Pub Date : 2017-06-13DOI: 10.4172/2324-9110.1000E110
C. Schmidt, Mark A. Brown
Relating the Pendulum of Democracy with Oncology Research Abstract It has been over 40 years since President Richard M. Nixon signed the National Cancer Act. Considered radically progressive by some in 1971, few today recognize the political implications of this legislation for a conservative U.S. president. In retrospect, the signing of the National Cancer Act highlights how closely most U.S. politicians operate to political center, relative to their global counterparts. Thus, the rest of the world is often mystified by the ability of the pendulum of American democracy to drive revolutionary events with global impacts, following a subtle swing to the left or right of the political center. Herein, we reflect upon the relationship between this pendulum of democracy and oncology research.
{"title":"Will PD-1/PD-L1 Inhibitor Become a True Salvage Therapy for Relapsed or Refractory Patients with Hematological Malignancies?","authors":"C. Schmidt, Mark A. Brown","doi":"10.4172/2324-9110.1000E110","DOIUrl":"https://doi.org/10.4172/2324-9110.1000E110","url":null,"abstract":"Relating the Pendulum of Democracy with Oncology Research \u0000Abstract \u0000It has been over 40 years since President Richard M. Nixon signed the National Cancer Act. Considered radically progressive by some in 1971, few today recognize the political implications of this legislation for a conservative U.S. president. In retrospect, the signing of the National Cancer Act highlights how closely most U.S. politicians operate to political center, relative to their global counterparts. Thus, the rest of the world is often mystified by the ability of the pendulum of American democracy to drive revolutionary events with global impacts, following a subtle swing to the left or right of the political center. Herein, we reflect upon the relationship between this pendulum of democracy and oncology research.","PeriodicalId":73658,"journal":{"name":"Journal of clinical & experimental oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41465391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective: Although great success has been achieved in cancer treatment, current cancer therapies, including anti-tumorigenesis and anti-angiogenesis, still face the problems of insufficient efficacy, resistance and intrinsic refractoriness, in addition to their toxic side effects. There is a demand to identify additional targets that can be blocked to turn off the downstream effects of most, if not all, pathways. Our previous studies suggest that orphan nuclear receptor TR3 (human) / Nur77 (mouse) is such a target. However, the correlation of TR3 expression and clinical tumor progression has not been studied.
Methods: The expression of TR3 was analysed in human primary hepatic cancer specimens from patients that have complete medical records with Immunohistochemical staining. The statistical analysis was used to assess the significance of TR3 expression in tumor tissues, paratumor tissues and normal tissues, and to investigate the correlation of TR3 expression and clincopathologic characteristics.
Results: TR3 is highly expressed in human hepatic cancer tissues, but not in normal liver tissues. The positive expression yields of TR3 are 67.67% (14/21), 19.05% (4/21) and 0% (0/10) in cancer tissues, para cancer tissues, and normal liver tissue, respectively, which are statistic significant (χ2=17.07, p<0.005). The expression of TR3 is significantly higher in cancer tissues than in para cancer tissues χ2=9.722, p<0.005) and in normal tissues (p<0.0005). The levels of TR3 expression in human hepatic cancer tissues correlates well with tumors that are at low/middle degree of tumor differentiation and have portal vein thrombosis, metastasis and recurrence, but not with age, gender, tumor number and Alpha-fetal protein (AFP) volume.
Conclusion: The results indicate that TR3 is a specific therapeutic target for hepatic cancers.
{"title":"Orphan Nuclear Receptor TR3/Nur77 is a Specific Therapeutic Target for Hepatic Cancers.","authors":"Yingling Zeng, Xiaoguang Ye, Degui Liao, Shizhang Huang, Huinan Mao, Dezheng Zhao, Huiyan Zeng","doi":"10.4172/2324-9110.1000184","DOIUrl":"https://doi.org/10.4172/2324-9110.1000184","url":null,"abstract":"<p><strong>Objective: </strong>Although great success has been achieved in cancer treatment, current cancer therapies, including anti-tumorigenesis and anti-angiogenesis, still face the problems of insufficient efficacy, resistance and intrinsic refractoriness, in addition to their toxic side effects. There is a demand to identify additional targets that can be blocked to turn off the downstream effects of most, if not all, pathways. Our previous studies suggest that orphan nuclear receptor TR3 (human) / Nur77 (mouse) is such a target. However, the correlation of TR3 expression and clinical tumor progression has not been studied.</p><p><strong>Methods: </strong>The expression of TR3 was analysed in human primary hepatic cancer specimens from patients that have complete medical records with Immunohistochemical staining. The statistical analysis was used to assess the significance of TR3 expression in tumor tissues, paratumor tissues and normal tissues, and to investigate the correlation of TR3 expression and clincopathologic characteristics.</p><p><strong>Results: </strong>TR3 is highly expressed in human hepatic cancer tissues, but not in normal liver tissues. The positive expression yields of TR3 are 67.67% (14/21), 19.05% (4/21) and 0% (0/10) in cancer tissues, para cancer tissues, and normal liver tissue, respectively, which are statistic significant (χ2=17.07, p<0.005). The expression of TR3 is significantly higher in cancer tissues than in para cancer tissues χ2=9.722, p<0.005) and in normal tissues (p<0.0005). The levels of TR3 expression in human hepatic cancer tissues correlates well with tumors that are at low/middle degree of tumor differentiation and have portal vein thrombosis, metastasis and recurrence, but not with age, gender, tumor number and Alpha-fetal protein (AFP) volume.</p><p><strong>Conclusion: </strong>The results indicate that TR3 is a specific therapeutic target for hepatic cancers.</p>","PeriodicalId":73658,"journal":{"name":"Journal of clinical & experimental oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5548139/pdf/nihms887901.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35311166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-05-30DOI: 10.4172/2324-9110.1000185
B. Yashaswini, A. Mutahar, B. Salimath
Objective: Anti-angiogenesis and pro-apoptosis are the two processes which are strategically used to target tumors. The soluble form of VEGF receptor 1 (Flt-1) is a modulator of VEGF activity and could be useful as a trap to intrinsically sequester VEGF in tumor cells. In the present study, we have investigated the role of rTRAIL in inhibiting VEGF-mediated angiogenesis and its synergistic potentiation by sFlt-1. Methods: We have expressed human recombinant TRAIL, to study its role in anti-angiogenesis and a 2-domain active variant of sFlt-1 by bacterial expression to be used as a trap for VEGF. 3[H] thymidine incorporation assay was used to confirm the inhibitory activity of sFlt-1 and/or rTRAIL on cell proliferation. The synergistic anti-migratory and anti-angiogenic activity of sFlt-1 and rTRAIL were assessed using endothelial cell wound healing and tube formation assay in-vitro and by rat corneal micropocket assay in-vivo. Results: Inhibition of cell proliferation was evident in sFlt-1 and rTRAIL treated cells in a dose -dependent manner with more than 60% reduction in proliferation rate as compared to the tumor cells treated with sFlt-1 and rTRAIL alone. Furthermore, the anti-metastatic and anti-angiogenic activity of sFlt-1 and rTRAIL in combination was evident in endothelial wound healing and tube formation with a significant reduction in the number of cells migrated into the wounded area and the number of honey comb-like structures with the length of the tubes formed to mimic blood vessel formation in-vitro respectively. The in-vivo corneal micropocket assay confirmed the anti-angiogenic effect of sFlt-1 and rTRAIL in combination. Conclusion: The synergistic role of sFlt-1 and rTRAIL as the potential inhibitors of VEGF- mediated angiogenesis could be therapeutically exploited.
{"title":"Antiangiogenic Activity of rTRAIL is Potentiated by Sflt-1, a VEGF Trap","authors":"B. Yashaswini, A. Mutahar, B. Salimath","doi":"10.4172/2324-9110.1000185","DOIUrl":"https://doi.org/10.4172/2324-9110.1000185","url":null,"abstract":"Objective: Anti-angiogenesis and pro-apoptosis are the two processes which are strategically used to target tumors. The soluble form of VEGF receptor 1 (Flt-1) is a modulator of VEGF activity and could be useful as a trap to intrinsically sequester VEGF in tumor cells. In the present study, we have investigated the role of rTRAIL in inhibiting VEGF-mediated angiogenesis and its synergistic potentiation by sFlt-1. \u0000Methods: We have expressed human recombinant TRAIL, to study its role in anti-angiogenesis and a 2-domain active variant of sFlt-1 by bacterial expression to be used as a trap for VEGF. 3[H] thymidine incorporation assay was used to confirm the inhibitory activity of sFlt-1 and/or rTRAIL on cell proliferation. The synergistic anti-migratory and anti-angiogenic activity of sFlt-1 and rTRAIL were assessed using endothelial cell wound healing and tube formation assay in-vitro and by rat corneal micropocket assay in-vivo. \u0000Results: Inhibition of cell proliferation was evident in sFlt-1 and rTRAIL treated cells in a dose -dependent manner with more than 60% reduction in proliferation rate as compared to the tumor cells treated with sFlt-1 and rTRAIL alone. Furthermore, the anti-metastatic and anti-angiogenic activity of sFlt-1 and rTRAIL in combination was evident in endothelial wound healing and tube formation with a significant reduction in the number of cells migrated into the wounded area and the number of honey comb-like structures with the length of the tubes formed to mimic blood vessel formation in-vitro respectively. The in-vivo corneal micropocket assay confirmed the anti-angiogenic effect of sFlt-1 and rTRAIL in combination. \u0000Conclusion: The synergistic role of sFlt-1 and rTRAIL as the potential inhibitors of VEGF- mediated angiogenesis could be therapeutically exploited.","PeriodicalId":73658,"journal":{"name":"Journal of clinical & experimental oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46335083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-05-26DOI: 10.4172/2324-9110.1000186
Gayatri Devi, A. Badana, M. Ch, P. Muralimohan, Shail, Rakhi P. Naik, I. BhaskarReddy, Seema Kumari, R. Malla
Tetraspnin CD151 is involved in proliferation, motility, and invasion. Yet, the role of CD151 in estrogen receptor positive breast cancer is not reported. In the present study, the role of CD151 in survival of ER positive cell line and the underlying molecular partners was reported. CD151 shRNA expression vector was transfected into MCF-7 cells and its efficacy was evaluated by RT-PCR. The capacity of proliferation, migration, and invasion, cell adhesion, angiogenesis of MCF-7 cells was diminished by the knockdown of CD151 via CD151 specific shRNA. It arrested the cell cycle at G2/M phase and induced the apoptosis. The expressions of c-myc, α3β1 integrin, IL-8, Ras, FAK and VEGF were reduced by knockdown of CD151. The results conclude that CD151 gene silencing affects the expression of its network partner’s associate with survival of MCF-7 cells. Therefore, CD151 may be a potential target of luminal and basal subtypes.
{"title":"Knockdown of CD151 Gene Expression Reduces Survival of Estrogen Receptor Positive Breast Cancer Cells","authors":"Gayatri Devi, A. Badana, M. Ch, P. Muralimohan, Shail, Rakhi P. Naik, I. BhaskarReddy, Seema Kumari, R. Malla","doi":"10.4172/2324-9110.1000186","DOIUrl":"https://doi.org/10.4172/2324-9110.1000186","url":null,"abstract":"Tetraspnin CD151 is involved in proliferation, motility, and invasion. Yet, the role of CD151 in estrogen receptor positive breast cancer is not reported. In the present study, the role of CD151 in survival of ER positive cell line and the underlying molecular partners was reported. CD151 shRNA expression vector was transfected into MCF-7 cells and its efficacy was evaluated by RT-PCR. The capacity of proliferation, migration, and invasion, cell adhesion, angiogenesis of MCF-7 cells was diminished by the knockdown of CD151 via CD151 specific shRNA. It arrested the cell cycle at G2/M phase and induced the apoptosis. The expressions of c-myc, α3β1 integrin, IL-8, Ras, FAK and VEGF were reduced by knockdown of CD151. The results conclude that CD151 gene silencing affects the expression of its network partner’s associate with survival of MCF-7 cells. Therefore, CD151 may be a potential target of luminal and basal subtypes.","PeriodicalId":73658,"journal":{"name":"Journal of clinical & experimental oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42235937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-05-26DOI: 10.4172/2324-9110.1000183
J. Skubis-Zegadło, M. Kowalska, B. Śpiewankiewicz, Wacław Smiert Krzysztof Gawrychowski, M. Małecki
Objective: Recombinant adeno-associated virus (rAAV) type 2 is a common vector used in gene therapy. However, the presence of anti-AAV2 neutralizing antibodies or other neutralizing factors can significantly limit effective transduction. Intraperitoneal gene therapy could enable local delivery of the target gene directly to ovarian cancer cells. Until now, there have been no reports on the presence of anti-AAV antibodies in ascitic fluid, which might limit the effectiveness of rAAV as a candidate vector for intraperitoneal gene therapy. Thus, the characterization of the preexisting neutralization antibodies in ascitic fluid will provide insight into successful intraperitoneal gene therapy. Methods: The study was conducted on 23 ascitic fluid samples obtained from women with stage 3 and 4 ovarian cancer. The samples were collected to determine the presence of anti-AAV antibodies with ELISA test and the presence of neutralizing antibodies with neutralizing assay. Results: Our results indicate that anti-rAAV antibodies are present in 70%, whereas neutralizing factors/antibodies are present in 78% of analyzed ascitic fluid samples. This correlation provides evidence for the presence of additional, different from antibodies, currently unknown factors in ascites, which are able to inhibit AAV2 infection in the absence of anti-AAV antibodies. Conclusion: The presence of neutralizing antibodies against rAAV or other neutralizing factors in ascitic fluid should be taken into account during intraperitoneal gene therapy, because they might limit effective intraperitoneal gene therapy with rAAV as a vector.
{"title":"Anti Adeno-Associated Virus 2 (AAV) Antibody Profile in Ovarian Cancer Ascitic Fluid: Implications for AAV Intraperitoneal Gene Therapy","authors":"J. Skubis-Zegadło, M. Kowalska, B. Śpiewankiewicz, Wacław Smiert Krzysztof Gawrychowski, M. Małecki","doi":"10.4172/2324-9110.1000183","DOIUrl":"https://doi.org/10.4172/2324-9110.1000183","url":null,"abstract":"Objective: Recombinant adeno-associated virus (rAAV) type 2 is a common vector used in gene therapy. However, the presence of anti-AAV2 neutralizing antibodies or other neutralizing factors can significantly limit effective transduction. Intraperitoneal gene therapy could enable local delivery of the target gene directly to ovarian cancer cells. Until now, there have been no reports on the presence of anti-AAV antibodies in ascitic fluid, which might limit the effectiveness of rAAV as a candidate vector for intraperitoneal gene therapy. Thus, the characterization of the preexisting neutralization antibodies in ascitic fluid will provide insight into successful intraperitoneal gene therapy. \u0000Methods: The study was conducted on 23 ascitic fluid samples obtained from women with stage 3 and 4 ovarian cancer. The samples were collected to determine the presence of anti-AAV antibodies with ELISA test and the presence of neutralizing antibodies with neutralizing assay. \u0000Results: Our results indicate that anti-rAAV antibodies are present in 70%, whereas neutralizing factors/antibodies are present in 78% of analyzed ascitic fluid samples. This correlation provides evidence for the presence of additional, different from antibodies, currently unknown factors in ascites, which are able to inhibit AAV2 infection in the absence of anti-AAV antibodies. \u0000Conclusion: The presence of neutralizing antibodies against rAAV or other neutralizing factors in ascitic fluid should be taken into account during intraperitoneal gene therapy, because they might limit effective intraperitoneal gene therapy with rAAV as a vector.","PeriodicalId":73658,"journal":{"name":"Journal of clinical & experimental oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43216732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-03-23DOI: 10.4172/2324-9110.1000177
C. Rodríguez-Cerdeira, Munoz-Garzon
Purpose: Basal cell carcinoma (BCC), the most common type of skin cancer in humans, rarely progresses to locally advanced or metastatic BCC. The size, extent, and location of the lesion should be carefully considered when selecting a treatment option for patients with BCC. Methods: Moreover, clinicians should review the potential for significant deformity and anticipated morbidity, when considering radiation therapy and surgery for treatment. Vismodegib, the first approved oral therapy for advanced BCC, is a treatment option that clinicians might consider for patients with BCC lesions that exhibit the clinical characteristics as described above. Results: In this manuscript, we reviewed the mechanism of action, clinical efficacy, and safety of vismodegib and consider the possible causes for a lack of response to the drug. Conclusion: The therapeutic response to these tumors may be limited by the challenge of acquired resistance against smoothened antagonists.
{"title":"Lack of Response to Vismodegib in a Patient with Advanced Basal Cell Carcinoma: A Case Report","authors":"C. Rodríguez-Cerdeira, Munoz-Garzon","doi":"10.4172/2324-9110.1000177","DOIUrl":"https://doi.org/10.4172/2324-9110.1000177","url":null,"abstract":"Purpose: Basal cell carcinoma (BCC), the most common type of skin cancer in humans, rarely progresses to locally advanced or metastatic BCC. The size, extent, and location of the lesion should be carefully considered when selecting a treatment option for patients with BCC. \u0000Methods: Moreover, clinicians should review the potential for significant deformity and anticipated morbidity, when considering radiation therapy and surgery for treatment. Vismodegib, the first approved oral therapy for advanced BCC, is a treatment option that clinicians might consider for patients with BCC lesions that exhibit the clinical characteristics as described above. \u0000Results: In this manuscript, we reviewed the mechanism of action, clinical efficacy, and safety of vismodegib and consider the possible causes for a lack of response to the drug. \u0000Conclusion: The therapeutic response to these tumors may be limited by the challenge of acquired resistance against smoothened antagonists.","PeriodicalId":73658,"journal":{"name":"Journal of clinical & experimental oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49537326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-03-23DOI: 10.4172/2324-9110.1000182
O. Harb, S. Shorbagy, Nehal S. Abouhashem, O. Elfarargy, S. Balata, L. Gertallah, Mohammed M.N. Abozaid, W. Galal, Sameh Saber
Background: Non-small cell carcinoma of lung (NSCLC) is the commonest and most lethal lung cancer type; it includes squamous cell carcinoma, adenocarcinoma, and large cell carcinoma subtypes. The five-year survival rate in NSCLC patients is still very low although improvements in treatment modalities are still emerging. Hence, new prognostic markers and therapies need to be brought to light aiming to improve patients' outcome. Cripto-1 (CR-1) is one of the family members of epidermal-growth-factor; cripto FRL1 cryptic-(EGF-CFC) is needed for embryogenesis. Runt-related-transcription-factor [RUNX] family members make core-binding factor complex (CBFC) that attach to DNA to stimulate or inhibit many genes transcription, regulate the survival, differentiation and maturation of many tissues. The aim of this work is to detect the clinical significance and prognostic role of CR-1 and RUNX2 expressions in NSCLC using immunohistochemistry. Method: CR-1 and RUNX2 expressions were evaluated in 59 paraffin blocks sections of NSCLC. The relationship between their level of expressions and patient's prognosis was analyzed. Results: CR-1 and RUNX2 were highly expressed in NSCLC patients, 59.3% and 67.8%, respectively. There was a significant positive association between their expressions in NSCLC patients (p=0.015). Both markers were significantly correlated with size, grade, stage, site of the tumor within the lung, malignant (pleural and/or pericardial) effusion, presence of distant metastases, ECOG performance status of the patients (p<0.001) and existence of hepatic metastases (p=0.004). Both markers expressions were significantly correlated with poor response to treatment (p<0.001). After a median follow up of 30 months, mean PFS of NSCLC patients having elevated CR-1 and RUNX2 expressions was shorter (p<0.001). Patients with high RUNX2 expressing have significantly shorter mean OS (p=0.025). High CR-1 expression negatively affected OS but that was not statistically significant (p=0.2). Conclusion: NSCLC patients with elevated CR-1 and RUNX2 expression values had unfavorable prognosis.
{"title":"Cripto-1 and RUNX2 Expressions in Non-small Cell Lung Cancer, their Roles in its Progression and Patients Outcome","authors":"O. Harb, S. Shorbagy, Nehal S. Abouhashem, O. Elfarargy, S. Balata, L. Gertallah, Mohammed M.N. Abozaid, W. Galal, Sameh Saber","doi":"10.4172/2324-9110.1000182","DOIUrl":"https://doi.org/10.4172/2324-9110.1000182","url":null,"abstract":"Background: Non-small cell carcinoma of lung (NSCLC) is the commonest and most lethal lung cancer type; it includes squamous cell carcinoma, adenocarcinoma, and large cell carcinoma subtypes. The five-year survival rate in NSCLC patients is still very low although improvements in treatment modalities are still emerging. Hence, new prognostic markers and therapies need to be brought to light aiming to improve patients' outcome. Cripto-1 (CR-1) is one of the family members of epidermal-growth-factor; cripto FRL1 cryptic-(EGF-CFC) is needed for embryogenesis. Runt-related-transcription-factor [RUNX] family members make core-binding factor complex (CBFC) that attach to DNA to stimulate or inhibit many genes transcription, regulate the survival, differentiation and maturation of many tissues. The aim of this work is to detect the clinical significance and prognostic role of CR-1 and RUNX2 expressions in NSCLC using immunohistochemistry. \u0000Method: CR-1 and RUNX2 expressions were evaluated in 59 paraffin blocks sections of NSCLC. The relationship between their level of expressions and patient's prognosis was analyzed. \u0000Results: CR-1 and RUNX2 were highly expressed in NSCLC patients, 59.3% and 67.8%, respectively. There was a significant positive association between their expressions in NSCLC patients (p=0.015). Both markers were significantly correlated with size, grade, stage, site of the tumor within the lung, malignant (pleural and/or pericardial) effusion, presence of distant metastases, ECOG performance status of the patients (p<0.001) and existence of hepatic metastases (p=0.004). Both markers expressions were significantly correlated with poor response to treatment (p<0.001). After a median follow up of 30 months, mean PFS of NSCLC patients having elevated CR-1 and RUNX2 expressions was shorter (p<0.001). Patients with high RUNX2 expressing have significantly shorter mean OS (p=0.025). High CR-1 expression negatively affected OS but that was not statistically significant (p=0.2). \u0000Conclusion: NSCLC patients with elevated CR-1 and RUNX2 expression values had unfavorable prognosis.","PeriodicalId":73658,"journal":{"name":"Journal of clinical & experimental oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46267735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-03-23DOI: 10.4172/2324-9110.1000180
V. Lyra, K. Palialexis, Chrisostomos Constantos, L. Reppas, E. Brountzos, S. Chatziioannou
A patient with non-alcoholic fatty liver disease (NAFLD) and unresectable small-sized (≤3cm) diffuse liver metastases from adenocarcinoma of the rectosigmoid junction was assessed for treatment with transarterial radioembolization (SIRT). The right hepatic arteriogram demonstrated several hypervascular lesions. However, the planar and the SPECT images of the subsequent right hepatic arterial 99mTc-MAA perfusion scintigraphy, revealed significantly heterogeneous distribution of 99mTc-MAA particles and “hot spots”, not corresponding to lesion-specific sites. The no coincidence of the angiographic and the scintigraphic findings could be possibly influenced by hemodynamic changes, due to the presence of significant NAFLD. Because of the high risk-benefit ratio, the patient was considered to be an inappropriate candidate for SIRT.
{"title":"High Extra-Tumoral 99mTc-Macroaggregated Albumin Accumulation in a Fatty Liver in a Candidate for Transarterial Radioembolization Treatment","authors":"V. Lyra, K. Palialexis, Chrisostomos Constantos, L. Reppas, E. Brountzos, S. Chatziioannou","doi":"10.4172/2324-9110.1000180","DOIUrl":"https://doi.org/10.4172/2324-9110.1000180","url":null,"abstract":"A patient with non-alcoholic fatty liver disease (NAFLD) and unresectable small-sized (≤3cm) diffuse liver metastases from adenocarcinoma of the rectosigmoid junction was assessed for treatment with transarterial radioembolization (SIRT). The right hepatic arteriogram demonstrated several hypervascular lesions. However, the planar and the SPECT images of the subsequent right hepatic arterial 99mTc-MAA perfusion scintigraphy, revealed significantly heterogeneous distribution of 99mTc-MAA particles and “hot spots”, not corresponding to lesion-specific sites. The no coincidence of the angiographic and the scintigraphic findings could be possibly influenced by hemodynamic changes, due to the presence of significant NAFLD. Because of the high risk-benefit ratio, the patient was considered to be an inappropriate candidate for SIRT.","PeriodicalId":73658,"journal":{"name":"Journal of clinical & experimental oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43029831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-03-23DOI: 10.4172/2324-9110.1000181
N. Bautista-López, J. Galipeau, J. Cuerquis, M. Lalu, N. Eliopoulos
Background and Objectives: Matrix metalloproteinase (MMP) -2 and -9 play important roles in the invasion and metastasis of breast cancer, but the mechanism of their regulation is not clearly understood. GM-CSF has been shown to be associated with cancer invasion and metastasis. The goal of our study was to examine the stimulation of GM-CSF/ interleukin 3 (IL-3)/IL-5 receptor common β-chain (βc) and its effects on MMP-2 and -9 regulation in human breast cancer cells. Methods: The constitutive expression of the GM-CSF/IL-3/IL-5 receptor common βc and GM-CSF production were analyzed in BT 549, MCF-7, and MDA-MB 231 human breast cancer cell lines. We studied the effects of recombinant IL-3, IL-5 and GM-CSF on the gene expression and enzyme activity of MMP-2, and -9 in the aforementioned cell lines. The signaling pathway activated by these cytokines, the blocking of this pathway, and the effect on MMP-2 and -9 productions were also assessed. The downregulation of the GM-CSF receptor βc gene (CSF2RB) expression and its response to cytokine stimulation were also studied. Results: We observed that the human breast cancer cell lines BT 549, MCF-7, and MDA-MB 231 constitutively produce GM-CSF and express the GM-CSF/IL-3/IL-5 receptor common βc. When these cell lines were treated with recombinant human (rh) GM-CSF, IL-3, and IL-5, enzyme activity and gene expression of MMP-2, and -9 were increased. Conclusions: Our findings indicate that the activation of the c-Fos – ERK 1/2 signaling pathway upregulates MMP-2 in response to exogenous GM-CSF, IL-3 or IL-5 cytokines. Clinically relevant concentrations of GM-CSF (as low as 10 ng/mL) were sufficient to stimulate MMP-2 and -9. Our results suggest a potential mechanism by which GM-CSF may promote tumor invasion and metastases.
{"title":"Induction of Increased Levels of Matrix Metalloproteinase-2 (MMP-2) and -9 in Human Breast Cancer Cell Lines by Activation of GM-CSF Receptor Bc via C-Fos-ERK 1/2 Signaling","authors":"N. Bautista-López, J. Galipeau, J. Cuerquis, M. Lalu, N. Eliopoulos","doi":"10.4172/2324-9110.1000181","DOIUrl":"https://doi.org/10.4172/2324-9110.1000181","url":null,"abstract":"Background and Objectives: Matrix metalloproteinase (MMP) -2 and -9 play important roles in the invasion and metastasis of breast cancer, but the mechanism of their regulation is not clearly understood. GM-CSF has been shown to be associated with cancer invasion and metastasis. The goal of our study was to examine the stimulation of GM-CSF/ interleukin 3 (IL-3)/IL-5 receptor common β-chain (βc) and its effects on MMP-2 and -9 regulation in human breast cancer cells. \u0000Methods: The constitutive expression of the GM-CSF/IL-3/IL-5 receptor common βc and GM-CSF production were analyzed in BT 549, MCF-7, and MDA-MB 231 human breast cancer cell lines. We studied the effects of recombinant IL-3, IL-5 and GM-CSF on the gene expression and enzyme activity of MMP-2, and -9 in the aforementioned cell lines. The signaling pathway activated by these cytokines, the blocking of this pathway, and the effect on MMP-2 and -9 productions were also assessed. The downregulation of the GM-CSF receptor βc gene (CSF2RB) expression and its response to cytokine stimulation were also studied. \u0000Results: We observed that the human breast cancer cell lines BT 549, MCF-7, and MDA-MB 231 constitutively produce GM-CSF and express the GM-CSF/IL-3/IL-5 receptor common βc. When these cell lines were treated with recombinant human (rh) GM-CSF, IL-3, and IL-5, enzyme activity and gene expression of MMP-2, and -9 were increased. \u0000Conclusions: Our findings indicate that the activation of the c-Fos – ERK 1/2 signaling pathway upregulates MMP-2 in response to exogenous GM-CSF, IL-3 or IL-5 cytokines. Clinically relevant concentrations of GM-CSF (as low as 10 ng/mL) were sufficient to stimulate MMP-2 and -9. Our results suggest a potential mechanism by which GM-CSF may promote tumor invasion and metastases.","PeriodicalId":73658,"journal":{"name":"Journal of clinical & experimental oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45560451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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