Pub Date : 2017-11-09DOI: 10.4172/2324-9110.1000206
Mohammad Alam, A. Jerah, J. Ashraf, K. Kumaresan, Z. Eisa, N. Mikhail
Objective: PTEN, a tumor-suppressor gene, located on chromosome 10q23.3, is implicated in various types of cancer including breast cancer. The aim of this study is to investigate the promoter methylation, loss of expression and significance of PTEN gene in breast cancer and to determine the correlation between promoter methylation and gene expression. Methods: Promoter methylation and loss of expression of PTEN gene were analyzed using methylation-specific PCR and immunohistochemical methods respectively. The chi square test is used to correlate the promoter methylation and gene expression with their clincopathologic parameters. Results: We examined 53 breast cancer specimens and 10 normal tissues adjacent to tumor. The results showed a 58.5% promoter methylation in PTEN gene and none in normal tissue. PTEN methylation was observed in advanced stages III-IV (81.8%, 18 of 22, P=0.015) and higher grades G2-G3 (71.4%, 20 of 28, P=0.043) of disease. The correlation of PTEN methylation with clinical stage and tumor grade was found to be statistically significant. Nuclear PTEN expression was detected in 73.6% (39 of 53) cases of breast cancer and in the remaining 26.4% (14 of 53) cases expressional loss was observed. The loss of PTEN expression was observed in all normal tissues (10 of 10). The loss of PTEN expression was significantly correlated with patient’s age (P=0.028) and clinical stage (P = 0.029). The expressional loss was observed in 12 (38.7%) cases among 31 methylation positive cases, whereas among 22 methylation- negative cases, only 2 (9.1%) cases were seen as immunostaining negative with the statistically significant value (P=0.016). Conclusion: Promoter methylation and loss of expression of PTEN gene occur frequently in breast cancer. Our results suggest that PTEN plays an important role in breast carcinogenesis.
{"title":"Promoter Methylation and Loss of Expression of PTEN Gene in Breast Cancer Patients from Saudi Population","authors":"Mohammad Alam, A. Jerah, J. Ashraf, K. Kumaresan, Z. Eisa, N. Mikhail","doi":"10.4172/2324-9110.1000206","DOIUrl":"https://doi.org/10.4172/2324-9110.1000206","url":null,"abstract":"Objective: PTEN, a tumor-suppressor gene, located on chromosome 10q23.3, is implicated in various types of cancer including breast cancer. The aim of this study is to investigate the promoter methylation, loss of expression and significance of PTEN gene in breast cancer and to determine the correlation between promoter methylation and gene expression. \u0000Methods: Promoter methylation and loss of expression of PTEN gene were analyzed using methylation-specific PCR and immunohistochemical methods respectively. The chi square test is used to correlate the promoter methylation and gene expression with their clincopathologic parameters. \u0000Results: We examined 53 breast cancer specimens and 10 normal tissues adjacent to tumor. The results showed a 58.5% promoter methylation in PTEN gene and none in normal tissue. PTEN methylation was observed in advanced stages III-IV (81.8%, 18 of 22, P=0.015) and higher grades G2-G3 (71.4%, 20 of 28, P=0.043) of disease. The correlation of PTEN methylation with clinical stage and tumor grade was found to be statistically significant. Nuclear PTEN expression was detected in 73.6% (39 of 53) cases of breast cancer and in the remaining 26.4% (14 of 53) cases expressional loss was observed. The loss of PTEN expression was observed in all normal tissues (10 of 10). The loss of PTEN expression was significantly correlated with patient’s age (P=0.028) and clinical stage (P = 0.029). The expressional loss was observed in 12 (38.7%) cases among 31 methylation positive cases, whereas among 22 methylation- negative cases, only 2 (9.1%) cases were seen as immunostaining negative with the statistically significant value (P=0.016). \u0000Conclusion: Promoter methylation and loss of expression of PTEN gene occur frequently in breast cancer. Our results suggest that PTEN plays an important role in breast carcinogenesis.","PeriodicalId":73658,"journal":{"name":"Journal of clinical & experimental oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46077460","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 : 2017-11-09DOI: 10.4172/2324-9110.1000205
M. Buchholz, J. Berg, C. Braumann, B. Majchrzak-Stiller, S. Hahn, R. Pfirrmann, W. Uhi, A. Chromik
Background: Since the molecular mechanism of the well-known anti-infective and antineoplastic substance Taurolidine (TRD) is still unknown, we sought to analyze the anti-neoplastic capacity of its main metabolite Taurultam (TAU) in malignant human cell lines derived from pancreatic cancer (AsPC-1, BxPC-3, HPAF II, MiaPaca-2, Panc-1) and colon cancer (SW-480, HT-29 and HCT-116) in vitro. Methods: Cell lines were incubated with TAU or TRD in increasing concentrations for 24h and 48h. Comprehensive analyses were performed to quantify the anti-neoplastic activity of TAU: Analysis of cytotoxicity via MTT-assay, inhibition of proliferation via BrdU and induction of apoptosis and necrosis via FACS-analysis. Furthermore, cell growth was monitored using a real-time cell analyzer. Results: TAU revealed a significant cytotoxic and anti-proliferative effect on all pancreatic and colon cancer cell-lines as well in MTT- and BrdU- assays as in the real-time cell analyzer. Furthermore, FACS analyses were characterized by a significant apoptotic and necrotic response upon stimulation with TAU. In contrast to TRD antineoplastic effects were noticeable lower. Conclusion: It could be demonstrated for the first time, that TAU provides antineoplastic effects operating through mechanisms like its parent compound TRD. However, our results show clearly that TAU is not the only anti-neoplastic active metabolite of TRD. Hence, our data suggest that the efficiency of TRD against cancer cells is rather based on the methylol-containing species released during hydrolysis. These promising results are the first step towards the development of a novel substance combining the high anti-neoplastic capacity of TRD with better molecular properties of TAU, like a higher solubility in aqueous solution.
背景:由于众所周知的抗感染和抗肿瘤物质牛磺酸丁(TRD)的分子机制尚不清楚，我们试图分析其主要代谢物牛磺酸丹(TAU)在胰腺癌(AsPC-1, BxPC-3, HPAF II, MiaPaca-2, Panc-1)和结肠癌(ws -480, HT-29和HCT-116)的恶性人细胞系中的体外抗肿瘤能力。方法:用TAU或TRD分别以增加浓度孵育细胞系24h和48h。综合分析量化TAU的抗肿瘤活性:mtt法分析细胞毒性，BrdU法分析增殖抑制，facs法分析诱导凋亡和坏死。此外，使用实时细胞分析仪监测细胞生长情况。结果:TAU对所有胰腺癌和结肠癌细胞系以及MTT-和BrdU-检测均显示出显著的细胞毒性和抗增殖作用。此外，FACS分析的特点是在TAU刺激下出现明显的凋亡和坏死反应。与TRD相比，抗肿瘤作用明显较低。结论:首次证实TAU的抗肿瘤作用机制与其母体化合物TRD类似。然而，我们的研究结果清楚地表明，TAU并不是TRD的唯一抗肿瘤活性代谢物。因此，我们的数据表明，TRD对抗癌细胞的效率是基于在水解过程中释放的含甲基物质。这些有希望的结果是开发一种新型物质的第一步，它将TRD的高抗肿瘤能力与TAU的更好的分子特性(如在水溶液中的溶解度)结合起来。
{"title":"Single Versus Double Ring Structure: Search for Best Anti-Neoplastic Driver in Colon and Pancreatic Cancer Cells-Taurultam or Taurolidine?","authors":"M. Buchholz, J. Berg, C. Braumann, B. Majchrzak-Stiller, S. Hahn, R. Pfirrmann, W. Uhi, A. Chromik","doi":"10.4172/2324-9110.1000205","DOIUrl":"https://doi.org/10.4172/2324-9110.1000205","url":null,"abstract":"Background: Since the molecular mechanism of the well-known anti-infective and antineoplastic substance Taurolidine (TRD) is still unknown, we sought to analyze the anti-neoplastic capacity of its main metabolite Taurultam (TAU) in malignant human cell lines derived from pancreatic cancer (AsPC-1, BxPC-3, HPAF II, MiaPaca-2, Panc-1) and colon cancer (SW-480, HT-29 and HCT-116) in vitro. \u0000Methods: Cell lines were incubated with TAU or TRD in increasing concentrations for 24h and 48h. Comprehensive analyses were performed to quantify the anti-neoplastic activity of TAU: Analysis of cytotoxicity via MTT-assay, inhibition of proliferation via BrdU and induction of apoptosis and necrosis via FACS-analysis. Furthermore, cell growth was monitored using a real-time cell analyzer. \u0000Results: TAU revealed a significant cytotoxic and anti-proliferative effect on all pancreatic and colon cancer cell-lines as well in MTT- and BrdU- assays as in the real-time cell analyzer. Furthermore, FACS analyses were characterized by a significant apoptotic and necrotic response upon stimulation with TAU. In contrast to TRD antineoplastic effects were noticeable lower. \u0000Conclusion: It could be demonstrated for the first time, that TAU provides antineoplastic effects operating through mechanisms like its parent compound TRD. However, our results show clearly that TAU is not the only anti-neoplastic active metabolite of TRD. Hence, our data suggest that the efficiency of TRD against cancer cells is rather based on the methylol-containing species released during hydrolysis. These promising results are the first step towards the development of a novel substance combining the high anti-neoplastic capacity of TRD with better molecular properties of TAU, like a higher solubility in aqueous solution.","PeriodicalId":73658,"journal":{"name":"Journal of clinical & experimental oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70250002","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 : 2017-11-01DOI: 10.4172/2324-9110.1000201
A. Kushwaha
Objective: Atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) are indeterminate lesions with malignancy incidence of 5-15%. We evaluate the role of thyroid ultrasound in predicting malignancy in Bethesda type III nodules, and thus suggest management guidelines in these nodules. Method: Patient with Bethesda type III nodules were subjected to high resolution ultrasonography of neck. The features analysed while performing US examination are size, site, echogenicity (solid, cystic), margins (circumscribed, micro lobular, irregular), calcification (micro, macro or egg shell) and shape of the lesion. On the basis of ultrasound these nodules were categorized into probably benign or suspicious of malignancy. All these patients were subjected to surgery and final histopathological report were compared with ultrasonography features. Results: The positive predictive value of ultrasonogram in predicting malignancy in Bethesda type-III nodules is 84.2%, while specificity of ultrasonogram is 90.9% and sensitivity in predicting malignancy is 80%. Conclusion: When the USG features are suggestive of benign lesion then a repeat USG guided FNAC may be considered and when the USG features are suggestive of malignant lesion then a repeat FNA is unnecessary and a definitive surgery should be considered.
{"title":"Management of Thyroid Nodules with Atypical Cytology on Fine-Needle Aspiration with Ultra Sonogram","authors":"A. Kushwaha","doi":"10.4172/2324-9110.1000201","DOIUrl":"https://doi.org/10.4172/2324-9110.1000201","url":null,"abstract":"Objective: Atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) are indeterminate lesions with malignancy incidence of 5-15%. We evaluate the role of thyroid ultrasound in predicting malignancy in Bethesda type III nodules, and thus suggest management guidelines in these nodules. \u0000Method: Patient with Bethesda type III nodules were subjected to high resolution ultrasonography of neck. The features analysed while performing US examination are size, site, echogenicity (solid, cystic), margins (circumscribed, micro lobular, irregular), calcification (micro, macro or egg shell) and shape of the lesion. On the basis of ultrasound these nodules were categorized into probably benign or suspicious of malignancy. All these patients were subjected to surgery and final histopathological report were compared with ultrasonography features. \u0000Results: The positive predictive value of ultrasonogram in predicting malignancy in Bethesda type-III nodules is 84.2%, while specificity of ultrasonogram is 90.9% and sensitivity in predicting malignancy is 80%. \u0000Conclusion: When the USG features are suggestive of benign lesion then a repeat USG guided FNAC may be considered and when the USG features are suggestive of malignant lesion then a repeat FNA is unnecessary and a definitive surgery should be considered.","PeriodicalId":73658,"journal":{"name":"Journal of clinical & experimental oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45903166","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 : 2017-11-01DOI: 10.4172/2324-9110.1000202
Á. Kellner, Vasana S Kellner, E. Kollar, M. Egyed
The incidence of autoimmune diseases increasing nowdays. Despite of the development of diagnosis and management of diseases, they remained chronic diseases. The patient’s lifespan expansion requires long-term treatment with harmful agents, such as Metothrexate or other immunosuppressive drugs. The Metothrexate toxicities are based on the duration and cumulative dosing of drug, and the combination with other drugs. Myelosuppression and consequent pancytopenia is the most frequent hematologic toxicity, which occur mostly later during low dose Metothrexate administration. We demonstrate three cases of low dose metothrexate toxicity in older patients with rheumatoid arthritis and psoriasis. All patients were treated with low dose Metothrexate along more than one year continuously. Two old patients with RA and another with psoriasis developed pancytopenia causing severe neutropenia, cutaneous bleeding, and bruising and septic condition. They required intravenous antibiotic therapy, corticosteroids and limited transfusion dependence as a result of low dose methotrexate. We have assessed the possible causes of Metothrexate toxicities and found that all patients used non-steroid anti-inflammatory drugs because of pain and proton-pump inhibitor to avoid development of peptic ulcer. Two patients recovered, another died in septic condition. We would like to drawn attention of haematologists, dermatologists and rheumatologists to the harmful effect of low dose methotrexate in this patient population and emphasize the role of rigorous and consequent hematologic testing to avoid these severe late complications.
{"title":"Is Metothrexate so Harmless in Patients with Autoimmune Disorders","authors":"Á. Kellner, Vasana S Kellner, E. Kollar, M. Egyed","doi":"10.4172/2324-9110.1000202","DOIUrl":"https://doi.org/10.4172/2324-9110.1000202","url":null,"abstract":"The incidence of autoimmune diseases increasing nowdays. Despite of the development of diagnosis and management of diseases, they remained chronic diseases. The patient’s lifespan expansion requires long-term treatment with harmful agents, such as Metothrexate or other immunosuppressive drugs. The Metothrexate toxicities are based on the duration and cumulative dosing of drug, and the combination with other drugs. Myelosuppression and consequent pancytopenia is the most frequent hematologic toxicity, which occur mostly later during low dose Metothrexate administration. We demonstrate three cases of low dose metothrexate toxicity in older patients with rheumatoid arthritis and psoriasis. All patients were treated with low dose Metothrexate along more than one year continuously. Two old patients with RA and another with psoriasis developed pancytopenia causing severe neutropenia, cutaneous bleeding, and bruising and septic condition. They required intravenous antibiotic therapy, corticosteroids and limited transfusion dependence as a result of low dose methotrexate. We have assessed the possible causes of Metothrexate toxicities and found that all patients used non-steroid anti-inflammatory drugs because of pain and proton-pump inhibitor to avoid development of peptic ulcer. Two patients recovered, another died in septic condition. We would like to drawn attention of haematologists, dermatologists and rheumatologists to the harmful effect of low dose methotrexate in this patient population and emphasize the role of rigorous and consequent hematologic testing to avoid these severe late complications.","PeriodicalId":73658,"journal":{"name":"Journal of clinical & experimental oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42385839","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 : 2017-11-01DOI: 10.4172/2324-9110.1000204
M. Liaqat, Lucas Gallindo Costa, T. C. Vasconcelos, P. Lessa, E. C. Lins, L. Santos, F. Nunes
Microwave Imaging (MI) of breast cancer is an emerging non-invasive and non-ionizing technique for breast cancer diagnosis based on microwave radiation backscattered by breast tissues. Usually, MBI explore dielectric properties of breast tissues to increase the imaging contrast between tumor and healthy tissue through an Inverse Image Reconstruction Algorithm. Furthermore, MBI systems could be cost-effectively, compact and recent developments drive them to wearable soon. Even X-ray Mammography is the gold-standard for imaging tumors inside breast; it still is low contrast for early diagnostic, painful and age- and dose-restricted because ionizing radiation. Then, in long-term, our group is motivated to develop MBI technique and cost-effectively wearable systems for in vivo early diagnosis of breast cancer as a complimentary to X-ray Mammography. In short-term, we had been designing our systems by simulations, manufacturing and initial in vitro tests in lab. This work presents initial results of design and simulation of a system based on hard and/or flexible antennas ranging between 0.001 GHz to 3 GHz for in vitro experimentation. In detail, two different shapes (rectangular patch and circular slot) of Micro strip Patch antennas were designed and simulated in FR4, Cotton, Polyester and Pyralux Polyimide (for Flexible antennas) materials. The resonance frequency of antennas depends on permittivity of substrate material and its geometry, so the High Frequency Simulation Software (HFSS) simulated scattering parameters of designed antennas, which were also tested on mimic-phantoms of breast. The simulation of rectangular patch and bow-tie antennas resulted on a like-Gaussian curve of microwave emission / detection peaked at 1.9-2.7 GHz with ~50-90MHz band width.
{"title":"A Feasible Novel Technique for Breast Cancer Imaging Using UWB-Microwave Antennas","authors":"M. Liaqat, Lucas Gallindo Costa, T. C. Vasconcelos, P. Lessa, E. C. Lins, L. Santos, F. Nunes","doi":"10.4172/2324-9110.1000204","DOIUrl":"https://doi.org/10.4172/2324-9110.1000204","url":null,"abstract":"Microwave Imaging (MI) of breast cancer is an emerging non-invasive and non-ionizing technique for breast cancer diagnosis based on microwave radiation backscattered by breast tissues. Usually, MBI explore dielectric properties of breast tissues to increase the imaging contrast between tumor and healthy tissue through an Inverse Image Reconstruction Algorithm. Furthermore, MBI systems could be cost-effectively, compact and recent developments drive them to wearable soon. Even X-ray Mammography is the gold-standard for imaging tumors inside breast; it still is low contrast for early diagnostic, painful and age- and dose-restricted because ionizing radiation. Then, in long-term, our group is motivated to develop MBI technique and cost-effectively wearable systems for in vivo early diagnosis of breast cancer as a complimentary to X-ray Mammography. In short-term, we had been designing our systems by simulations, manufacturing and initial in vitro tests in lab. This work presents initial results of design and simulation of a system based on hard and/or flexible antennas ranging between 0.001 GHz to 3 GHz for in vitro experimentation. In detail, two different shapes (rectangular patch and circular slot) of Micro strip Patch antennas were designed and simulated in FR4, Cotton, Polyester and Pyralux Polyimide (for Flexible antennas) materials. The resonance frequency of antennas depends on permittivity of substrate material and its geometry, so the High Frequency Simulation Software (HFSS) simulated scattering parameters of designed antennas, which were also tested on mimic-phantoms of breast. The simulation of rectangular patch and bow-tie antennas resulted on a like-Gaussian curve of microwave emission / detection peaked at 1.9-2.7 GHz with ~50-90MHz band width.","PeriodicalId":73658,"journal":{"name":"Journal of clinical & experimental oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46017183","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 : 2017-10-17DOI: 10.4172/2324-9110.1000203
S. Patel, N. Hayes, Mariarosaria Esposito
Human epidermal growth factor receptor-2 (HER2/ErbB-2) is a receptor tyrosine kinase involved in cell growth and differentiation and over-expressed in about 15-30% of breast cancers. Trastuzumab is an anti-HER2 monoclonal antibody that has significantly improved survival of patients with early and metastatic breast cancer (BC). However, 65% patients experience primary and secondary resistance. This article explores existing and emerging combination therapy for HER2 positive breast cancer, highlighting the success of trastuzumab in combination with another monoclonal antibody, pertuzumab and small molecule tyrosine kinase inhibitors lapatinib and neratinib. Recent studies have indicated that combination of trastuzumab, pertuzumab and lapatinib increases the 3-year overall survival from 90% to 95% in metastatic BC patients. The EPHOS-B trial has shown a remarkable shrinkage of the tumour when lapatinib is used before surgery and chemotherapy. Despite this success, pertuzumab has just been approved for use in the British National Health Service (NHS) while pertuzuamb, lapatinib and neratinib have been approved for European and American markets for a number of years. Lapatinib and neratinib are not available yet in UK. Strict assessment criteria on cost-benefits might limit the access to these drugs to British cancer patients.
{"title":"Trastuzumab Resistance: What Are We Offering to Breast Cancer Patients?","authors":"S. Patel, N. Hayes, Mariarosaria Esposito","doi":"10.4172/2324-9110.1000203","DOIUrl":"https://doi.org/10.4172/2324-9110.1000203","url":null,"abstract":"Human epidermal growth factor receptor-2 (HER2/ErbB-2) is a receptor tyrosine kinase involved in cell growth and differentiation and over-expressed in about 15-30% of breast cancers. Trastuzumab is an anti-HER2 monoclonal antibody that has significantly improved survival of patients with early and metastatic breast cancer (BC). However, 65% patients experience primary and secondary resistance. This article explores existing and emerging combination therapy for HER2 positive breast cancer, highlighting the success of trastuzumab in combination with another monoclonal antibody, pertuzumab and small molecule tyrosine kinase inhibitors lapatinib and neratinib. Recent studies have indicated that combination of trastuzumab, pertuzumab and lapatinib increases the 3-year overall survival from 90% to 95% in metastatic BC patients. The EPHOS-B trial has shown a remarkable shrinkage of the tumour when lapatinib is used before surgery and chemotherapy. Despite this success, pertuzumab has just been approved for use in the British National Health Service (NHS) while pertuzuamb, lapatinib and neratinib have been approved for European and American markets for a number of years. Lapatinib and neratinib are not available yet in UK. Strict assessment criteria on cost-benefits might limit the access to these drugs to British cancer patients.","PeriodicalId":73658,"journal":{"name":"Journal of clinical & experimental oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43017179","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 : 2017-10-04DOI: 10.4172/2324-9110.1000197
Yongqiang Chen, S. Gibson
Selectively inducing cancer cells to death is the goal of cancer therapy. The discovery of B-cell lymphoma 2 (Bcl-2) family members regulating apoptotic cell death of cancer cells revealed new targets for cancer therapy. Bcl-2 family members can be classified into pro-apoptotic members and anti-apoptotic members among which myeloid cell leukemia 1 (Mcl-1) plays unique roles in regulating cell death and survival in cancer cells. Mcl-1 has a short half-life due to its degradation by multiple E3 ubiquitin-ligases. Under hypoxic conditions, Mcl-1 is up-regulated by activation of growth factor receptor, EGFR promoting cell survival whereas, prolonged/severe hypoxia leads to deactivation of EGFR and Mcl-1 degradation by E3 ubiquitin -ligase FBW7 contributing to cell death. Furthermore, cancer cells upregulated Mcl-1 contributing resistance to chemotherapeutic treatment such as by inhibitors of other antiapoptotic Bcl-2 members Bcl-2, Bcl-xL and Bcl-w. Therefore, Mcl- 1 might be the key player in pro-survival Bcl-2 family members in regulating cancer cell death. This encourages the on-going active development of Mcl-1 specific inhibitors for cancer treatment.
{"title":"Mcl-1 is a Gate Keeper Regulating Cell Death in Cancer Cells","authors":"Yongqiang Chen, S. Gibson","doi":"10.4172/2324-9110.1000197","DOIUrl":"https://doi.org/10.4172/2324-9110.1000197","url":null,"abstract":"Selectively inducing cancer cells to death is the goal of cancer therapy. The discovery of B-cell lymphoma 2 (Bcl-2) family members regulating apoptotic cell death of cancer cells revealed new targets for cancer therapy. Bcl-2 family members can be classified into pro-apoptotic members and anti-apoptotic members among which myeloid cell leukemia 1 (Mcl-1) plays unique roles in regulating cell death and survival in cancer cells. Mcl-1 has a short half-life due to its degradation by multiple E3 ubiquitin-ligases. Under hypoxic conditions, Mcl-1 is up-regulated by activation of growth factor receptor, EGFR promoting cell survival whereas, prolonged/severe hypoxia leads to deactivation of EGFR and Mcl-1 degradation by E3 ubiquitin -ligase FBW7 contributing to cell death. Furthermore, cancer cells upregulated Mcl-1 contributing resistance to chemotherapeutic treatment such as by inhibitors of other antiapoptotic Bcl-2 members Bcl-2, Bcl-xL and Bcl-w. Therefore, Mcl- 1 might be the key player in pro-survival Bcl-2 family members in regulating cancer cell death. This encourages the on-going active development of Mcl-1 specific inhibitors for cancer treatment.","PeriodicalId":73658,"journal":{"name":"Journal of clinical & experimental oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45975877","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 : 2017-10-04DOI: 10.4172/2324-9110.1000194
Yusra Kassim, E. Tawil, C. Buquet, D. Cerf, Jean PierreVannier
Besides tumor cells, the microenvironment harbors a variety of host-derived cells. To date, the most successful tissue engineering approaches have employed methods that recapitulate the composition, architecture and/or chemical presentation of the native microenvironment. Thus tumor engineering in biomimetic three dimensional conditions represents a dynamic cooperatively between different cell types in a spatially and functionally accurate fashion. Evidence has been provided that the cross-talk between tumor cells and stromal cells leads to enhanced tumor growth, metastasis and altered response to chemotherapeutic agents. It has been provided that endothelial cells play an important role in tumor in shaping the tumor microenvironment and controlling tumor development, in particular through neo-angiogenesis. We developed a 3D in vitro tumor model that encompasses a cross-linked hyaluronic acid hydrogel providing a physiologically relevant microenvironment for mammary tumor cell and endothelial cell co-culture. We investigated the morphological cross-talk between tumor and endothelial cells in a 3D configuration. Additionally, we observed the influence of co-culturing on the proliferation, angiogenic protein expression and secretion. We demonstrated that endothelial cells tend to acquire a spheroidal configuration with the mammary tumor cells surrounding the endothelial spheroid. We also observed that the levels of VEGF, MMP-2 and MMP-9 have tendencies to decrease within the first 6 days of co-culture, and tend to increase at day 12. This could be due to the restored polarity of the mammary tumor cells leading to a period of quiescence required to restore the malignant organization. These data confirm the importance of tissue architecture and polarity in malignant progression.
{"title":"Three Dimensional Tumor Engineering by Co-Culture of Breast Tumor and Endothelial Cells Using a Hyaluronic Acid Hydrogel Model","authors":"Yusra Kassim, E. Tawil, C. Buquet, D. Cerf, Jean PierreVannier","doi":"10.4172/2324-9110.1000194","DOIUrl":"https://doi.org/10.4172/2324-9110.1000194","url":null,"abstract":"Besides tumor cells, the microenvironment harbors a variety of host-derived cells. To date, the most successful tissue engineering approaches have employed methods that recapitulate the composition, architecture and/or chemical presentation of the native microenvironment. Thus tumor engineering in biomimetic three dimensional conditions represents a dynamic cooperatively between different cell types in a spatially and functionally accurate fashion. Evidence has been provided that the cross-talk between tumor cells and stromal cells leads to enhanced tumor growth, metastasis and altered response to chemotherapeutic agents. It has been provided that endothelial cells play an important role in tumor in shaping the tumor microenvironment and controlling tumor development, in particular through neo-angiogenesis. We developed a 3D in vitro tumor model that encompasses a cross-linked hyaluronic acid hydrogel providing a physiologically relevant microenvironment for mammary tumor cell and endothelial cell co-culture. We investigated the morphological cross-talk between tumor and endothelial cells in a 3D configuration. Additionally, we observed the influence of co-culturing on the proliferation, angiogenic protein expression and secretion. We demonstrated that endothelial cells tend to acquire a spheroidal configuration with the mammary tumor cells surrounding the endothelial spheroid. We also observed that the levels of VEGF, MMP-2 and MMP-9 have tendencies to decrease within the first 6 days of co-culture, and tend to increase at day 12. This could be due to the restored polarity of the mammary tumor cells leading to a period of quiescence required to restore the malignant organization. These data confirm the importance of tissue architecture and polarity in malignant progression.","PeriodicalId":73658,"journal":{"name":"Journal of clinical & experimental oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42596094","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 : 2017-10-04DOI: 10.4172/2324-9110.1000193
C. Anyanechi, B. Saheeb
Background: Odontogenic Myxoma (OM) affects the jaws, and is characterized by high recurrence rate after treatment. Objective: To evaluate the clinical characteristics and treatment outcome of OM that presented in our center. Materials and Methods: A 22-year retrospective study was performed at the Dental and Maxillofacial Surgery Clinic of the study institution; patients’ data were collected from the hospital records and entered into a pro-forma questionnaire. Results: Overall, 643 patients with oro-facial lesions were evaluated and 38/643 (5.9%) were diagnosed with OM. There were 22 (57.8%) males and 16 (42.2%) females with male to female ratio of 1.4:1. Majority (n=30, 78.9%) of the patients were between 21-40 years (p=0.001). Patients presented late and this increased with decreased socio-economic status (p=0.001), whereas the higher the socio-economic status, the smaller were the sizes of the tumor (p=0.001). Majority 33 (86.8%) occurred in the mandible and the tumors were centrally located in the jaws. The longer the duration of tumor, the more the presenting clinical symptoms (p=0.001). Radiologically, 32 (84.2%) cases showed multi-locular radiolucency. The tumors were treated by wide excision, and the greater the sizes of the surgical defects, the more the co-morbidities (p= 0.001). Post-operatively, 10.5% patients had recurrence of the tumor whereas 5.3% spontaneous bone regeneration (SBR). Conclusion: The clinical characteristics and treatment outcome of OM observed is similar to previous reports except that males were affected more than females. Late presentation is the main challenging factor in the early diagnosis and management of this tumor in our environment.
{"title":"The Clinical Presentation of Odontogenic Myxoma of the Jaws: A 22-Year Retrospective Analysis","authors":"C. Anyanechi, B. Saheeb","doi":"10.4172/2324-9110.1000193","DOIUrl":"https://doi.org/10.4172/2324-9110.1000193","url":null,"abstract":"Background: Odontogenic Myxoma (OM) affects the jaws, and is characterized by high recurrence rate after treatment. Objective: To evaluate the clinical characteristics and treatment outcome of OM that presented in our center. \u0000Materials and Methods: A 22-year retrospective study was performed at the Dental and Maxillofacial Surgery Clinic of the study institution; patients’ data were collected from the hospital records and entered into a pro-forma questionnaire. \u0000Results: Overall, 643 patients with oro-facial lesions were evaluated and 38/643 (5.9%) were diagnosed with OM. There were 22 (57.8%) males and 16 (42.2%) females with male to female ratio of 1.4:1. Majority (n=30, 78.9%) of the patients were between 21-40 years (p=0.001). Patients presented late and this increased with decreased socio-economic status (p=0.001), whereas the higher the socio-economic status, the smaller were the sizes of the tumor (p=0.001). Majority 33 (86.8%) occurred in the mandible and the tumors were centrally located in the jaws. The longer the duration of tumor, the more the presenting clinical symptoms (p=0.001). Radiologically, 32 (84.2%) cases showed multi-locular radiolucency. The tumors were treated by wide excision, and the greater the sizes of the surgical defects, the more the co-morbidities (p= 0.001). Post-operatively, 10.5% patients had recurrence of the tumor whereas 5.3% spontaneous bone regeneration (SBR). \u0000Conclusion: The clinical characteristics and treatment outcome of OM observed is similar to previous reports except that males were affected more than females. Late presentation is the main challenging factor in the early diagnosis and management of this tumor in our environment.","PeriodicalId":73658,"journal":{"name":"Journal of clinical & experimental oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49296432","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 : 2017-10-04DOI: 10.4172/2324-9110.1000198
A. Yordanov, B. Dimitrova, M. Karcheva, P. Vasileva, S. Slavchev
Objective: Lymphoepithelioma-like carcinoma of the uterine cervix is a rare subtype of squamous cell carcinoma (SSC) and it is more common in Asia-5.5%, than in Europe-0.7%. It is considered that LELC is associated with Epstein-Barr virus (EBV) infection in Asian and with Human papilloma virus (HPV) or no infection in Caucasian patients. Compared to the common cervical cancer LELC affects younger women, its outcome is better and it has to be with a lower frequency of regional lymph node metastasis and recurrence. Case report: We present three cases of LELC with lymph node metastasis and a follow- up of the patients. The diagnosis was confirmed histologically. All three cases have been examined Immunohistochemically for assessment of the viral status for both EBV and HPV. Two of them died from the cervical cancer and one is still alive without evidence of recurrence. The results of the immunohistochemical study showed that two of them were negative for both viruses and one was positive only for EBV. Conclusion: Our data shows that the immunohistochemical results for the viral status cannot be used as a predictive factor as opposed to the lymph node status and lymphovascular space invasion (LVSI).
{"title":"Lymphoepithelioma-Like Carcinoma of the Uterine Cervix - Reporting Three Rare Clinical Cases with Lymph Node Metastasis","authors":"A. Yordanov, B. Dimitrova, M. Karcheva, P. Vasileva, S. Slavchev","doi":"10.4172/2324-9110.1000198","DOIUrl":"https://doi.org/10.4172/2324-9110.1000198","url":null,"abstract":"Objective: Lymphoepithelioma-like carcinoma of the uterine cervix is a rare subtype of squamous cell carcinoma (SSC) and it is more common in Asia-5.5%, than in Europe-0.7%. It is considered that LELC is associated with Epstein-Barr virus (EBV) infection in Asian and with Human papilloma virus (HPV) or no infection in Caucasian patients. Compared to the common cervical cancer LELC affects younger women, its outcome is better and it has to be with a lower frequency of regional lymph node metastasis and recurrence. \u0000Case report: We present three cases of LELC with lymph node metastasis and a follow- up of the patients. The diagnosis was confirmed histologically. All three cases have been examined Immunohistochemically for assessment of the viral status for both EBV and HPV. Two of them died from the cervical cancer and one is still alive without evidence of recurrence. The results of the immunohistochemical study showed that two of them were negative for both viruses and one was positive only for EBV. \u0000Conclusion: Our data shows that the immunohistochemical results for the viral status cannot be used as a predictive factor as opposed to the lymph node status and lymphovascular space invasion (LVSI).","PeriodicalId":73658,"journal":{"name":"Journal of clinical & experimental oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43675790","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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