Abstract: It is known that combination therapy of tumors allows to obtain a greater effect at lower concentrations used drugs by reducing the side effects induced by higher concentrations of chemotherapeutic agents. In in vitro and in vivo studies have shown that the inhibitor of glycolysis sodium dichloroacetate (DСA) exhibits anticarcinogenic activity, which manifests itself in the inhibition of cell cycle progression and the induction of apoptosis. This wide variation is recorded for therapeutically effective concentrations of the DСА. Previously, we have shown a dose-dependent cytostatic (block G2 / M) and the cytotoxic effect of DCA on carcinoma cells (HeLa G line 63) and the absence of these effects in endothelial cells (ECV 304 line). In this study we evaluated the efficacy of the combined treatment of human cells of HeLa G 63, ECV 304 and HepG2 (hepatoma) by two cytostatic and cytotoxic agents DCA and caffeine sodium benzoate. The purpose of the search for optimal conditions and concentrations of these agents to obtain maximum effect with minimalnocytotoxic concentrations. It has been shown that the 45-hour treatment of cells HeLa G 63 and ECV 304 by 0.7 mM caffeine sodium benzoate did not induce apoptosis (cytometric analysis of the level of sub-G1 population) and did not significantly affect the change in cell cycle progression of HeLa G 63, but in the ECV 304 and HepG2 recorded accumulation in G0 / G1 phases of the cell cycle. HepG2 cell line showed high cytostatic as a (blocking in G0 / G1), and cytotoxicity (apoptosis) sensitivity to caffeine sodium benzoate. Treatment of HepG2 cells with 20 mM DCA was less toxic than caffeine processing and does not lead to blockage of cells in G0 / G1 in comparison with untreated controls. Combined treatment by 0.7mM sodium caffeine benzoate + 20 mM DСA increased almost 6 times the level of apoptosis in HepG2 cells and HeLa G63 in comparison with untreated controls. Wherein in HepG2 cells this is accompanied by increasing accumulation of cells in G0 / G1, and cells HeLa G63 - in G2 / M phases of the cell cycle. Similar processing ECV 304 cells did not induce any cytostatic or cytotoxic effect, confirming earlier findings about its lesser sensitivity to inhibitors of glycolysis. Thus, the combined treatment of these two agents significantly increases their anticarcinogenic efficacy that reduce the dose of the drug and to avoid possible side effects caused by therapeutically effective concentrations of this drugs.
Abstract: Background: Glioblastomas (GBM) are common and aggressive primary brain tumors with an estimated life expectancy of one year. Despite their similarity histopathological they are either primary or secondary, with a difference clinical, biological and prognosis. This explains the survival variable and sometimes prolonged, indicating a difference in their genetic pathways of progression, including genes TP53 and HDI witch play, with other genetic alterations, an important role.
Objective: Studying the frequency of TP53 IDH1 and IDH2 gene mutations, in the primary GBM Moroccan patients and correlate clinical factors, molecular abnormalities, and survival
Materiel and methods: Eigthy nine patients undergoing primary glioblastoma were selected with a clinical and radiological study and molecular analysis in search of TP53 and IDH mutation by PCR and sequencing.
Results: It was a male predominance with 54 males (61.67%) and 35 women, with a sex ratio of 1.5H/1F. The average age was 52.06 ± 5.28 years. Nearly 80% had neurological deficit, 73% had intracranial hypertension and 20% had epilepsy. Karnofski score (KPS) of our patients preoperatively ranged from 20 to 100, with a median 70 (95% CI, 50-90) and 61.8% had a KPS less than 80. The tumor was on the right side in 50 patients (55.88%), with a frontal location in 35.29% and parieto-temporal in 23.5%. The tumor volume calculated according to three dimensions is between 14.14 and 154.68 cm3, with a mean of 58.5 ± 12.71cm3. The resection was total or subtotal in 39% of cases. 71 patients (80%) had received radiotherapy and 21 of our patients had received chemotherapy. Molecular analysis revealed 3 cases of mutation of P53 (8.82%), R273H,
R306X, and Q136X. No IDH1 or IDH2 mutation was found. The median survival was 12 months. The most significant prognostic factors were age less than 60 years (p log- rank test= 0.0088), KPS >80 (P= 0.0002) and radiothérapy (P < 0.0001).
Discussion and conclusion: The low rate of TP53 mutations (8.82%) and none of the IDH in our study is explained by the nature of the primary GBM and the small number of patients studied. It comes out of our study and those of the literature that age, KPS, extension of surgical excision combined with radiation and chemotherapy are the most significant therapeutic and clinical prognosis factors. But it’s difficult to establish a consistent and significant relationship between molecular markers and the evolution of GBM patients. If the prognostic value of TP53 mutation is uncertain, that the IDH is associated with prolonged survival. It is possible after various alterations identification to identify subgroups of GBM, and create targeted therapies.
Abstract: Lrrc24 is a 513 amino acid transmembrane protein with a domain organization very similar to Kekkon-1. Preliminary data from the Fennell lab has revealed that Lrrc24 decreases ErbB receptor expression as efficiently as Lrig1, strongly suggesting that Lrrc24 is a negative regulator of the ErbB family of RTKs. Furthermore, Lrr24 is expressed in the murine mammary gland and the epithelium of the healthy human breast but may be decreased in breast cancer. Analysis of the Weigelt breast cancer dataset demonstrates that Lrrc24 expression inversely correlates with time to metastasis, suggesting that Lrrc24 could be a metastasis suppressor. Furthermore, Lrrc24 is decreased in prostate adenocarcinoma compared to normal prostate. Collectively, our preliminary data highlight several key features of Lrrc24 which suggest it could be an important growth suppressor including its ability to negatively regulate oncogenic ErbB RTKs, its expression in normal tissue in which ErbBs are expressed and its potential loss in cancer. I
hypothesize that Lrrc24 is a novel negative regulator of the ErbB family of RTKs and that it functions to suppress ErbB-driven tumor cell proliferation, motility and/or invasion.
Neuroendocine carcinoma of the gynecologic tract is rare and poses a significant clinical challenge because of tumor heterogeneity and lack of standardized guidelines for treatment.
Ovotestis refers to the histology of a gonad that contains both ovarian follicles and testicular tubular elements. ovotesticular disorder of sexual development occurs in fewer than 10% of all disorders of sexual development. Gonadal tumors with malignant potential occur in 2.6% of all cases of ovotesticular disorder of sexual development.
Here we represent a 77-year-old woman with primary amenorrhea, infertility and 10cm solid mass in left adnex with 46 XY in karyotype with ovotestis neuroendocrine neoplasm in pathology report which was treated with a multi-modality manner including surgery and chemotherapy but she came back with pulmonary metastasis after 2 cycles of chemotherapy.
Neuroendocrine carcinoma of the ovary is a rare and aggressive tumor commonly associated with other surface epithelial and germ cell neoplasms. The prevalence of ovotestis is rare and gonadal malignancies are the most reported neoplasm affected the ovotestis.
Biography: Tarangi Sutaria is a fourth-year medical student at Virginia Tech Carilion School of Medicine. She completed her undergraduate studies at The Ohio State University, where she majored in Biomedical Science and minored in Public Health. Tarangi’s journey into medicine is marked by service to her community through AmeriCorps and extracurricular initiatives. She is a member of the Gold Humanism Honor Society and Omicron Delta Kappa National Leadership Honor Society. Tarangi intends to enter the field of Obstetrics and Gynecology as an intern this July.
Abstract: Current recommendations for lung cancer screening based on the National Lung Screening Trial (NLST) call for annual chest computed tomography scans (CCT) for high-risk patients [1,2,3]. These recommendations are not widely accepted by physicians and healthcare organizations given controversy surrounding the high false-positive rate associated with the screening modality and broad definition of high-risk patients (number needed to screen = 320) [4,5,6,7]. We seek to understand whether the recommended high-risk lung cancer screening population can be narrowed to patients with even higher risk of developing lung cancer to create more targeted screening criteria.
This study is a retrospective review of Carilion Clinic’s electronic medical records (EMR) of patients between ages 50-80 years with a ≥30 pack-year history for smoking cigarettes, who received a CCT during an ED visit between January 2010 and March 2016. Statistical analysis involved a two-sample test of proportions to test the primary hypothesis and multiple logistic regression analysis to test the secondary hypothesis by assessing the relationship between the explanatory variables of gender, age, and comorbidities (i.e., chronic obstructive pulmonary disorder, hypertension, hyperlipidemia, coronary artery disease, peripheral vascular disease, congestive heart failure, type 2 diabetes mellitus, and history of non-lung cancer).
There is a significant difference in proportions of abnormal lung nodules detected in the Carilion ED population compared to the initially screened NLST subjects (Z = 7.96, p < 0.0001). The only parameters that increase the likelihood of a subject presenting with an abnormal lung nodule are the comorbidities of having a history of non-lung cancer (χ2 = 9.151, p = 0.0025) and a history of chronic obstructive pulmonary disease (COPD) (χ2 = 5.781, p = 0.0162). In conclusion, patients who receive a CCT during an ED visit have a higher proportion of abnormal lung nodules found on imaging than the comparable NLST subjects, and patients with a prior history of extrapulmonary cancers and/or COPD have a higher likelihood of presenting with an abnormal lung nodule ≥4mm in size on CCT than those without these comorbidities
Abstract: The polyamines, spermidine (Spd) and spermine (Spm) are essential in all eukaryotic cells. Ornithine decarboxylase (ODC) is the key enzyme of polyamine (PA) biosynthesis. Increased PA biosynthesis is a well-known promoter of carcinogenesis. Mutations in ODC is a hallmark of several cancer types. The rate of ODC degradation and inhibition of PA uptake is regulated by a small regulatory protein, antizyme (OAZ).
Difluoromethylornithine (DFMO), an irreversible inhibitor of ODC, is in clinical use against African sleeping sickness. It is very effective cytostatic agent in vitro, but its clinical efficacy has been limited by the compensatory increase of the uptake of extracellular PAs into tumor tissue.
Triethylenetetramine (TETA) is a charge-deficient isosteric analog of Spd and efficient Copper chelator, used as a drug for Wilson’s disease. Also preclinical in vivo and in vitro studies show that TETA may be a promising anticancer agent. In our study we tested the anticancer efficacy of TETA alone and in combination with DFMO.
TETA markedly inhibited cell growth, suppressed polyamine uptake, and completely prevented DFMO-induced increase in polyamine uptake in DU145 cells. The suppression of growth was attributed to its ability to induce antizyme, decrease ODC activity, and prevent polyamine uptake. The same results was obtained in the animal experiments. Thus, TETA-DFMO represents a promising combination anticancer therapy.
Abstract: Specific genetic mutations in HPV16DNA are considered important in cervical lesion progression. This study analyzes to what extent radiotherapy treatment contributes to viral DNA variation in cervical cell carcinomas, and the biological significance of these variations.
Serial tumor tissue, including 44 cervical cancer samples, collected before and after radiotherapy, and 52 biopsies with normal cervices, were tested and analyzed for the presence of HPV16, and for the integrity of the E2 gene. Analysis was performed with polymerase chain reaction (PCR), and a bidirectional sequencing assay was performed to find HPV16E2 gene variants.
HPV16E2 accounted for 81.8% and 37.5% among tumor and benign cervices respectively (P<0.05). The incremental number of DNA variations was associated with radiotherapy treatment. Most E2 gene variations involved regions encoding the amino-terminal and carboxy-terminal regions of E2 in the tumor irradiated samples. Amino acid changes T135K, A143T, N203D and P208A in the amino-terminal region were the most common variations across the irradiated samples. Rather, the variations in the carboxy-terminal region (T3694A and T3805G) were synonymous changes. Specific nucleotide deletions were detected in the hinge domain, at positions 3455A>-, 3466 T>-, and 3501A>-. The mutation degree is influenced by the irradiation modalities, interestingly E2 sequence variation being found widely after radiotherapy treatment with a total fractioned dose of 50 Gy (P<0.01).
E2 variation has predictive and biological significance in cervical cancer patients receiving curative radiation therapy. Possibly, E2 variation could influence viral genome intactness and could serve as an intrinsic marker for cervical cancer.
Biography: Dr Ella is a fourth-year Bachelor Student in Computer Science. She is interested in Research Experience in field of Medical Informatics and Intelligent Systems. Since 2014, she has a study in breast cancer sphere. Their team build a mathematical model and whole natural history for primary tumor and the secondary distant metastases in 2015, which was discussed on several conferences in Russia, and for primary tumor and primary metastases in 2016. Also, both models were implemented in software tool. They are working on a new mathematical model and whole natural history for primary tumor and secondary distant metastases growth in patients with lymph nodes metastases.
Abstract: This study considers the problem of mathematical modelling of the progression and stages of breast cancer. We propose a new mathematical growth model for primary tumor and primary metastases which may help to improve predicting accuracy of breast cancer progression using an original mathematical model referred to CoM-IV and corresponding software. We are interested in: 1) modelling the whole natural history of primary tumor and primary metastases; 2) developing adequate and precise CoM-IV which reflects relations between primary tumor and metastases; 3) analyzing the CoM-IV scope of application; 4) implementing the model as a software tool.
The proposed model is based on exponential tumor growth model and performs a system of determinate nonlinear and linear equations; corresponds to TNM classification. It allows to calculate different growth periods of primary tumor and primary metastases: 1) "non-visible period" for primary tumor; 2) "non-visible period" for primary metastases; 3) "visible period" for primary metastases. The new predictive tool: 1) is a solid foundation to develop future studies of breast cancer models; 2) does not require any expensive diagnostic tests; 3) is the first predictor which makes forecast using only current patient data, the others are based on the additional statistical data.
Thus, the CoM-IV model and predictive software: a) detect different growth periods of primary tumor and primary metastases; b) make forecast of the period of primary metastases appearance; c) have higher average prediction accuracy than other tools; d) can improve forecasts on survival of BC and facilitate optimization of diagnostic tests. The following are calculated by CoM-IV: the number of doublings for «non-visible» and «visible» growth period of primary metastases; tumor volume doubling time (days) for «non-visible» and «visible» growth period of primary metastases. The CoM-IV enables, for the first time, to predict the whole natural history of primary tumor and primary metastases growth on each stage (pT1, pT2, pT3, pT4) relying only on primary tumor sizes. Summarizing: a) CoM-IV describes correctly primary tumor and primary distant metastases growth of IV (T1-4N0-3M1) stage with (N1-3) or without regional metastases in lymph nodes (N0); b) facilitates the understanding of the appearance period and inception of primary metastases.
Biography: Sara Paltrinieri is Occupational Therapist graduated at the University of Modena and Reggio Emilia in 2015. She is conducting a post-graduate scholarship focused on work inclusion of people treated for oncologic diseases and through a literature systematic review she is investigating the factors that might affect work retention of people who have been treated for cancer. She is also going to end an epidemiologic survey to know the employment rate and factors impact on RTW of cancer survivors in the territory of Reggio Emilia.
Abstract: Countries with an high development index are experiencing increase in both life expectation and in working age. This features will bring aged people with chronic disease, including cancer, in the workforce. Epidemiologic data show that approximately half of the new diagnosis and more than 1/3 of cancer survivors are people between 15 and 64 years .
Return to work (RTW) is a significant issue in this population because it might help to maintain or restore a satisfactory health status, to preserve social participation and social role, to restore self-perception of own identity and also to increase quality of life. Additionally, RTW has relevant direct negative effects on the social cost supported by Health Services, patients and families. In Italy, the socio-economic influence of loss of productivity due to cancer related consequences, was estimated in more than 8 billions of impact on the employing companies .
Therefore, a review of the factors that might affect work retention of people who have been treated for cancer would seem appropriate.
For this reason, we conducted this systematic review of the literature with the aim to investigate the employment status in European cancer survivors. We also sought to explore the objective and subjective factors that might affect work retention in this population. We search studies published between 2010 and 2015 using MEDLINE, EMBASE, CINAHL, COCHRANE e PsycINFO. We included European population-based studies with employment rate as outcome, measured in adult survivors of any type of cancer.
Ten studies met the inclusion criteria. Employment rate accounted for a minimum of 60% up to a maximum of 84% after an average of 2 years post-diagnosis. Studies were conducted in Northern Europe countries, United Kingdom and France. None of them was conducted in the South of Europe. Socio-demographic factors (i.e. age, gender, level of education, living with a partner, etc..), work-related factors (i.e. type of occupation, work contract, hours worked, average monthly income, etc..) and health-related factors (i.e. tumor type, prognosis, treatment, side effects, etc..) might promote or limit RTW process to a various extent.
RTW is crucial for well-being of a growing population of cancer survivors in their working age. High development index countries should promote interventions sustaining higher rates of employment in this population. These interventions might focus on a wide range of factors associated to RTW. Southern Europe countries should firstly investigate the effects of cancer on employment rate in their contexts.
Biography: Rodrigo Araldi is Biologist, specialist in Viral Oncogenesis, master and Ph.D. student in Biotechnology by University of São Paulo (Brazil), has expertise in mutagenesis and carcinogenesis associated to papillomaviruses, having papers and book published in this theme.
Abstract: The human papillomavirus (HPV) is responsible to 30% of all reported incident infectious agent-associated cancer cases. For this reason, to understand the multiple steps of carcinogenesis is crucial in attempt to reduce the HPV-associated cancer incidence. In this scene, the bovine papillomavirus (BPV) emerges as useful model to study the HPV-related oncogenic process, considering that these viruses share morphological and pathological similarities. Although recognized as mutagenic/carcinogenic, the BPV/HPV action on cell metabolism remains unclear. The lack of studies about the possible interaction between viral infection and cell energy metabolism can be attributed to the rare attention to cell cultures derived from papillomavirus-infected lesions.
Our group has showed that primary cultures derived from BPV-infected lesions are useful model to study the viral biology. In this pioneer report, we describe the study about the metabolism of cells derived from cutaneous papilloma, fibropapilloma and esophageal carcinoma co-infected by BPV-1, 2 and 4. Using the MitoTracker probe (Invitrogen, USA), we verified an increase in mitochondrial membrane potential (Δψm) in benign lesions (papilloma and fibropapilloma) compared to cells derived from BPV-free skin (control). However, esophageal carcinoma cells showed a loss of Δψm, suggesting the activation of glycolytic metabolism (“Warburg effect”). These results were verified by immunofluorescence and flow cytometry. We also analyzed the reactive oxygen species (ROS) levels using the DCFH-DA probe (Sigma, Germany). Results of this analysis showed an increase in ROS production in both papilloma and fibropapilloma cells compared to cells derived from BPV-free skin. Cells derived from esophageal carcinoma showed a reduction of ROS production, reinforcing the activation of glycolytic pathway. Considering that current studies showed the pro-oxidant activity of HPV-16 E6* oncoprotein (a splicing variant of E6), we also analyzed the effects of BPV-1 E6 oncoprotein in cells derived from BPV-free health skin. Results of this analysis showed that BPV-1 E6 oncoprotein induces the loss of Δψm, but increase the ROS production, suggesting that BPV E6 oncoprotein has a pro-oxidant action homologous to HPV-16 E6* oncoprotein.
In conclusion, our results suggest that BPV promotes metabolic deregulation as a consequence of E6-mediated pro-oxidant action. Our results also bring strong evidences that primary cultures derived from BPV/HPV-infected lesions are useful models to study the interaction between viral infection and cell metabolism, as well as to identify novel therapeutic targets, since energy metabolism switch is considered a cancer hallmark.
Abstract: Owing to the high prevalence of gynecological malignancies worldwide, it is of utmost importance to detect these malignancies early, thus reducing their morbidity and mortality rates. Imaging plays a significant role not only in detection but also, owing to the new functional techniques including perfusion MRI, in staging and directing treatment planes. In this article we review the different perfusion techniques used in endometrial, cervical and ovarian malignancies and the importance and potential benefits for their use.
Abstract: Objective: To highlight the clinical association nitric oxide (NO) and Th1/Th2 ratio with immunoglobulins and in patients with newly diagnosed B-cell non-Hodgkin’s lymphoma.
Methods: Thirty four (34) newly diagnosed patients with aggressive B-cell NHL and 25 age-, sex and body mass index (BMI)-matched healthy controls were randomly selected for a cross-sectional case-control study conducted at the Hematology Department of Tlemcen University Medical Centre (Northwest of Algeria).
Results: Circulating levels NO and those of IgA and IgM were significantly higher in patients than in controls. The levels of Th1/Th2 ratio and plasma total antioxidant capacity (ORAC) were significantly lower in patients compared with controls; while malondialdehyde (MDA) and protein carbonyl (PC) levels were significantly higher in patients. B-cell NHL Additionally, the disease was significantly associated with high levels of NO production from 50th to 75th percentile [50th percentile; RR = 2.68, 95% CI 1.55-4.62, p = 0.001, 75th percentile; RR = 7.24, 95% CI 3.18-16.47, p = 0.000]). Moreover, LDL-BCD levels were positively and significantly correlated with IFN-γ; whereas, NO levels were inversely and significantly correlated with IFN-γ and Th1/Th2 ratio.
Conclusions: NO production seem to be associated with aggressive B-cell NHL and alteration of Th1/Th2 ratio. Additionally, the NO appears one of the main mediators that are related to the decreased production of IFN-γ.