Three genetic mechanisms activate oncogenes in human neoplasms: 1) mutations, 2) gene amplification, and 3) chromosome rearrangements. These mechanisms result in either an alteration of protooncogene structure or an i...Three genetic mechanisms activate oncogenes in human neoplasms: 1) mutations, 2) gene amplification, and 3) chromosome rearrangements. These mechanisms result in either an alteration of protooncogene structure or an increase in protooncogene expression. The role of epigenetic aberrancies in carcinogenesis has been described earlier however to clinicians, the biological implications of epigenetic therapies to prevent cancer and the mechanisms involved have been a mystery. Furthermore, there is no biomarker suggested to track the carcinogenesis steps long before cancer develops, and this has caused a significant lack of proactive and preventive measures to be taken as all recommendations in preventive oncology are either deficiently and blindly made or through screening methods which are too late in the game. Here we explored a very different approach by applying our deepest understanding of epigenetics and carcinogenesis and even further we developed a framework where our clinical findings could translate to the research and vice versa by generating advanced and novel hypotheses on “how we get cancer”, by exploring the relation between the host and the tumor cells in a way no one had perceived before. The role of specific cancer stem cell pathways is dissected and how to inhibit each of these initiators using multitargeted epigenetic therapies and off-label medications are explained. We should admit that without considering this sophisticated amazing biological network, cancer will remain an unsolved challenge. Further, we were able to solve this unsolved puzzle by bridging the gap from a hypothetical point of view/hypothesis to possibilities that explain the clinical findings we had observed, and conclude that such an approach can completely change the way practitioners are treating cancer.展开更多
Fever is prevalent in hospitalized patients. In hematology-oncology patients, it is related with infection, a disease manifestation or a consequence of immunological dysfunction. This single-center retrospective study...Fever is prevalent in hospitalized patients. In hematology-oncology patients, it is related with infection, a disease manifestation or a consequence of immunological dysfunction. This single-center retrospective study aims to determine fever prevalence, describe its causes and evaluate the impact of infection on mortality. We reviewed clinical records of 222 patients admitted to the hospital in three random months of 2015. Around 35% of all hospitalizations were complicated by fever, 42.5% of unknown origin. 90.4% were under treatment. Around 81% did antibiotics, most commonly piperacillin/tazobactam, for around 11 days. 41% changed antibiotics due to fever persistence or microbiological results. The diagnostic yield of microbiological tests was 25%;in 66.7%, a Gram-negative microorganism was isolated. We didn’t find an association between infection and mortality. We conclude that fever is common in our hematology-oncology clinic and that the team is trained to assume infection;empirical treatment is in accordance with international recommendations.展开更多
AIM To identify chromosomal copy number aberrations(CNAs) in early-stage hepatocellular carcinoma(HCC) and analyze whether they are correlated with patient prognosis.METHODS One hundred and twenty patients with early-...AIM To identify chromosomal copy number aberrations(CNAs) in early-stage hepatocellular carcinoma(HCC) and analyze whether they are correlated with patient prognosis.METHODS One hundred and twenty patients with early-stage HCC were enrolled in our study, with the collection of formalin fixed, paraffin-embedded(FFPE) specimens and clinicopathological data. Tumor areas were marked by certified pathologists on a hematoxylin and eosinstained slide, and cancer and adjacent non-cancerous tissues underwent extraction of DNA, which was analyzed with the Affymetrix Onco Scan platform to assess CNAs and loss of heterozygosity(LOH). Ten individuals with nonmalignant disease were used as the control group. Another cohort consisting of 40 patients with stage Ⅰ/Ⅱ HCC were enrolled to analyze gene expression and to correlate findings with the Onco Scan data.RESULTS Copy number amplifications occurred at chromosomes 1 q21.1-q44 and 8 q12.3-24.3 and deletions were found at 4 q13.1-q35.2, 8 p 23.2-21.1, 16 q23.3-24.3, and 17 p13.3-12, while LOH commonly occurred at 1 p32.3, 3 p21.31, 8 p23.2-21.1, 16 q22.1-24.3, and 17 p 13.3-11 in early-stage HCC. Using Cox regression analysis, we also found that a higher percentage of genome change(≥ 60%) was an independent factor for worse prognosis in early-stage HCC(P = 0.031). Among the 875 genes in the Onco Scan Gene Chip, six were independent predictors of worse disease-free survival, of which three were amplified(MYC, ELAC2, and SYK) and three were deleted(GAK, MECOM, and WRN). Further, patients with HCC who exhibited ≥ 3 CNAs involving these six genes have worse outcomes compared to those who had < 3 CNAs(P < 0.001). Similarly, Asian patients with stage I HCC from The Cancer Genome Atlas harboring CNAs with these genes were also predicted to have poorer outcomes.CONCLUSION Patients with early-stage HCC and increased genome change or CNAs involving MYC, ELAC2, SYK, GAK, MECOM, or WRN are at risk for poorer outcome after resection.展开更多
Diffusion weighted imaging(DWI) is a method of signal contrast generation based on the differences in Brownian motion. DWI is a method to evaluate the molecular function and micro-architecture of the human body. DWI s...Diffusion weighted imaging(DWI) is a method of signal contrast generation based on the differences in Brownian motion. DWI is a method to evaluate the molecular function and micro-architecture of the human body. DWI signal contrast can be quantified by apparent diffusion coefficient maps and it acts as a tool for treatment respon-se evaluation and assessment of disease progression. Ability to detect and quantify the anisotropy of diffusion leads to a new paradigm called diffusion tensor imaging(DTI). DTI is a tool for assessment of the organs with highly organised fibre structure. DWI forms an integral part of modern state-of-art magnetic resonance imaging and is indispensable in neuroimaging and oncology. DWI is a field that has been undergoing rapid technical evolution and its applications are increasing every day. This review article provides insights in to the evolution of DWI as a new imaging paradigm and provides a summary of current role of DWI in various disease processes.展开更多
AIM: To investigate the correlation between Kirsten rat sarcoma viral oncogene homolog(KRAS) status and the therapeutic effects of anti-epidermal growth factor receptor(EGFR) monoclonal antibodies(Mo Abs) in metastati...AIM: To investigate the correlation between Kirsten rat sarcoma viral oncogene homolog(KRAS) status and the therapeutic effects of anti-epidermal growth factor receptor(EGFR) monoclonal antibodies(Mo Abs) in metastatic colorectal cancer(m CRC).METHODS: Randomized controlled trials(RCTs) were identified and the association between KRAS mutation and clinical outcome in m CRC patients treated with anti-EGFR Mo Abs was investigated.Ten RCTs wereincluded in this meta-analysis.Progression-free survival and overall survival were used to assess the strength of the relationship between KRAS mutation and clinical outcome.RESULTS: In first-line treatment, survival benefit was confined to patients with wild-type KRAS.Chemotherapy regimens and angiogenesis inhibitor treatment influenced the results of the analysis.Wildtype KRAS m CRC patients did not seem to benefit from oxaliplatin-based chemotherapy(PFS: HR = 0.88, 95%CI: 0.70-1.10; OS: HR = 0.93, 95%CI: 0.82-1.04).Clinical benefit in m CRC patients was limited to therapeutic regimens which included anti-EGFR Mo Abs and fluorouracil-based therapy(PFS: HR = 0.77, 95%CI: 0.69-0.86; OS: HR = 0.85, 95%CI: 0.75-0.95).When anti-EGFR Mo Abs were used as second- or further-line treatment, clinical benefit was still confined to patients with wild-type KRAS.CONCLUSION: KRAS status is a potential predictive marker of clinical benefit due to anti-EGFR Mo Ab therapy in m CRC patients.展开更多
文摘Three genetic mechanisms activate oncogenes in human neoplasms: 1) mutations, 2) gene amplification, and 3) chromosome rearrangements. These mechanisms result in either an alteration of protooncogene structure or an increase in protooncogene expression. The role of epigenetic aberrancies in carcinogenesis has been described earlier however to clinicians, the biological implications of epigenetic therapies to prevent cancer and the mechanisms involved have been a mystery. Furthermore, there is no biomarker suggested to track the carcinogenesis steps long before cancer develops, and this has caused a significant lack of proactive and preventive measures to be taken as all recommendations in preventive oncology are either deficiently and blindly made or through screening methods which are too late in the game. Here we explored a very different approach by applying our deepest understanding of epigenetics and carcinogenesis and even further we developed a framework where our clinical findings could translate to the research and vice versa by generating advanced and novel hypotheses on “how we get cancer”, by exploring the relation between the host and the tumor cells in a way no one had perceived before. The role of specific cancer stem cell pathways is dissected and how to inhibit each of these initiators using multitargeted epigenetic therapies and off-label medications are explained. We should admit that without considering this sophisticated amazing biological network, cancer will remain an unsolved challenge. Further, we were able to solve this unsolved puzzle by bridging the gap from a hypothetical point of view/hypothesis to possibilities that explain the clinical findings we had observed, and conclude that such an approach can completely change the way practitioners are treating cancer.
文摘Fever is prevalent in hospitalized patients. In hematology-oncology patients, it is related with infection, a disease manifestation or a consequence of immunological dysfunction. This single-center retrospective study aims to determine fever prevalence, describe its causes and evaluate the impact of infection on mortality. We reviewed clinical records of 222 patients admitted to the hospital in three random months of 2015. Around 35% of all hospitalizations were complicated by fever, 42.5% of unknown origin. 90.4% were under treatment. Around 81% did antibiotics, most commonly piperacillin/tazobactam, for around 11 days. 41% changed antibiotics due to fever persistence or microbiological results. The diagnostic yield of microbiological tests was 25%;in 66.7%, a Gram-negative microorganism was isolated. We didn’t find an association between infection and mortality. We conclude that fever is common in our hematology-oncology clinic and that the team is trained to assume infection;empirical treatment is in accordance with international recommendations.
基金Supported by the Chang Gung Memorial Hospital in Taiwan,No.CMRPG 3C0951-3 and No.CMRPG 3A0671 to Yu MC,and No.CMRPD3F0011 to Tsai CN
文摘AIM To identify chromosomal copy number aberrations(CNAs) in early-stage hepatocellular carcinoma(HCC) and analyze whether they are correlated with patient prognosis.METHODS One hundred and twenty patients with early-stage HCC were enrolled in our study, with the collection of formalin fixed, paraffin-embedded(FFPE) specimens and clinicopathological data. Tumor areas were marked by certified pathologists on a hematoxylin and eosinstained slide, and cancer and adjacent non-cancerous tissues underwent extraction of DNA, which was analyzed with the Affymetrix Onco Scan platform to assess CNAs and loss of heterozygosity(LOH). Ten individuals with nonmalignant disease were used as the control group. Another cohort consisting of 40 patients with stage Ⅰ/Ⅱ HCC were enrolled to analyze gene expression and to correlate findings with the Onco Scan data.RESULTS Copy number amplifications occurred at chromosomes 1 q21.1-q44 and 8 q12.3-24.3 and deletions were found at 4 q13.1-q35.2, 8 p 23.2-21.1, 16 q23.3-24.3, and 17 p13.3-12, while LOH commonly occurred at 1 p32.3, 3 p21.31, 8 p23.2-21.1, 16 q22.1-24.3, and 17 p 13.3-11 in early-stage HCC. Using Cox regression analysis, we also found that a higher percentage of genome change(≥ 60%) was an independent factor for worse prognosis in early-stage HCC(P = 0.031). Among the 875 genes in the Onco Scan Gene Chip, six were independent predictors of worse disease-free survival, of which three were amplified(MYC, ELAC2, and SYK) and three were deleted(GAK, MECOM, and WRN). Further, patients with HCC who exhibited ≥ 3 CNAs involving these six genes have worse outcomes compared to those who had < 3 CNAs(P < 0.001). Similarly, Asian patients with stage I HCC from The Cancer Genome Atlas harboring CNAs with these genes were also predicted to have poorer outcomes.CONCLUSION Patients with early-stage HCC and increased genome change or CNAs involving MYC, ELAC2, SYK, GAK, MECOM, or WRN are at risk for poorer outcome after resection.
文摘Diffusion weighted imaging(DWI) is a method of signal contrast generation based on the differences in Brownian motion. DWI is a method to evaluate the molecular function and micro-architecture of the human body. DWI signal contrast can be quantified by apparent diffusion coefficient maps and it acts as a tool for treatment respon-se evaluation and assessment of disease progression. Ability to detect and quantify the anisotropy of diffusion leads to a new paradigm called diffusion tensor imaging(DTI). DTI is a tool for assessment of the organs with highly organised fibre structure. DWI forms an integral part of modern state-of-art magnetic resonance imaging and is indispensable in neuroimaging and oncology. DWI is a field that has been undergoing rapid technical evolution and its applications are increasing every day. This review article provides insights in to the evolution of DWI as a new imaging paradigm and provides a summary of current role of DWI in various disease processes.
文摘AIM: To investigate the correlation between Kirsten rat sarcoma viral oncogene homolog(KRAS) status and the therapeutic effects of anti-epidermal growth factor receptor(EGFR) monoclonal antibodies(Mo Abs) in metastatic colorectal cancer(m CRC).METHODS: Randomized controlled trials(RCTs) were identified and the association between KRAS mutation and clinical outcome in m CRC patients treated with anti-EGFR Mo Abs was investigated.Ten RCTs wereincluded in this meta-analysis.Progression-free survival and overall survival were used to assess the strength of the relationship between KRAS mutation and clinical outcome.RESULTS: In first-line treatment, survival benefit was confined to patients with wild-type KRAS.Chemotherapy regimens and angiogenesis inhibitor treatment influenced the results of the analysis.Wildtype KRAS m CRC patients did not seem to benefit from oxaliplatin-based chemotherapy(PFS: HR = 0.88, 95%CI: 0.70-1.10; OS: HR = 0.93, 95%CI: 0.82-1.04).Clinical benefit in m CRC patients was limited to therapeutic regimens which included anti-EGFR Mo Abs and fluorouracil-based therapy(PFS: HR = 0.77, 95%CI: 0.69-0.86; OS: HR = 0.85, 95%CI: 0.75-0.95).When anti-EGFR Mo Abs were used as second- or further-line treatment, clinical benefit was still confined to patients with wild-type KRAS.CONCLUSION: KRAS status is a potential predictive marker of clinical benefit due to anti-EGFR Mo Ab therapy in m CRC patients.
