S. Aregbesola, B. Famurewa, O. Soyele, A. Komolafe
Lipomas are common benign soft tissue tumors, with 15 to 20% of the cases affecting the head and neck region and 1 to 4% involving the oral cavity. The literature has many reported cases of head and neck lipoma but few comprehensive studies hence, the aim of this study was to review and analyze the clinical and histopathologic features of head and neck lipomas in Nigerians. A fifteen-year retrospective study evaluated thirty-six cases of head and neck lipomas among Nigerians. Head and neck lipomas constituted about one-tenth (9.4%) of the total body lipomas seen over the study period. The peak age incidence was fifth decade of life and most (58.3%) of these patients were older than 40 years. There was male gender predilection with male to female ratio of 1.4:1. The most common site of occurrence was forehead (41.7%), followed by scalp and cheek (16.7% each). Lipomas were seen in two intraoral locations (lip and tongue) and these accounted for 13.9% of the head and neck lipomas and 1.3% of lipomas in the whole body. The average size of the lesion was 3.3 cm. Head and neck lipomas are fairly common among Nigerians who are more than 40 years of age. While the conventional and fibrolipoma were the two histologic variants recorded, complete surgical excision of the lesion offered satisfactory treatment outcome. Key words: Head and neck, lipoma.
{"title":"Head and neck lipomas: A clinicopathologic analysis of 36 cases","authors":"S. Aregbesola, B. Famurewa, O. Soyele, A. Komolafe","doi":"10.5897/JCREO2019.0163","DOIUrl":"https://doi.org/10.5897/JCREO2019.0163","url":null,"abstract":"Lipomas are common benign soft tissue tumors, with 15 to 20% of the cases affecting the head and neck region and 1 to 4% involving the oral cavity. The literature has many reported cases of head and neck lipoma but few comprehensive studies hence, the aim of this study was to review and analyze the clinical and histopathologic features of head and neck lipomas in Nigerians. A fifteen-year retrospective study evaluated thirty-six cases of head and neck lipomas among Nigerians. Head and neck lipomas constituted about one-tenth (9.4%) of the total body lipomas seen over the study period. The peak age incidence was fifth decade of life and most (58.3%) of these patients were older than 40 years. There was male gender predilection with male to female ratio of 1.4:1. The most common site of occurrence was forehead (41.7%), followed by scalp and cheek (16.7% each). Lipomas were seen in two intraoral locations (lip and tongue) and these accounted for 13.9% of the head and neck lipomas and 1.3% of lipomas in the whole body. The average size of the lesion was 3.3 cm. Head and neck lipomas are fairly common among Nigerians who are more than 40 years of age. While the conventional and fibrolipoma were the two histologic variants recorded, complete surgical excision of the lesion offered satisfactory treatment outcome. \u0000 \u0000 Key words: Head and neck, lipoma.","PeriodicalId":22619,"journal":{"name":"The Journal of Cancer Research","volume":"1 1","pages":"1-5"},"PeriodicalIF":0.0,"publicationDate":"2019-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78289083","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}
Fawziya A. R. Ibrahim, S. E. E. Feky, Kadhim K. Kadhim, N. A. E. Moneim, Mohammad Abdel-Rahman Ahmmad, S. Sheweita
The present study aimed to show the correlation between expression of cancer stem cell markers (OCT4 and NANOG) with both clinicopathological features and survival of breast cancer (BC) patients. Methods: The gene expressions of OCT4 and NANOG were quantified using real time polymerase chain reaction, clinicopathological data have been collected from patients' data records and patients were followed-up with a median duration of 110 months. Results: OCT4 (p<0.001), and NANOG (p<0.001) expressions were upregulated in BC tissues compared to adjacent normal tissues. OCT4 and NANOG were associated with poor histological grade (p=0.029, 0.025) and advanced clinical stage (p=0.001, 0.042 respectively). OCT4 alone showed a significant association with lymph nodes involvement (p=0.006), metastasis (p=0.024) and was significantly correlated to patients' age (p=0.009). NANOG also showed a significant positive correlation with ERα and PR receptors expression (p=0.004 and 0.005 respectively). Kaplan–Meier curves disclosed that NANOG (p=0.028, 0.050) positive expression was associated with worse DFS and OS, while OCT4 (p=0.200, 0.205) was correlated with poor DFS and OS but not significant statistically. Univariate analysis using Cox proportional hazards regression model analysis showed that OCT4 (p = 0.002), NANOG (p = 0.021), and ERα status (p = 0.004) had significant predictive values for poor DFS. However, the multivariate analysis did not show that any of them can be used as independent prognostic markers for DSF. Conclusions: From these findings, it may be concluded that the upregulated expressions of OCT4 and NANOG were associated with worse clinical outcome and could be used as predictive markers for poor DFS in BC patients.
{"title":"Gene Expression of OCT4 and NANOG Correlated with Advanced Stage and Worse Survival in Breast Cancer Patients","authors":"Fawziya A. R. Ibrahim, S. E. E. Feky, Kadhim K. Kadhim, N. A. E. Moneim, Mohammad Abdel-Rahman Ahmmad, S. Sheweita","doi":"10.12691/JCRT-7-2-1","DOIUrl":"https://doi.org/10.12691/JCRT-7-2-1","url":null,"abstract":"The present study aimed to show the correlation between expression of cancer stem cell markers (OCT4 and NANOG) with both clinicopathological features and survival of breast cancer (BC) patients. Methods: The gene expressions of OCT4 and NANOG were quantified using real time polymerase chain reaction, clinicopathological data have been collected from patients' data records and patients were followed-up with a median duration of 110 months. Results: OCT4 (p<0.001), and NANOG (p<0.001) expressions were upregulated in BC tissues compared to adjacent normal tissues. OCT4 and NANOG were associated with poor histological grade (p=0.029, 0.025) and advanced clinical stage (p=0.001, 0.042 respectively). OCT4 alone showed a significant association with lymph nodes involvement (p=0.006), metastasis (p=0.024) and was significantly correlated to patients' age (p=0.009). NANOG also showed a significant positive correlation with ERα and PR receptors expression (p=0.004 and 0.005 respectively). Kaplan–Meier curves disclosed that NANOG (p=0.028, 0.050) positive expression was associated with worse DFS and OS, while OCT4 (p=0.200, 0.205) was correlated with poor DFS and OS but not significant statistically. Univariate analysis using Cox proportional hazards regression model analysis showed that OCT4 (p = 0.002), NANOG (p = 0.021), and ERα status (p = 0.004) had significant predictive values for poor DFS. However, the multivariate analysis did not show that any of them can be used as independent prognostic markers for DSF. Conclusions: From these findings, it may be concluded that the upregulated expressions of OCT4 and NANOG were associated with worse clinical outcome and could be used as predictive markers for poor DFS in BC patients.","PeriodicalId":22619,"journal":{"name":"The Journal of Cancer Research","volume":"205 ","pages":"36-43"},"PeriodicalIF":0.0,"publicationDate":"2019-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91452943","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}
Assia Mouslim, Saad Menggad, N. Habti, E. Affar, M. Menggad
Pink red-like pigments of crud extracts produced by Streptomyces coelicoflavus MFB11, MFB20, MFB21, MFB23 and MFB24 strains and variants from two spontaneous mutants (MFB11-V and MFB11-Y) as well as prepared fractions (FA and FB) from MFB21 and MFB24 strain pigments were screened for antiproliferative effect by MTT. Cancer cell targets used in this screening were P3 Mice myeloid cell line and/or U2OS human osteosarcoma cell line. The results showed an important antiproliferative effect of some strain pigments on the two organism cell types. U2OS human osteosarcoma cell line was more sensitive to the pigments and showed different antiproliferative effect profiles compared to results obtained on P3 Mice myeloid cell line. FACs analysis of these antiproliferative effects on U2OS human osteosarcoma cell line exhibited cell cycle phase arrests at G1, G1/S or S. This suspects similar mechanism of cell division arrest in U2OS cell induced by these studied compounds to that induced by the apoptotic prodigiosin who differs to that induced by undecylprodigiosin, daunorubicin or other known anthracycline analogues. Thus, these red-like pigments without antibiotic effect unlike prodiginines and anthracyclines could constitute novel related compounds presenting a strong potential for their contribution in anticancer chemotherapy.
{"title":"Antiproliferative Effect on Cancer Cells of Novel Pink Red-like Pigments and Derivatives Produced by Streptomyces coelicoflavus Strains","authors":"Assia Mouslim, Saad Menggad, N. Habti, E. Affar, M. Menggad","doi":"10.12691/JCRT-7-1-5","DOIUrl":"https://doi.org/10.12691/JCRT-7-1-5","url":null,"abstract":"Pink red-like pigments of crud extracts produced by Streptomyces coelicoflavus MFB11, MFB20, MFB21, MFB23 and MFB24 strains and variants from two spontaneous mutants (MFB11-V and MFB11-Y) as well as prepared fractions (FA and FB) from MFB21 and MFB24 strain pigments were screened for antiproliferative effect by MTT. Cancer cell targets used in this screening were P3 Mice myeloid cell line and/or U2OS human osteosarcoma cell line. The results showed an important antiproliferative effect of some strain pigments on the two organism cell types. U2OS human osteosarcoma cell line was more sensitive to the pigments and showed different antiproliferative effect profiles compared to results obtained on P3 Mice myeloid cell line. FACs analysis of these antiproliferative effects on U2OS human osteosarcoma cell line exhibited cell cycle phase arrests at G1, G1/S or S. This suspects similar mechanism of cell division arrest in U2OS cell induced by these studied compounds to that induced by the apoptotic prodigiosin who differs to that induced by undecylprodigiosin, daunorubicin or other known anthracycline analogues. Thus, these red-like pigments without antibiotic effect unlike prodiginines and anthracyclines could constitute novel related compounds presenting a strong potential for their contribution in anticancer chemotherapy.","PeriodicalId":22619,"journal":{"name":"The Journal of Cancer Research","volume":"12 1","pages":"27-33"},"PeriodicalIF":0.0,"publicationDate":"2019-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74922035","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}
Aisha H. Al-Shehri, Ahmed M. Kabel, M. A. A. Elmaaboud
Curcumin is a natural yellow phenolic compound that is located in many types of herbs, especially Curcuma Lana (Turmeric). It is a natural anti-oxidant and has shown many pharmaceutical activities in the preclinical and clinical studies such as antioxidant, anti-microbial, anti-cancer and anti-alzheimer disease effects. In addition, curcumin was proven to be anti-diabetic, hepatoprotective, neuroprotective and anti-rheumatic and it also protects against thrombosis and myocardial infarction. The major limitation to the use of curcumin in clinical practice is its very low oral bioavailability. Therefore, many technologies have been developed and implemented to overcome this limitation. In this review, we discussed the latest perspectives regarding the design and development of nano-sized systems for the anti-diabetic agent curcumin, including liposomes, polymeric nanoparticles, micro-conjugates, micelles, peptide carriers, solid dispersions, cyclodextrins, emulsions and lipid nanopeptides and their role as a promising hope for cancer therapy.
{"title":"The Nanoformulations of Curcumin for Cancer Therapy: New Perspectives","authors":"Aisha H. Al-Shehri, Ahmed M. Kabel, M. A. A. Elmaaboud","doi":"10.12691/JCRT-7-1-4","DOIUrl":"https://doi.org/10.12691/JCRT-7-1-4","url":null,"abstract":"Curcumin is a natural yellow phenolic compound that is located in many types of herbs, especially Curcuma Lana (Turmeric). It is a natural anti-oxidant and has shown many pharmaceutical activities in the preclinical and clinical studies such as antioxidant, anti-microbial, anti-cancer and anti-alzheimer disease effects. In addition, curcumin was proven to be anti-diabetic, hepatoprotective, neuroprotective and anti-rheumatic and it also protects against thrombosis and myocardial infarction. The major limitation to the use of curcumin in clinical practice is its very low oral bioavailability. Therefore, many technologies have been developed and implemented to overcome this limitation. In this review, we discussed the latest perspectives regarding the design and development of nano-sized systems for the anti-diabetic agent curcumin, including liposomes, polymeric nanoparticles, micro-conjugates, micelles, peptide carriers, solid dispersions, cyclodextrins, emulsions and lipid nanopeptides and their role as a promising hope for cancer therapy.","PeriodicalId":22619,"journal":{"name":"The Journal of Cancer Research","volume":"6 1","pages":"21-26"},"PeriodicalIF":0.0,"publicationDate":"2019-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91061652","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}
Amal A. Alghorabi, Ahmed M. Kabel, M. A. A. Elmaaboud
Doxorubicin (DOX) is one of the anthracycline antibiotics that is used frequently for treatment of various types of malignancies including lung, breast and testicular cancers. DOX reacts with DNA by intercalation and inhibits the synthesis of DNA macromolecular components. Also, it may increase the production of free radicals which may contribute to its cytotoxicity. DOX may cause serious adverse effects including cardiotoxicity, hepatotoxicity and testicular toxicity. So, it has become increasingly important to find pharmacological remedies to protect against these serious adverse effects. This mini-review sheds light on DOX including its history, dynamics, clinical uses and adverse effects.
{"title":"Doxorubicin: Insights into Dynamics, Clinical Uses and Adverse Effects","authors":"Amal A. Alghorabi, Ahmed M. Kabel, M. A. A. Elmaaboud","doi":"10.12691/JCRT-7-1-3","DOIUrl":"https://doi.org/10.12691/JCRT-7-1-3","url":null,"abstract":"Doxorubicin (DOX) is one of the anthracycline antibiotics that is used frequently for treatment of various types of malignancies including lung, breast and testicular cancers. DOX reacts with DNA by intercalation and inhibits the synthesis of DNA macromolecular components. Also, it may increase the production of free radicals which may contribute to its cytotoxicity. DOX may cause serious adverse effects including cardiotoxicity, hepatotoxicity and testicular toxicity. So, it has become increasingly important to find pharmacological remedies to protect against these serious adverse effects. This mini-review sheds light on DOX including its history, dynamics, clinical uses and adverse effects.","PeriodicalId":22619,"journal":{"name":"The Journal of Cancer Research","volume":"14 1","pages":"17-20"},"PeriodicalIF":0.0,"publicationDate":"2019-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82807894","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 : 2019-07-25DOI: 10.12677/WJCR.2019.93013
刘美玲, 洪宏海
{"title":"CARM1 Regulates the Growth of Hepatocellular Carcinoma Cells via Regulation of Bax/Bcl-2 Level and Caspase-3 Activity","authors":"刘美玲, 洪宏海","doi":"10.12677/WJCR.2019.93013","DOIUrl":"https://doi.org/10.12677/WJCR.2019.93013","url":null,"abstract":"","PeriodicalId":22619,"journal":{"name":"The Journal of Cancer Research","volume":"21 1","pages":"90-97"},"PeriodicalIF":0.0,"publicationDate":"2019-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80267502","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}
Rasha S. Abo El Alaa, S. A. Ebeid, N. A. E. Moneim, Sanaa A. El-Benhawy, A. Ahmed
Background: Much of the current literature support, the idea that epithelial to mesenchymal transition (EMT) is the key mechanism by which tumor cells gain invasive and metastatic ability, as EMT enables separation of individual cells from the primary tumor mass as well as promote migration. After undergoing EMT, thereby enabling access to hematogenous or lymphatic routes of dissemination, tumor cells can extravasate into secondary organs and establish micro-metastases. Objective: The main target of this work was to study the relation between expression of Doublecortin-like kinase-1 (DCLK-1) and epithelial to mesenchymal transition markers (E-cadherin, vimentin and transforming growth factor-beta (TGF-β)) in breast cancer patients and assess its role in cancer prognosis. Materials and Methods: This study included 60 breast cancer patients and 40 healthy females as control group. Tumor tissues and adjacent normal breast tissues were collected from patients with breast cancer. A single venous blood sample was collected concurrently from breast cancer patients (Before surgery) and from the control group. Tissue expression of DCLK-1, E-cadherin and vimentin were evaluated in breast cancer tissues and normal breast tissues by real-time reverse transcription polymerase chain reaction (RT-PCR). Serum level of TGF-β was assayed by enzyme linked-immunossorbant assay. Results: According to the results of the present study DCLK-1 is highly expressed in breast cancer tissues compared to normal breast tissues. Overexpression of DCLK-1 was significantly correlated with higher tissues Vimentin expression, increased serum TGF-β and lower tissues E-cadherin expression. Kaplan-Meier survival curves for breast cancer patients revealed that, patients with elevated tissue DCLK-1 and Vimentin expression and higher serum TGF-β were significantly associated with poor prognosis in primary breast cancer patients. However, patients with lower tissue E-Cadherin expression had shorter disease free survival time than patients with higher levels. Conclusion: DCLK-1 was significantly increased in breast cancer tissues in comparison to normal breast tissues and its overexpression was significantly correlated with EMT markers and poor prognosis in breast cancer patients. Further prospective studies using greater numbers of patients are required to confirm our findings.
{"title":"Doublecortin like Kinase-1 is Overexpressed in Breast Cancer Tissues and Correlated with Epithelial-mesenchymal Transition Markers","authors":"Rasha S. Abo El Alaa, S. A. Ebeid, N. A. E. Moneim, Sanaa A. El-Benhawy, A. Ahmed","doi":"10.12691/JCRT-7-1-1","DOIUrl":"https://doi.org/10.12691/JCRT-7-1-1","url":null,"abstract":"Background: Much of the current literature support, the idea that epithelial to mesenchymal transition (EMT) is the key mechanism by which tumor cells gain invasive and metastatic ability, as EMT enables separation of individual cells from the primary tumor mass as well as promote migration. After undergoing EMT, thereby enabling access to hematogenous or lymphatic routes of dissemination, tumor cells can extravasate into secondary organs and establish micro-metastases. Objective: The main target of this work was to study the relation between expression of Doublecortin-like kinase-1 (DCLK-1) and epithelial to mesenchymal transition markers (E-cadherin, vimentin and transforming growth factor-beta (TGF-β)) in breast cancer patients and assess its role in cancer prognosis. Materials and Methods: This study included 60 breast cancer patients and 40 healthy females as control group. Tumor tissues and adjacent normal breast tissues were collected from patients with breast cancer. A single venous blood sample was collected concurrently from breast cancer patients (Before surgery) and from the control group. Tissue expression of DCLK-1, E-cadherin and vimentin were evaluated in breast cancer tissues and normal breast tissues by real-time reverse transcription polymerase chain reaction (RT-PCR). Serum level of TGF-β was assayed by enzyme linked-immunossorbant assay. Results: According to the results of the present study DCLK-1 is highly expressed in breast cancer tissues compared to normal breast tissues. Overexpression of DCLK-1 was significantly correlated with higher tissues Vimentin expression, increased serum TGF-β and lower tissues E-cadherin expression. Kaplan-Meier survival curves for breast cancer patients revealed that, patients with elevated tissue DCLK-1 and Vimentin expression and higher serum TGF-β were significantly associated with poor prognosis in primary breast cancer patients. However, patients with lower tissue E-Cadherin expression had shorter disease free survival time than patients with higher levels. Conclusion: DCLK-1 was significantly increased in breast cancer tissues in comparison to normal breast tissues and its overexpression was significantly correlated with EMT markers and poor prognosis in breast cancer patients. Further prospective studies using greater numbers of patients are required to confirm our findings.","PeriodicalId":22619,"journal":{"name":"The Journal of Cancer Research","volume":"52 1","pages":"1-9"},"PeriodicalIF":0.0,"publicationDate":"2019-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80165697","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}
Chimeric antigen receptor T (CAR-T) cell therapy against solid tumors has shown limited success in clinical trials. Solid tumors with highly immunosuppressive tumor microenvironment limit the anti-tumor efficacy of CAR-T cell therapy. Herein we generated a novel vector that co-express human mesothelin (MSLN)-targeted CAR and secretory human anti-programmed death ligand 1 (PD-L1) antibodies. The anti-PD-L1 antibodies secreted from the transduced T cells were able to block the interaction of PD-1/PD-L1 to overcome PD-L1-mediated immune suppression. The CAR-T cells targeting mesothelin and secreting PD-L1 antibodies enhanced cytolytic activity against MSLN+PD-L1+ tumor cells and increased the production of cytokines IL-2, TNFα, and IFNγ. The CAR-T cells targeting MSLN and secreting PD-L1 antibodies had enhanced anti-tumor efficacy when compared with the MSLN-targeted CAR-T cells in xenograft mouse models of mesothelioma, pancreatic and ovarian cancers. The results of this study demonstrated that the co-expression of PD-L1 antibody enhances the anti-tumor efficacy of CAR-T cell therapy against solid tumors.
{"title":"Co-expression of PD-L1 Antibodies Enhances the Anti-Tumor Efficacy of Chimeric Antigen Receptor T Cells","authors":"Shruti Lal, Guan Wang, Zhoushi Chen, X. Xiang, Chengyu Liang, Xue F. Huang, Si-Yi Chen","doi":"10.35248/2684-1266.19.5.119","DOIUrl":"https://doi.org/10.35248/2684-1266.19.5.119","url":null,"abstract":"Chimeric antigen receptor T (CAR-T) cell therapy against solid tumors has shown limited success in clinical trials. Solid tumors with highly immunosuppressive tumor microenvironment limit the anti-tumor efficacy of CAR-T cell therapy. Herein we generated a novel vector that co-express human mesothelin (MSLN)-targeted CAR and secretory human anti-programmed death ligand 1 (PD-L1) antibodies. The anti-PD-L1 antibodies secreted from the transduced T cells were able to block the interaction of PD-1/PD-L1 to overcome PD-L1-mediated immune suppression. The CAR-T cells targeting mesothelin and secreting PD-L1 antibodies enhanced cytolytic activity against MSLN+PD-L1+ tumor cells and increased the production of cytokines IL-2, TNFα, and IFNγ. The CAR-T cells targeting MSLN and secreting PD-L1 antibodies had enhanced anti-tumor efficacy when compared with the MSLN-targeted CAR-T cells in xenograft mouse models of mesothelioma, pancreatic and ovarian cancers. The results of this study demonstrated that the co-expression of PD-L1 antibody enhances the anti-tumor efficacy of CAR-T cell therapy against solid tumors.","PeriodicalId":22619,"journal":{"name":"The Journal of Cancer Research","volume":"63 1","pages":"1-9"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84332908","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}
AsmaH. Qudayr, Ahmed M. Kabel, M. Abdelmaaboud, Waleed Y. Alghamdi, Amal A. Alghorabi
Colorectal cancer is one of the gastrointestinal malignant tumors that carries relatively poor prognosis. It represents one of the most common cancers in males and the third commonest cancer among females worldwide. Various factors may contribute to the pathogenesis of colorectal cancer such as adenomatous polyps and personal history of chronic inflammatory bowel disease. Early colorectal carcinoma is usually asymptomatic. Bleeding from the rectum is the most common presenting symptom. Intestinal obstruction and distant metastasis are life threatening complications of colorectal carcinoma. Accurate diagnosis is achieved by sampling of areas of the colon suspicious for possible tumor development during colonoscopy or sigmoidoscopy. Lines of treatment include surgery, chemotherapy, radiotherapy and biologic treatment. This review sheds light on colorectal carcinoma regarding its prevalence, etiology, clinical presentation, diagnosis and possible lines of management.
{"title":"Colorectal Cancer: New Perspectives","authors":"AsmaH. Qudayr, Ahmed M. Kabel, M. Abdelmaaboud, Waleed Y. Alghamdi, Amal A. Alghorabi","doi":"10.12691/JCRT-6-3-4","DOIUrl":"https://doi.org/10.12691/JCRT-6-3-4","url":null,"abstract":"Colorectal cancer is one of the gastrointestinal malignant tumors that carries relatively poor prognosis. It represents one of the most common cancers in males and the third commonest cancer among females worldwide. Various factors may contribute to the pathogenesis of colorectal cancer such as adenomatous polyps and personal history of chronic inflammatory bowel disease. Early colorectal carcinoma is usually asymptomatic. Bleeding from the rectum is the most common presenting symptom. Intestinal obstruction and distant metastasis are life threatening complications of colorectal carcinoma. Accurate diagnosis is achieved by sampling of areas of the colon suspicious for possible tumor development during colonoscopy or sigmoidoscopy. Lines of treatment include surgery, chemotherapy, radiotherapy and biologic treatment. This review sheds light on colorectal carcinoma regarding its prevalence, etiology, clinical presentation, diagnosis and possible lines of management.","PeriodicalId":22619,"journal":{"name":"The Journal of Cancer Research","volume":"169 1","pages":"80-83"},"PeriodicalIF":0.0,"publicationDate":"2018-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74882206","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}
A. Khalil, A. Alghadi, Rahaf M. T. Shahen, Jehad W. Elasad, K. Jawasreh
Prostate cancer (PCa) has been associated with endoplasmic reticulum stress (ERS) which activates the inositol requiring protein 1α- X-box binding protein-1 (IREα-XBP-1) pathway. The aim of the study was to investigate the role of this pathway in three human PCa cell lines (LNCaP, PC-3, and DU-145) by evaluating the expression of XBP-1 and glucose-regulated protein 78 (GRP78) genes. The effect of two ERS inducers (Thapsigargin, Tg and tunicamycin, Tm) alone and in combination with an inhibitor of the IRE1α RNase inhibitor (STF-083010) on expression profiling was followed using Quantitative-PCR. In vitro treatment of PCa cells with ERS inducers upregulated expression of XBP-1 gene. STF-083010 inhibited IRE1α-induced splicing of the gene and increased cytotoxicity. Inhibition of IRE1α RNase activity significantly decreased expression of chaperon protein GRP78. The results confirm and extend the concept that selective targeting of IRE1α-XBP-1 pathway might be a novel therapeutic approach that curbs PCa cell progression.
{"title":"Inhibition of the Inositol Requiring Protein 1α- X-Box Binding Protein-1 Pathway as a Promising Therapeutic Target for Human Prostate Cancer","authors":"A. Khalil, A. Alghadi, Rahaf M. T. Shahen, Jehad W. Elasad, K. Jawasreh","doi":"10.12691/JCRT-6-3-3","DOIUrl":"https://doi.org/10.12691/JCRT-6-3-3","url":null,"abstract":"Prostate cancer (PCa) has been associated with endoplasmic reticulum stress (ERS) which activates the inositol requiring protein 1α- X-box binding protein-1 (IREα-XBP-1) pathway. The aim of the study was to investigate the role of this pathway in three human PCa cell lines (LNCaP, PC-3, and DU-145) by evaluating the expression of XBP-1 and glucose-regulated protein 78 (GRP78) genes. The effect of two ERS inducers (Thapsigargin, Tg and tunicamycin, Tm) alone and in combination with an inhibitor of the IRE1α RNase inhibitor (STF-083010) on expression profiling was followed using Quantitative-PCR. In vitro treatment of PCa cells with ERS inducers upregulated expression of XBP-1 gene. STF-083010 inhibited IRE1α-induced splicing of the gene and increased cytotoxicity. Inhibition of IRE1α RNase activity significantly decreased expression of chaperon protein GRP78. The results confirm and extend the concept that selective targeting of IRE1α-XBP-1 pathway might be a novel therapeutic approach that curbs PCa cell progression.","PeriodicalId":22619,"journal":{"name":"The Journal of Cancer Research","volume":"25 1","pages":"74-79"},"PeriodicalIF":0.0,"publicationDate":"2018-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74260486","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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