release assays were also
conducted in the presence of low doses of IL-2.
Results: High messenger RNA expression by real-time polymerase chain reaction and
high EpCAM surface expression by flow cytometry were detected in 4 (50%) of 8 primary
cervical carcinoma cell lines. With no exception, the primary cell lines derived from
clinically aggressive tumors showed EpCAM overexpression. Whereas these cell lines were
highly resistant to complement-dependent cytotoxicity and natural killer (NK)-dependent
cytotoxicity in vitro (range of killing, 4%Y19%), EpCAM-positive cell lines showed high
sensitivity to MT201-mediated ADCC (range of killing, 23%Y59%). Incubation with IL-2 in
addition to MT201 significantly increased the cytotoxic activity against EpCAM-positive
cervical cancer cell lines (P = 0.007). Addition of human serum also further increased the
MT201-mediated killing of EpCAM-positive cell lines (P = 0.03).
Conclusions: Epithelial cell adhesion molecule is highly expressed in primary cervical
carcinoma cell lines, and these biologically aggressive tumors are highly sensitive to
MT201-mediated cytotoxicity in vitro. MT201 may represent a novel, potentially highly
effective treatment option for patients with cervical carcinoma, especially for those with
advanced, recurrent, or metastatic disease refractory to standard salvage therapy
Evaluation of treatment effects in patients with endometrial cancer and POLE mutations: An individual patient data meta-analysis
BACKGROUND Endometrial cancers (ECs) with somatic mutations in DNA polymerase epsilon (POLE) are characterized by unfavorable pathological features, which prompt adjuvant treatment. Paradoxically, women with POLE-mutated EC have outstanding clinical outcomes, and this raises concerns of overtreatment. The authors investigated whether favorable outcomes were independent of treatment. METHODS A PubMed search for POLE and endometrial was restricted to articles published between March 1, 2012, and March 1, 2018, that provided individual patient data (IPD), adjuvant treatment, and survival. Following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) reporting guidelines for IPD, the authors used univariate and multivariate one-stage meta-analyses with mixed effects Cox models (random effects for study cohorts) to infer the associations of treatment, traditional prognostic factors, and outcome, which was defined as the time from first diagnosis to any adverse event (progression/recurrence or death from EC). RESULTS Three hundred fifty-nine women with POLE-mutated EC were identified; 294 (82%) had pathogenic mutations. Worse outcomes were demonstrated in patients with nonpathogenic POLE mutations (hazard ratio, 3.42; 95% confidence interval, 1.47-7.58; log-rank P < .01). Except for stage (P < .01), traditional prognosticators were not associated with progression/recurrence or death from disease. Adverse events were rare (11 progressions/recurrences and 3 disease-specific deaths). Salvage rates in patients who experienced recurrence were high and sustained, with 8 of 11 alive without evidence of disease (range, 5.5-14.2 years). Adjuvant treatment was not associated with outcome. CONCLUSIONS Clinical outcomes for ECs with pathogenic POLE mutations are not associated with most traditional risk parameters, and patients do not appear to benefit from adjuvant therapy. The observed low rates of recurrence/progression and the high and sustained salvage rates raise the possibility of safely de-escalating treatment for these patients. LAY SUMMARY Ten percent of all endometrial cancers have mutations in the DNA repair gene DNA polymerase epsilon (POLE). Women who have endometrial cancers with true POLE mutations experience almost no recurrences or deaths from their cancer even when their tumors appear to have very unfavorable characteristics. Additional therapy (radiation and chemotherapy) does not appear to improve outcomes for women with POLE-mutated endometrial cancer, and this supports the move to less therapy and less associated toxicity. Diligent classification of endometrial cancers by molecular features provides valuable information to inform prognosis and to direct treatment/no treatment.Molecular tumour pathology - and tumour geneticsMTG8 - Moleculaire pathologie van gynecologische tumore
The use of scaning electron microscopy in postvaccinal evaluation of tracheal epithelium of Coturnix coturnix japonica
Evaluation of treatment effects in patients with endometrial cancer and POLE mutations: An individual patient data meta-analysis
BACKGROUND Endometrial cancers (ECs) with somatic mutations in DNA polymerase epsilon (POLE) are characterized by unfavorable pathological features, which prompt adjuvant treatment. Paradoxically, women with POLE-mutated EC have outstanding clinical outcomes, and this raises concerns of overtreatment. The authors investigated whether favorable outcomes were independent of treatment.METHODS A PubMed search for POLE and endometrial was restricted to articles published between March 1, 2012, and March 1, 2018, that provided individual patient data (IPD), adjuvant treatment, and survival. Following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) reporting guidelines for IPD, the authors used univariate and multivariate one-stage meta-analyses with mixed effects Cox models (random effects for study cohorts) to infer the associations of treatment, traditional prognostic factors, and outcome, which was defined as the time from first diagnosis to any adverse event (progression/recurrence or death from EC).RESULTS Three hundred fifty-nine women with POLE-mutated EC were identified; 294 (82%) had pathogenic mutations. Worse outcomes were demonstrated in patients with nonpathogenic POLE mutations (hazard ratio, 3.42; 95% confidence interval, 1.47-7.58; log-rank P < .01). Except for stage (P < .01), traditional prognosticators were not associated with progression/recurrence or death from disease. Adverse events were rare (11 progressions/recurrences and 3 disease-specific deaths). Salvage rates in patients who experienced recurrence were high and sustained, with 8 of 11 alive without evidence of disease (range, 5.5-14.2 years). Adjuvant treatment was not associated with outcome.CONCLUSIONS Clinical outcomes for ECs with pathogenic POLE mutations are not associated with most traditional risk parameters, and patients do not appear to benefit from adjuvant therapy. The observed low rates of recurrence/progression and the high and sustained salvage rates raise the possibility of safely de-escalating treatment for these patients.LAY SUMMARYTen percent of all endometrial cancers have mutations in the DNA repair gene DNA polymerase epsilon (POLE).Women who have endometrial cancers with true POLE mutations experience almost no recurrences or deaths from their cancer even when their tumors appear to have very unfavorable characteristics.Additional therapy (radiation and chemotherapy) does not appear to improve outcomes for women with POLE-mutated endometrial cancer, and this supports the move to less therapy and less associated toxicity.Diligent classification of endometrial cancers by molecular features provides valuable information to inform prognosis and to direct treatment/no treatment