In Vitro and In Vivo Efficacy of a Stroma-Targeted, Tumor Microenvironment Responsive Oncolytic Adenovirus in Different Preclinical Models of Cancer.

More than one million women are diagnosed annually worldwide with a gynecological cancer. Most gynecological cancers are diagnosed at a late stage, either because a lack of symptoms, such as in ovarian cancer or limited accessibility to primary prevention in low-resource countries, such as in cervical cancer. Here, we extend the studies of AR2011, a stroma-targeted and tumor microenvironment responsive oncolytic adenovirus (OAdV), whose replication is driven by a triple hybrid promoter. We show that AR2011 was able to replicate and lyse in vitro fresh explants obtained from human ovarian cancer, uterine cancer, and cervical cancer. AR2011 was also able to strongly inhibit the in vitro growth of ovarian malignant cells obtained from human ascites fluid. The virus could synergize in vitro with cisplatin even on ascites-derived cells obtained from patients heavily pretreated with neoadjuvant chemotherapy. AR2011(h404), a dual transcriptionally targeted derived virus armed with hCD40L and h41BBL under the regulation of the hTERT promoter, showed a strong efficacy in vivo both on subcutaneous and intraperitoneally established human ovarian cancer in nude mice. Preliminary studies in an immunocompetent murine tumor model showed that AR2011(m404) expressing the murine cytokines was able to induce an abscopal effect. The present studies suggest that AR2011(h404) is a likely candidate as a novel medicine for intraperitoneal disseminated ovarian cancer.

Oncolytic Adenovirus-Loaded Menstrual Blood Stem Cells Overcome the Blockade of Viral Activity Exerted by Ovarian Cancer Ascites.

Patients with ovarian cancer present peritoneal ascites at recurrence as a marker of disseminated disease and dismal prognosis. Oncolytic immunotherapy is an emerging approach for the treatment of disseminated cancer. In the present work, we constructed a novel oncolytic adenovirus, AR2011, to target malignant ovarian tumors. AR2011 exhibited a clear lytic effect in vitro in human ovarian cancer cell lines and malignant cells obtained from ascitic fluids (AFs) of patients with ovarian cancer. AR2011 activity was neutralized by antibodies present in 31 samples of patient-derived AFs. However, this blockade was overridden by preloading menstrual blood stem cells (MenSCs) with AR2011 (MenSC-AR), since AFs exerted no in vitro inhibitory effect on viral lytic activity under these conditions. Moreover, soluble factors present in AFs act as MenSC chemoattractants. MenSC-AR treatment of nude mice carrying established peritoneal carcinomatosis following administration of human ovarian cancer cells was able to inhibit tumor growth at levels similar to those observed with AR2011 alone. This study demonstrates that MenSCs can be used to override the blockade that AFs exert on viral oncolytic effects.

Further evaluation of the EORTC QLQ-C30 psychometric properties in a large Brazilian cancer patient cohort as a function of their educational status.

PURPOSE: The European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) is considered a valid instrument for use in Brazil. However, the previous Brazilian validation study included only 30 lung cancer patients and only measured test-retest reliability. The aim of this study was to evaluate the psychometric properties of the EORTC QLQ-C30 in a sample of cancer patients at different educational levels who completed the instrument administered by an interviewer. METHODS: Data from six prospective studies conducted by the same group of researchers were combined in this study (N = 986). RESULTS: Reliability was assessed using Cronbach's alpha coefficient, all values of which were >0.7, with the exception of cognitive functioning, social functioning, and nausea and vomiting (α = 0.57, α = 0.69, and α = 0.68, respectively). In multi-trait scaling analysis, convergent and divergent validity were considered adequate (validity indices were 91.6 and 97.4%). In general, moderate to strong correlations were found between the subscales of the EORTC QLQ-C30 and its respective dimensions from the WHOQOL-bref, the hospital anxiety and depression scale, and the Edmonton Symptom Assessment System (ESAS) instruments. In addition, the EORTC QLQ-C30 was able to differentiate groups of patients with distinct performance statuses and types of treatment (known-group validation). Statistical analyses were also performed on educational status, yielding similar results. CONCLUSIONS: Detailed psychometric property data using the EORTC QLQ-C30 in Brazil are added by this study. In addition, we demonstrated that this instrument is in general reliable and valid regardless of the patient educational level.

Biologically based therapies are commonly self-prescribed by Brazilian women for the treatment of advanced breast cancer or its symptoms.

PURPOSE: Breast cancer (BC) might be associated with loss of function in affected patients, with a direct impact on their quality of life (QOL). Many women with metastatic BC seek relief of symptoms, including the use of complementary and alternative medicine (CAM) to cure cancer. The present study aimed to identify the pattern of CAM used by patients with metastatic BC and to assess the correlation between CAM use and scores on anxiety, depression, and QOL scales. METHODS: A total of 126 women with metastatic BC were interviewed using four instruments: (1) a questionnaire containing socioeconomic, clinical, and demographic data and CAM use; (2) European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ)-C30; (3) EORTC QLQ-BR23; and (4) the Hospital Anxiety and Depression Scale. RESULTS: Fifty percent of the participants reported the use of at least one CAM modality. Biologically based practices were the most frequently used to treat BC and/or its symptoms, the most commonly discussed with the oncologists, and one of the CAM categories in which more patients reported a desire to learn more about. The overall use of CAM was not correlated with the scores on the anxiety, depression, and QOL scales. However, analysis of the association of the QOL scores with specific CAM modalities revealed some potential associations (especially for food supplements, art therapy, psychotherapy, and prayer). CONCLUSIONS: Women with metastatic BC frequently make use of CAM to treat the cancer and/or its symptoms. Biologically based practices seem to be particularly important in Brazil. An association between specific CAM modalities and some QOL domains was suggested, but it needs further confirmation.