Gastric cancer is a multifactorial neoplastic pathology numbering among its causes both environmental and genetic predisposing factors. It is mainly diffused in South America and South-East Asia, where it shows the hi...Gastric cancer is a multifactorial neoplastic pathology numbering among its causes both environmental and genetic predisposing factors. It is mainly diffused in South America and South-East Asia, where it shows the highest morbility percentages and it is relatively scarcely diffused in Western countries and North America. Although molecular mechanisms leading to gastric cancer development are only partially known, three main causes are well characterized: Helicobacter pylori(H. pylori) infection, diet rich in salted and/or smoked food and red meat, and epithelial cadherin(E-cadherin) mutations. Unhealthy diet and H. pylori infection are able to induce in stomach cancer cells genotypic and phenotypic transformation, but their effects may be crossed by a diet rich in vegetables and fresh fruits. Various authors have recently focused their attention on the importance of a well balanced diet, suggesting a necessary dietary education starting from childhood. A constant surveillance will be necessary in people carrying E-cadherin mutations, since they are highly prone in developing gastric cancer, also within the inner stomach layers. Above all in the United States, several carriers decided to undergo a gastrectomy, preferring changing their lifestyle than living with the awareness of the development of a possible gastric cancer. This kind of choice is strictly personal, hence a decisioncannot be suggested within the clinical management. Here we summarize the key points of gastric cancer prevention analyzing possible strategies referred to the different predisposing factors. We will discuss about the effects of diet, H. pylori infection and E-cadherin mutations and how each of them can be handled.展开更多
AIM The purpose of this study was to evaluate the diagnostic value of trefoil factor family 3(TFF3) for the early detection of colorectal cancer(CC). METHODS Serum TFF3 and carcino-embryonic antigen(CEA) were detected...AIM The purpose of this study was to evaluate the diagnostic value of trefoil factor family 3(TFF3) for the early detection of colorectal cancer(CC). METHODS Serum TFF3 and carcino-embryonic antigen(CEA) were detected in 527 individuals, including 115 healthy control(HC), 198 colorectal adenoma(CA), and 214 CC individuals in the training group. RESULTS Serum TFF3 showed no significant correlation with age, gender, or tumor location but showed significant correlation with the tumor stage. Serum TFF3 in the CC group was significantly higher than in the HC or CA group. The AUC values of TFF3 for discriminating between HC and CC and between CA and CC were 0.930(0.903, 0.958) and 0.834(0.796, 0.873). A multivariate model combining TFF3 and CEA was built. Compared to TFF3 or CEA alone, the multivariate model showed significant improvement(P < 0.001). For discriminating between HC and CC, HC and early stage CC, HC and advanced stage CC, CA and CC, CA and early stage CC, and CA and advanced stage CC in the training group, the sensitivities were 92.99%, 91.46%, 93.18%, 73.83%, 76.83%, and 81.82%, and the specificities were 91.30%, 91.30%, 93.91%, 88.38%, 77.27%, and 88.38%, respectively. After validation, the sensitivities were 89.39%, 85.71%, 90.79%, 72.73%, 71.43%, and 78.95%, and the specificities were 87.85%, 87.85%, 2.52%, 87.85%, 80.77%, and 87.50%, respectively. CONCLUSION The multivariate diagnostic model that included TFF3 and CEA showed significant improvement over the conventional biomarker CEA and might provide a potential method for the early detection of CC.展开更多
AIM： We optimized a rapid and efficient tissue lysis method using the MagNA Lyser （Roche, Germany）. Using this novel method combined with immunoblot analysis, we investigated the correlation between abnormal Bcl-XL...AIM： We optimized a rapid and efficient tissue lysis method using the MagNA Lyser （Roche, Germany）. Using this novel method combined with immunoblot analysis, we investigated the correlation between abnormal Bcl-XL expression and clinicopathological characteristics in colorectal cancer. METHODS： Tissue samples from Sprague-Dawley rats were tested to determine optimal lysis conditions for use with MagNA Lyser. We next used the new method to extract tissue proteins from the tumor tissue of a colorectal cancer patient. The availability of extractable tissue proteins for proteomic study was demonstrated by two-dimensional （2D） gel electrophoresis and subsequent matrix-assisted laser desorption/ionization time-of-flight （MALDI-TOF） mass spectrometry. In addition, we prepared tissue lysates from paired tumor tissues and adjacent nontumor tissues of 50 colorectal carcinoma patients. Ensuing immunoblot analyses were performed to detect the level of Bcl-X, expression. RESULTS： The optimal sample sizes processed were found to be around 200 mg, with oscillation frequency of 6 500 r/rain for 80 s. Test of the first human tissue lysate confirmed that the MagNA Lyser method was adequate for protein extraction and subsequent identification by current proteomic protocols. The method was also applicable to immunoblot analysis. Thirty of 50 （60%） colorectal patients exhibited higher level of Bcl-XL expression in their tumor tissues. Raised level of Bcl-XL expression correlated with patients＇ gender and tumor cell proliferation index （P= 0.037 and P〈0.001, respectively）, but was independent of clinicopathological characteristics and overall survival. CONCLUSION： We report a novel tissue lysis method applicable to proteomic and immunoblot analyses, which can facilitate the discovery and detection of cancer protein alterations.展开更多
Objective: Targeting mutated EGFR by EGFR-tyrosine kinase inhibitors (EGFR-TKI) is a potent approach to a subset of non-small cell lung cancer (NSCLC). However, the response to EGFR-TKI varies in individual cases even...Objective: Targeting mutated EGFR by EGFR-tyrosine kinase inhibitors (EGFR-TKI) is a potent approach to a subset of non-small cell lung cancer (NSCLC). However, the response to EGFR-TKI varies in individual cases even among tumors carrying the same?EGFR?mutation, suggesting the involvement of modifying factors. To characterize possible modifiers, we examined mutation state of the?EGFR?and the?KRAS?genes in Japanese NSCLC and compared them with the methylation state of lung tumor suppressors, the?CADM1 and?4.1B,?whose products have potentials to modify the functions of EGFR or KRAS. Materials and methods: A total of 103 Japanese NSCLC and 11 NSCLC cell lines were examined. Genomic DNA of exons 18–21 of the?EGFR?and exons 1 and 2 of the?KRAS?were amplified by polymerase chain reaction (PCR), followed by single-strand conformation polymorphism analysis and direct sequencing. Methylation status of gene promoters in NSCLC cells were examined by methylation-specific PCR. Results: Mutations of the?EGFR?and?KRAS?were detected mutually exclusively in 27 and 11 out of 103 NSCLC cases, respectively.?EGFR?mutations were observed exclusively in adenocarcinoma (27 of 69, 41%) and preferentially in tumors from female and non-smokers (p < 0.00001). Eight (30%) and 12 (44%) of 27 tumors carrying mutated?EGFR?and 4 (36%) and 8 (73%) of 11 tumors carrying mutated?KRAS?showed methylation of the?CADM1 and 4.1B, respectively.?EGFR-mutated tumors with methylation of either?CADM1 or 4.1B?showed more malignant features than those with unmethylated?CADM1 and 4.1B?(p < 0.05). Conclusion: Methylation state of the?CADM1 and?4.1B?are independent of the mutation status of the?EGFR?or?KRAS?but play roles in the malignant progression of NSCLC. Integration of epigenetic information would be useful for identifying possible modifiers to predict the response or recurrence of lung adenocarcinoma to the EGFR-TKI therapy.展开更多
Prostate cancer is a common malignant tumor in men,which seriously endangers men's health.At present,in the treatment of prostate cancer in different stages,the survival of patients shows differences,and the survi...Prostate cancer is a common malignant tumor in men,which seriously endangers men's health.At present,in the treatment of prostate cancer in different stages,the survival of patients shows differences,and the survival rate of early prostate cancer is high.The prognosis is good,the survival rate of advanced prostate cancer is low,and the prognosis is poor.Digital rectal examination combined with serum PSA detection is currently recognized as the best method for early prostate cancer screening.However,the specificity of PSA is poor,and a large number of prostate cancer patients are overdiagnosed and overtreated.At the same time,the treatment of advanced prostate cancer also needs more reliable biomarkers to judge the treatment effect and assist clinical decision-making.展开更多
Interleukin-11 （IL-11） is a cytokine of IL-6 family that mediates signal transduction through a common signal transduction molecule glycoprotein 130gp130. JAK/STAT, Ras/Erk and PI3K-mediated pathways are involved in...Interleukin-11 （IL-11） is a cytokine of IL-6 family that mediates signal transduction through a common signal transduction molecule glycoprotein 130gp130. JAK/STAT, Ras/Erk and PI3K-mediated pathways are involved in the IL-11 signaling pathway. IL-11 has traditionally been thought to be an anti-inflammatory cytokine that has a complex role in the body＇s immune response. Simultaneously, the activation of STAT3 by IL-11 provides a functional link to support the survival and growth of cancer cells. There is also evidence that IL-11 may play a role in promoting liver cancer through wound healing mechanisms. In recent years, studies have found that IL-11 could stimulate the development of tumors via promoting the proliferation and inhibiting the apoptosis of cancer cells, mediating the tolerance of cancer cells to radiotherapy and chemotherapy, and mediating the growth and survival of early microtransferred colonies. Sustained activation of JAK-STAT and PI3K-AKT signaling pathway, up-regulating the expression of IL-11 receptor and hypoxia microenvironment mediated by HIF-1a and AP-1 transcription factors are involved in the progression of cancer. Therefore, targeted therapies that treat the over expression of IL-11 or IL-11 receptors and IL-11 signaling pathway such as the JAK 1/2 and STAT3 inhibitor in cancer patients has the potential to completely relieve the tumor, which may provide us a new idea for the treatment of cancer.展开更多
Boron neutron capture therapy(BNCT)has emerged as a promising treatment for cancers,offering a unique approach to selectively target tumor cells while sparing healthy tissues.Despite its clinical utility,the widesprea...Boron neutron capture therapy(BNCT)has emerged as a promising treatment for cancers,offering a unique approach to selectively target tumor cells while sparing healthy tissues.Despite its clinical utility,the widespread use of fructose-BPA(F-BPA)has been hampered by its limited ability to penetrate the blood-brain barrier(BBB)and potential risks for patients with certain complications such as diabetes,hyperuricemia,and gout,particularly with substantial dosages.Herein,a series of novel BPA derivatives were synthesized.After the primary screening,geniposide-BPA(G-BPA)and salidroside-BPA(S-BPA)exhibited high water solubility,low cytotoxicity and safe profiles for intravenous injection.Furthermore,both G-BPA and S-BPA had demonstrated superior efficacy in vitro against the 4T1 cell line compared with F-BPA.Notably,S-BPA displayed optimal BBB penetration capability,as evidenced by in vitro BBB models and glioblastoma models in vivo,surpassing all other BPA derivative candidates.Meanwhile,GBPA also exhibited enhanced performance relative to the clinical drug F-BPA.In brief,G-BPA and S-BPA,as novel BPA derivatives,demonstrated notable safety profiles and remarkable boron delivery capabilities,thereby offering promising therapeutic options for BNCT in the clinic.展开更多
Lapatinib ditosylate (Tyverb?) is a potent and selective oral dual receptor tyrosine kinase inhibitor (TKI), preventing autophosphorylation of epidermal growth factor receptor (EGFR/ErbB1) and human epidermal growth f...Lapatinib ditosylate (Tyverb?) is a potent and selective oral dual receptor tyrosine kinase inhibitor (TKI), preventing autophosphorylation of epidermal growth factor receptor (EGFR/ErbB1) and human epidermal growth factor receptor 2 (HER2/ErbB2) intracellular domain. This interference blocks the Ras/Raf MAPKs and PI3K/Akt pathways, that lead to uncontrolled cellular proliferation and survival. After the demonstration of its effectiveness and safety in HER2-overexpressed breast cancer, in 2007 the US Food and Drug Administration (FDA) approved this molecule in combination with capecitabine, in patients with locally advanced or metastatic disease, that progressed after previous treatment with anthracyclines, taxanes and trastuzumab. In 2010, Lapatinib received approval for the treatment of postmenopausal women with hormone receptor positive metastatic breast cancer in combination with letrozole. The most common adverse events (AE) are: anorexia, insomnia, diarrhea and skin rash and mild cardiovascular toxicity. This paper reviews the most important studies on Lapatinib in advanced breast cancer. However, promising results were recently reported on this drug, also in adjuvant setting and in combination with other target drugs, which warrant further investigation for the future.展开更多
Objective: To investigate the anticancer activity of two diterpenes [palmonine F (C1) and palmonine D (C2)] and three steroids [cholesta-5,22-dien-3β-ol (C3), stigmasterol (C4) and 5α-cholest-5-en-3β-ol (C5)], isol...Objective: To investigate the anticancer activity of two diterpenes [palmonine F (C1) and palmonine D (C2)] and three steroids [cholesta-5,22-dien-3β-ol (C3), stigmasterol (C4) and 5α-cholest-5-en-3β-ol (C5)], isolated from the Mediterranean gorgonian Eunicella singularis, against MCF-7 breast cancer cell line. Methods: This study was performed on standard monolayer two-dimensional (2D) model to evaluate apoptosis by means of AnnexinV-FITC/PI flow cytometry and on three-dimensional (3D) spheroid model using Celigo imaging cytometer for spheroids size analysis. Results: Results indicated that both diterpenes and steroids exhibited an important apoptotic activity in a concentration-dependent manner with EC50 values of 13, 49, 30, 66 and 65 μg/mL for C1, C2, C3, C4 and C5, respectively. Treatment of MCF-73D cell model with C1–C5 induced growth regression of spheroids in a concentration-dependent manner similar to the clinical anti-breast cancer drug Taxol;over ten days of incubation, growth rates were < 1.5 at Day 10 with all tested compounds at 200 μg/mL. Conclusions: The present study indicates that the two diterpenes C1 and C2 and the three steroids C3, C4 and C5, isolated from Eunicella singularis, might be used as anti-breast cancer candidate drugs for further development.展开更多
With increasingly explored ideologies and technologies for potential applications of artificial intelligence(AI)in oncology,we here describe a holistic and structured concept termed intelligent oncology.Intelligent on...With increasingly explored ideologies and technologies for potential applications of artificial intelligence(AI)in oncology,we here describe a holistic and structured concept termed intelligent oncology.Intelligent oncology is defined as a cross-disciplinary specialty which integrates oncology,radiology,pathology,molecular biology,multi-omics and computer sciences,aiming to promote cancer prevention,screening,early diagnosis and precision treatment.The development of intelligent oncology has been facilitated by fast AI technology development such as natural language processing,machine/deep learning,computer vision,and robotic process automation.While the concept and applications of intelligent oncology is still in its infancy,and there are still many hurdles and challenges,we are optimistic that it will play a pivotal role for the future of basic,translational and clinical oncology.展开更多
文摘Gastric cancer is a multifactorial neoplastic pathology numbering among its causes both environmental and genetic predisposing factors. It is mainly diffused in South America and South-East Asia, where it shows the highest morbility percentages and it is relatively scarcely diffused in Western countries and North America. Although molecular mechanisms leading to gastric cancer development are only partially known, three main causes are well characterized: Helicobacter pylori(H. pylori) infection, diet rich in salted and/or smoked food and red meat, and epithelial cadherin(E-cadherin) mutations. Unhealthy diet and H. pylori infection are able to induce in stomach cancer cells genotypic and phenotypic transformation, but their effects may be crossed by a diet rich in vegetables and fresh fruits. Various authors have recently focused their attention on the importance of a well balanced diet, suggesting a necessary dietary education starting from childhood. A constant surveillance will be necessary in people carrying E-cadherin mutations, since they are highly prone in developing gastric cancer, also within the inner stomach layers. Above all in the United States, several carriers decided to undergo a gastrectomy, preferring changing their lifestyle than living with the awareness of the development of a possible gastric cancer. This kind of choice is strictly personal, hence a decisioncannot be suggested within the clinical management. Here we summarize the key points of gastric cancer prevention analyzing possible strategies referred to the different predisposing factors. We will discuss about the effects of diet, H. pylori infection and E-cadherin mutations and how each of them can be handled.
基金Supported by The Capital Health Development Special Scientific Research Projects,No.2014-2-2154National Natural Science Foundation of China,No.81471761 and No.81501568
文摘AIM The purpose of this study was to evaluate the diagnostic value of trefoil factor family 3(TFF3) for the early detection of colorectal cancer(CC). METHODS Serum TFF3 and carcino-embryonic antigen(CEA) were detected in 527 individuals, including 115 healthy control(HC), 198 colorectal adenoma(CA), and 214 CC individuals in the training group. RESULTS Serum TFF3 showed no significant correlation with age, gender, or tumor location but showed significant correlation with the tumor stage. Serum TFF3 in the CC group was significantly higher than in the HC or CA group. The AUC values of TFF3 for discriminating between HC and CC and between CA and CC were 0.930(0.903, 0.958) and 0.834(0.796, 0.873). A multivariate model combining TFF3 and CEA was built. Compared to TFF3 or CEA alone, the multivariate model showed significant improvement(P < 0.001). For discriminating between HC and CC, HC and early stage CC, HC and advanced stage CC, CA and CC, CA and early stage CC, and CA and advanced stage CC in the training group, the sensitivities were 92.99%, 91.46%, 93.18%, 73.83%, 76.83%, and 81.82%, and the specificities were 91.30%, 91.30%, 93.91%, 88.38%, 77.27%, and 88.38%, respectively. After validation, the sensitivities were 89.39%, 85.71%, 90.79%, 72.73%, 71.43%, and 78.95%, and the specificities were 87.85%, 87.85%, 2.52%, 87.85%, 80.77%, and 87.50%, respectively. CONCLUSION The multivariate diagnostic model that included TFF3 and CEA showed significant improvement over the conventional biomarker CEA and might provide a potential method for the early detection of CC.
文摘AIM： We optimized a rapid and efficient tissue lysis method using the MagNA Lyser （Roche, Germany）. Using this novel method combined with immunoblot analysis, we investigated the correlation between abnormal Bcl-XL expression and clinicopathological characteristics in colorectal cancer. METHODS： Tissue samples from Sprague-Dawley rats were tested to determine optimal lysis conditions for use with MagNA Lyser. We next used the new method to extract tissue proteins from the tumor tissue of a colorectal cancer patient. The availability of extractable tissue proteins for proteomic study was demonstrated by two-dimensional （2D） gel electrophoresis and subsequent matrix-assisted laser desorption/ionization time-of-flight （MALDI-TOF） mass spectrometry. In addition, we prepared tissue lysates from paired tumor tissues and adjacent nontumor tissues of 50 colorectal carcinoma patients. Ensuing immunoblot analyses were performed to detect the level of Bcl-X, expression. RESULTS： The optimal sample sizes processed were found to be around 200 mg, with oscillation frequency of 6 500 r/rain for 80 s. Test of the first human tissue lysate confirmed that the MagNA Lyser method was adequate for protein extraction and subsequent identification by current proteomic protocols. The method was also applicable to immunoblot analysis. Thirty of 50 （60%） colorectal patients exhibited higher level of Bcl-XL expression in their tumor tissues. Raised level of Bcl-XL expression correlated with patients＇ gender and tumor cell proliferation index （P= 0.037 and P〈0.001, respectively）, but was independent of clinicopathological characteristics and overall survival. CONCLUSION： We report a novel tissue lysis method applicable to proteomic and immunoblot analyses, which can facilitate the discovery and detection of cancer protein alterations.
文摘Objective: Targeting mutated EGFR by EGFR-tyrosine kinase inhibitors (EGFR-TKI) is a potent approach to a subset of non-small cell lung cancer (NSCLC). However, the response to EGFR-TKI varies in individual cases even among tumors carrying the same?EGFR?mutation, suggesting the involvement of modifying factors. To characterize possible modifiers, we examined mutation state of the?EGFR?and the?KRAS?genes in Japanese NSCLC and compared them with the methylation state of lung tumor suppressors, the?CADM1 and?4.1B,?whose products have potentials to modify the functions of EGFR or KRAS. Materials and methods: A total of 103 Japanese NSCLC and 11 NSCLC cell lines were examined. Genomic DNA of exons 18–21 of the?EGFR?and exons 1 and 2 of the?KRAS?were amplified by polymerase chain reaction (PCR), followed by single-strand conformation polymorphism analysis and direct sequencing. Methylation status of gene promoters in NSCLC cells were examined by methylation-specific PCR. Results: Mutations of the?EGFR?and?KRAS?were detected mutually exclusively in 27 and 11 out of 103 NSCLC cases, respectively.?EGFR?mutations were observed exclusively in adenocarcinoma (27 of 69, 41%) and preferentially in tumors from female and non-smokers (p < 0.00001). Eight (30%) and 12 (44%) of 27 tumors carrying mutated?EGFR?and 4 (36%) and 8 (73%) of 11 tumors carrying mutated?KRAS?showed methylation of the?CADM1 and 4.1B, respectively.?EGFR-mutated tumors with methylation of either?CADM1 or 4.1B?showed more malignant features than those with unmethylated?CADM1 and 4.1B?(p < 0.05). Conclusion: Methylation state of the?CADM1 and?4.1B?are independent of the mutation status of the?EGFR?or?KRAS?but play roles in the malignant progression of NSCLC. Integration of epigenetic information would be useful for identifying possible modifiers to predict the response or recurrence of lung adenocarcinoma to the EGFR-TKI therapy.
基金Key research and development plan of Shanxi Province(No.201803D31110,201603D321068)Scientific research project of Shanxi Provincial Health and Family Planning Commission(No.2018045)。
文摘Prostate cancer is a common malignant tumor in men,which seriously endangers men's health.At present,in the treatment of prostate cancer in different stages,the survival of patients shows differences,and the survival rate of early prostate cancer is high.The prognosis is good,the survival rate of advanced prostate cancer is low,and the prognosis is poor.Digital rectal examination combined with serum PSA detection is currently recognized as the best method for early prostate cancer screening.However,the specificity of PSA is poor,and a large number of prostate cancer patients are overdiagnosed and overtreated.At the same time,the treatment of advanced prostate cancer also needs more reliable biomarkers to judge the treatment effect and assist clinical decision-making.
文摘Interleukin-11 （IL-11） is a cytokine of IL-6 family that mediates signal transduction through a common signal transduction molecule glycoprotein 130gp130. JAK/STAT, Ras/Erk and PI3K-mediated pathways are involved in the IL-11 signaling pathway. IL-11 has traditionally been thought to be an anti-inflammatory cytokine that has a complex role in the body＇s immune response. Simultaneously, the activation of STAT3 by IL-11 provides a functional link to support the survival and growth of cancer cells. There is also evidence that IL-11 may play a role in promoting liver cancer through wound healing mechanisms. In recent years, studies have found that IL-11 could stimulate the development of tumors via promoting the proliferation and inhibiting the apoptosis of cancer cells, mediating the tolerance of cancer cells to radiotherapy and chemotherapy, and mediating the growth and survival of early microtransferred colonies. Sustained activation of JAK-STAT and PI3K-AKT signaling pathway, up-regulating the expression of IL-11 receptor and hypoxia microenvironment mediated by HIF-1a and AP-1 transcription factors are involved in the progression of cancer. Therefore, targeted therapies that treat the over expression of IL-11 or IL-11 receptors and IL-11 signaling pathway such as the JAK 1/2 and STAT3 inhibitor in cancer patients has the potential to completely relieve the tumor, which may provide us a new idea for the treatment of cancer.
基金supported by Guangdong Basic and Applied Basic Research Foundation(No.2021B1515120065)National Natural Science Foundation of China(Nos.82202339,32271420,82202307)+3 种基金China Postdoctoral Science Foundation(Nos.2022M711527,2021M701640)Science Fund for Creative Research Groups of Nature Science Foundation of Hebei Province(No.B2021201038)National High-End Foreign Expert Recruitment Plan(No.G2022003007L)Natural Science Foundation of Hebei Province(No.B2023201108).
文摘Boron neutron capture therapy(BNCT)has emerged as a promising treatment for cancers,offering a unique approach to selectively target tumor cells while sparing healthy tissues.Despite its clinical utility,the widespread use of fructose-BPA(F-BPA)has been hampered by its limited ability to penetrate the blood-brain barrier(BBB)and potential risks for patients with certain complications such as diabetes,hyperuricemia,and gout,particularly with substantial dosages.Herein,a series of novel BPA derivatives were synthesized.After the primary screening,geniposide-BPA(G-BPA)and salidroside-BPA(S-BPA)exhibited high water solubility,low cytotoxicity and safe profiles for intravenous injection.Furthermore,both G-BPA and S-BPA had demonstrated superior efficacy in vitro against the 4T1 cell line compared with F-BPA.Notably,S-BPA displayed optimal BBB penetration capability,as evidenced by in vitro BBB models and glioblastoma models in vivo,surpassing all other BPA derivative candidates.Meanwhile,GBPA also exhibited enhanced performance relative to the clinical drug F-BPA.In brief,G-BPA and S-BPA,as novel BPA derivatives,demonstrated notable safety profiles and remarkable boron delivery capabilities,thereby offering promising therapeutic options for BNCT in the clinic.
文摘Lapatinib ditosylate (Tyverb?) is a potent and selective oral dual receptor tyrosine kinase inhibitor (TKI), preventing autophosphorylation of epidermal growth factor receptor (EGFR/ErbB1) and human epidermal growth factor receptor 2 (HER2/ErbB2) intracellular domain. This interference blocks the Ras/Raf MAPKs and PI3K/Akt pathways, that lead to uncontrolled cellular proliferation and survival. After the demonstration of its effectiveness and safety in HER2-overexpressed breast cancer, in 2007 the US Food and Drug Administration (FDA) approved this molecule in combination with capecitabine, in patients with locally advanced or metastatic disease, that progressed after previous treatment with anthracyclines, taxanes and trastuzumab. In 2010, Lapatinib received approval for the treatment of postmenopausal women with hormone receptor positive metastatic breast cancer in combination with letrozole. The most common adverse events (AE) are: anorexia, insomnia, diarrhea and skin rash and mild cardiovascular toxicity. This paper reviews the most important studies on Lapatinib in advanced breast cancer. However, promising results were recently reported on this drug, also in adjuvant setting and in combination with other target drugs, which warrant further investigation for the future.
基金Ministry of Higher Education,Scientific Research and Technology,Tunisia,MHSSR of Tunisia(Grant No.11/TM06).
文摘Objective: To investigate the anticancer activity of two diterpenes [palmonine F (C1) and palmonine D (C2)] and three steroids [cholesta-5,22-dien-3β-ol (C3), stigmasterol (C4) and 5α-cholest-5-en-3β-ol (C5)], isolated from the Mediterranean gorgonian Eunicella singularis, against MCF-7 breast cancer cell line. Methods: This study was performed on standard monolayer two-dimensional (2D) model to evaluate apoptosis by means of AnnexinV-FITC/PI flow cytometry and on three-dimensional (3D) spheroid model using Celigo imaging cytometer for spheroids size analysis. Results: Results indicated that both diterpenes and steroids exhibited an important apoptotic activity in a concentration-dependent manner with EC50 values of 13, 49, 30, 66 and 65 μg/mL for C1, C2, C3, C4 and C5, respectively. Treatment of MCF-73D cell model with C1–C5 induced growth regression of spheroids in a concentration-dependent manner similar to the clinical anti-breast cancer drug Taxol;over ten days of incubation, growth rates were < 1.5 at Day 10 with all tested compounds at 200 μg/mL. Conclusions: The present study indicates that the two diterpenes C1 and C2 and the three steroids C3, C4 and C5, isolated from Eunicella singularis, might be used as anti-breast cancer candidate drugs for further development.
基金supported by the National Natural Science Foundation of China(grant numbers:81974464,61906022)Chongqing Natural Science Foundation(grant number:cstc2020jcyj-msxmX0482)Chongqing University Research Fund(grant number:2021CDJXKJC004).
文摘With increasingly explored ideologies and technologies for potential applications of artificial intelligence(AI)in oncology,we here describe a holistic and structured concept termed intelligent oncology.Intelligent oncology is defined as a cross-disciplinary specialty which integrates oncology,radiology,pathology,molecular biology,multi-omics and computer sciences,aiming to promote cancer prevention,screening,early diagnosis and precision treatment.The development of intelligent oncology has been facilitated by fast AI technology development such as natural language processing,machine/deep learning,computer vision,and robotic process automation.While the concept and applications of intelligent oncology is still in its infancy,and there are still many hurdles and challenges,we are optimistic that it will play a pivotal role for the future of basic,translational and clinical oncology.
