AIM: To establish an accurate and rapid stem-loop reverse transcriptional real-time PCR (RT-PCR) method to quantify human let-7a miRNA in gastric cancer. METHODS: According to the sequence of let-7a miRNA,the stem-loo...AIM: To establish an accurate and rapid stem-loop reverse transcriptional real-time PCR (RT-PCR) method to quantify human let-7a miRNA in gastric cancer. METHODS: According to the sequence of let-7a miRNA,the stem-loop reverse transcriptional primer,the primers and quantitative MGB probes of real-time PCR were designed and synthesized. The dynamic range and the sensitivity of quantitative reverse transcriptional real-time PCR were determined. The levels of let-7a miRNA were examined in 32 gastric carcinoma samples by stem-loop RT-PCR method. RESULTS: The dynamic range and sensitivity of the let-7a miRNA quantification scheme were evaluated,the result showed the assay could precisely detect 10 copies of mature let-7a miRNA in as few as 0.05 ng of total RNA of gastric mucosa. The results of specificity analysis showed no fluorescence signal occurred even though 50 ng of human genomic DNA was added to the reverse transcription (RT) reaction. The expression level of let-7a miRNA in gastric tumor tissues was significantly lower compared to normal tissues in 14 samples from 32 patients. CONCLUSION: The stem-loop RT-PCR is a reliable method to detect let-7a miRNA which may play an important role in the development of gastric carcinoma.展开更多
Immune checkpoint inhibitors are increasingly drawing much attention in the therapeutic development for cancer treatment. However, many cancer patients do not respond to treatments with immune checkpoint inhibitors, p...Immune checkpoint inhibitors are increasingly drawing much attention in the therapeutic development for cancer treatment. However, many cancer patients do not respond to treatments with immune checkpoint inhibitors, partly because of the lack of tumor-infiltrating effector T cells. Cancer vaccines may prime patients for treatments with immune checkpoint inhibitors by inducing effector T-ceU infiltration into the tumors and immune checkpoint signals. The combination of cancer vaccine and an immune checkpoint inhibitor may function synergistically to induce more effective antitumor immune responses, and clinical trials to test the combination are currently ongoing.展开更多
The development of immunotherapies for lymphoma has undergone a revolutionary evolution over the past decades. Since the advent of rituximab as the first successful immunotherapy for B-cell non-Hodgkin lymphoma over t...The development of immunotherapies for lymphoma has undergone a revolutionary evolution over the past decades. Since the advent of rituximab as the first successful immunotherapy for B-cell non-Hodgkin lymphoma over two decades ago, a plethora of new immunotherapeutic approaches to treat lymphoma has ensued. Four of the most exciting classes of immunotherapies include:chimeric antigen receptor T-cells, bispecific antibodies, immune checkpoint inhibitors, and vaccines. However, with addition of these novel therapies the appropriate timing of treatment, optimal patient population, duration of therapy, toxicity, and cost must be considered. In this review, we describe the most-promising immunotherapeutic approaches for the treatment of lymphoma in clinical development, specifically focusing on clinical trials performed to date and strategies for improvement.展开更多
AIM：To evaluate the long-term histological outcome of patients transplanted for HBV-related liver disease and given HBIg prophylaxis indefinitely after LT. METHODS： Forty-two consecutive patients transplanted for he...AIM：To evaluate the long-term histological outcome of patients transplanted for HBV-related liver disease and given HBIg prophylaxis indefinitely after LT. METHODS： Forty-two consecutive patients transplanted for hepatitis B were prospectively studied. HBsAg, HBVDNA and liver function tests were evaluated in the serum 3, 6 and 12 mo after LT and then yearly. LB was obtained 6 and 12 mo after LT and yearly thereafter. Chronic hepatitis （CH） B after LT was classified as minimal, mild, moderate or severe. RESULTS： HBV recurred in 7/42 （16.6%） patients after 6-96 mo of follow-up. A hundred and eightyseven LB were evaluated. Four of 7 patients with graft reinfection, all with unknown HBV DNA status before LT, developed cirrhosis at 12-36 mo of follow-up. Of the 122 LB obtained from 28 HBsAg＋/HCV- recipients with no HBV recurrence after LT, all biopsies were completely normal in only 2 patients （7.1%）, minimal/non-specific changes were observed in 18 （64.2%）, and at least 1 biopsy showed CH in the remaining 8 （28.5%）. Twentynine LB obtained from 7 patients transplanted for HBVHCV cirrhosis and remaining HBsAg- after LT revealed recurrent CH-C. Actuarial survival was similar in patients with HBsAg＋ or HBsAg- liver diseases.CONCLUSION： Though protocol biopsies may enable the detection of graft dysfunction at an early stage, the risk of progression and the clinical significance of these findings remains to be determined.展开更多
Melanoma is the deadliest form of skin cancer and has an incidence that is rising faster than any other solid tumor. Metastatic melanoma treatment has considerably progressed in the past five years with the introducti...Melanoma is the deadliest form of skin cancer and has an incidence that is rising faster than any other solid tumor. Metastatic melanoma treatment has considerably progressed in the past five years with the introduction of targeted therapy(BRAF and MEK inhibitors) and immune checkpoint blockade(anti-CTLA4, anti-PD-1, and anti-PD-L1). However, each treatment modality has limitations. Treatment with targeted therapy has been associated with a high response rate, but with short-term responses. Conversely, treatment with immune checkpoint blockade has a lower response rate, but with longterm responses. Targeted therapy affects antitumor immunity, and synergy may exist when targeted therapy is combined with immunotherapy. This article presents a brief review of the rationale and evidence for the potential synergy between targeted therapy and immune checkpoint blockade. Challenges and directions for future studies are also proposed.展开更多
We report a case of a poorly differentiated epithelial tumour of the rectum with a highly pleomorphic morphology and an aberrant immunophenotype, including the expression of epithelial markers, the focal parameter of ...We report a case of a poorly differentiated epithelial tumour of the rectum with a highly pleomorphic morphology and an aberrant immunophenotype, including the expression of epithelial markers, the focal parameter of neuroendocrine differentiation, and the unexpected detection of CD-117 overexpression. A 69-year-old man was admitted to our clinic complaining of rectal bleeding and weight loss. Colonoscopy showed an ulcerative bleeding mass located about 8 cm from the anal verge. Abdominal and pelvis CT scans demonstrated a large low-density lesion with extracanalicular growth from the middle rectum, with local lymph-node spread, and without tumour infiltration of other pelvic organs, or evidence of distant intra-abdominal spread. The patient underwent a low anterior resection for rectal cancer together with wide resection of lymph nodes. In immunohistochemical analysis, pankeratin and Epithelial Membrane Antigen (EMA) immunolabeling proved the epithelial nature of the tumor cells. Chromogranin A and Leukocyte Common Antigen (LCA) were negative, whereas CD-56 expression was scanty and Neuron Specific Enolase (NSA) was heavily and diffusely expressed. Ki67 immunoexpression was particularly increased. Interestingly, the intense c-kit immunoreactivity (100%) was a common feature. The above phenotypic and immunohistochemical profile was consistent with an anaplastic carcinoma of the large intestine, with focal neuroendocrine differentiation and diffuse immunoreactivity to c-kit protein. Given the resistance of this tumor to conventional chemotherapy and radiation, the incidence of the c-kit alteration may represent a novel approach to a gene-directed treatment using a c-kit inhibitor (STI571) similar to that which has been proposed in GISTs.展开更多
Pancreatic cancer is among the most lethal malignancies resistant to conventional therapies. The urgent need fornew therapies has turned the spotlights on immunotherapy. In recent years, a growing body of evidence has...Pancreatic cancer is among the most lethal malignancies resistant to conventional therapies. The urgent need fornew therapies has turned the spotlights on immunotherapy. In recent years, a growing body of evidence has alreadybeen gathered regarding the efficacy of genetic engineering modified T-cells, checkpoint inhibitors of T-cells, killercells induced by dendritic cells and cytokine in patients with pancreatic cancer. Cryoimmunotherapy in situ andextra-tumor and immunotherapy combined with chemotherapy could also increase the effectiveness. Research ofpancreatic cancer vaccine has made some progress. The immunity enhancing function of some traditional herbshave been reported, such as Ginsenoside Rg3, which could enhance T-cell subsets and NK cell activity inpancreatic cancer patients with chemotherapy.展开更多
Objective： To observe the expression and distribution of adult rat axon guidance cues Netrin- 1 and Slit2 at different time points after spinal cord injury and to investigate the guidance mechanism of regenerated axo...Objective： To observe the expression and distribution of adult rat axon guidance cues Netrin- 1 and Slit2 at different time points after spinal cord injury and to investigate the guidance mechanism of regenerated axons. Methods： Twenty adult Sprague Dawley （SD） rats were divided randomly into five groups with 4 in each. Four groups of them were used to make Allen＇s spinal cord punch models and we took materials randomly from one of them on the 2nd, 4th, 7th and 14th day respectively after operation. The left one group was taken as the control group. Immun- ofluorescence laser confocal scan was used to examine the co-expression and localization of Netrin- 1 and Slit2 proteinsin the injured site of the spinal cord. Results： Within two weeks after SCI, the expression of Netrin- 1 and Slit2 proteins increased temporarily and there was co-expression of them on the neuron plasma membrane. Conclusions： Synchronous high expression and co-expression of axon attractant Netrin-1 and repellent Slit2 are found in the adult rat injured spinal cord in the damaged local and vicinity parts, and probably, they act as the key regulators of axon guidance regeneration.展开更多
We develop an influenza pandemic model with quarantine and treatment, and analyze the dynamics of the model. Analytical results of the model show that, if basic repro- duction number R0 〈 1, the disease-free equilibr...We develop an influenza pandemic model with quarantine and treatment, and analyze the dynamics of the model. Analytical results of the model show that, if basic repro- duction number R0 〈 1, the disease-free equilibrium （DFE） is globally asymptotically stable, if R0〉 1, the disease is uniformly persistent. The model is then extended to assess the impact of three anti-influenza control measures, precaution, quarantine and treat- ment, by re-formulating the model as an optimal control problem. We focus primarily on controlling disease with a possible minimal the systemic cost. Pontryagin＇s maximum principle is used to characterize the optimal levels of the three controls. Numerical sim- ulations of the optimality system, using a set of reasonable parameter values, indicate that the precaution measure is more effective in reducing disease transmission than the other two control measures. The precaution measure should be emphasized.展开更多
文摘AIM: To establish an accurate and rapid stem-loop reverse transcriptional real-time PCR (RT-PCR) method to quantify human let-7a miRNA in gastric cancer. METHODS: According to the sequence of let-7a miRNA,the stem-loop reverse transcriptional primer,the primers and quantitative MGB probes of real-time PCR were designed and synthesized. The dynamic range and the sensitivity of quantitative reverse transcriptional real-time PCR were determined. The levels of let-7a miRNA were examined in 32 gastric carcinoma samples by stem-loop RT-PCR method. RESULTS: The dynamic range and sensitivity of the let-7a miRNA quantification scheme were evaluated,the result showed the assay could precisely detect 10 copies of mature let-7a miRNA in as few as 0.05 ng of total RNA of gastric mucosa. The results of specificity analysis showed no fluorescence signal occurred even though 50 ng of human genomic DNA was added to the reverse transcription (RT) reaction. The expression level of let-7a miRNA in gastric tumor tissues was significantly lower compared to normal tissues in 14 samples from 32 patients. CONCLUSION: The stem-loop RT-PCR is a reliable method to detect let-7a miRNA which may play an important role in the development of gastric carcinoma.
基金supported by the Viragh Foundation(L.Z.)National Institutes of Health(NIH)(Grant No.K23 CA148964,L.Z.)the NCI SPORE in Gastrointestinal Cancers(Grant No.P50 CA062924,L.Z.)
文摘Immune checkpoint inhibitors are increasingly drawing much attention in the therapeutic development for cancer treatment. However, many cancer patients do not respond to treatments with immune checkpoint inhibitors, partly because of the lack of tumor-infiltrating effector T cells. Cancer vaccines may prime patients for treatments with immune checkpoint inhibitors by inducing effector T-ceU infiltration into the tumors and immune checkpoint signals. The combination of cancer vaccine and an immune checkpoint inhibitor may function synergistically to induce more effective antitumor immune responses, and clinical trials to test the combination are currently ongoing.
基金supported by NIH grants(Grant No.R01CA136934,and R01 CA193167)
文摘The development of immunotherapies for lymphoma has undergone a revolutionary evolution over the past decades. Since the advent of rituximab as the first successful immunotherapy for B-cell non-Hodgkin lymphoma over two decades ago, a plethora of new immunotherapeutic approaches to treat lymphoma has ensued. Four of the most exciting classes of immunotherapies include:chimeric antigen receptor T-cells, bispecific antibodies, immune checkpoint inhibitors, and vaccines. However, with addition of these novel therapies the appropriate timing of treatment, optimal patient population, duration of therapy, toxicity, and cost must be considered. In this review, we describe the most-promising immunotherapeutic approaches for the treatment of lymphoma in clinical development, specifically focusing on clinical trials performed to date and strategies for improvement.
文摘AIM：To evaluate the long-term histological outcome of patients transplanted for HBV-related liver disease and given HBIg prophylaxis indefinitely after LT. METHODS： Forty-two consecutive patients transplanted for hepatitis B were prospectively studied. HBsAg, HBVDNA and liver function tests were evaluated in the serum 3, 6 and 12 mo after LT and then yearly. LB was obtained 6 and 12 mo after LT and yearly thereafter. Chronic hepatitis （CH） B after LT was classified as minimal, mild, moderate or severe. RESULTS： HBV recurred in 7/42 （16.6%） patients after 6-96 mo of follow-up. A hundred and eightyseven LB were evaluated. Four of 7 patients with graft reinfection, all with unknown HBV DNA status before LT, developed cirrhosis at 12-36 mo of follow-up. Of the 122 LB obtained from 28 HBsAg＋/HCV- recipients with no HBV recurrence after LT, all biopsies were completely normal in only 2 patients （7.1%）, minimal/non-specific changes were observed in 18 （64.2%）, and at least 1 biopsy showed CH in the remaining 8 （28.5%）. Twentynine LB obtained from 7 patients transplanted for HBVHCV cirrhosis and remaining HBsAg- after LT revealed recurrent CH-C. Actuarial survival was similar in patients with HBsAg＋ or HBsAg- liver diseases.CONCLUSION： Though protocol biopsies may enable the detection of graft dysfunction at an early stage, the risk of progression and the clinical significance of these findings remains to be determined.
基金NIH grants 1K08CA160692-01A1,U54CA163125-01 and the generous philanthropic support of several families whose lives have been affected by melanoma
文摘Melanoma is the deadliest form of skin cancer and has an incidence that is rising faster than any other solid tumor. Metastatic melanoma treatment has considerably progressed in the past five years with the introduction of targeted therapy(BRAF and MEK inhibitors) and immune checkpoint blockade(anti-CTLA4, anti-PD-1, and anti-PD-L1). However, each treatment modality has limitations. Treatment with targeted therapy has been associated with a high response rate, but with short-term responses. Conversely, treatment with immune checkpoint blockade has a lower response rate, but with longterm responses. Targeted therapy affects antitumor immunity, and synergy may exist when targeted therapy is combined with immunotherapy. This article presents a brief review of the rationale and evidence for the potential synergy between targeted therapy and immune checkpoint blockade. Challenges and directions for future studies are also proposed.
文摘We report a case of a poorly differentiated epithelial tumour of the rectum with a highly pleomorphic morphology and an aberrant immunophenotype, including the expression of epithelial markers, the focal parameter of neuroendocrine differentiation, and the unexpected detection of CD-117 overexpression. A 69-year-old man was admitted to our clinic complaining of rectal bleeding and weight loss. Colonoscopy showed an ulcerative bleeding mass located about 8 cm from the anal verge. Abdominal and pelvis CT scans demonstrated a large low-density lesion with extracanalicular growth from the middle rectum, with local lymph-node spread, and without tumour infiltration of other pelvic organs, or evidence of distant intra-abdominal spread. The patient underwent a low anterior resection for rectal cancer together with wide resection of lymph nodes. In immunohistochemical analysis, pankeratin and Epithelial Membrane Antigen (EMA) immunolabeling proved the epithelial nature of the tumor cells. Chromogranin A and Leukocyte Common Antigen (LCA) were negative, whereas CD-56 expression was scanty and Neuron Specific Enolase (NSA) was heavily and diffusely expressed. Ki67 immunoexpression was particularly increased. Interestingly, the intense c-kit immunoreactivity (100%) was a common feature. The above phenotypic and immunohistochemical profile was consistent with an anaplastic carcinoma of the large intestine, with focal neuroendocrine differentiation and diffuse immunoreactivity to c-kit protein. Given the resistance of this tumor to conventional chemotherapy and radiation, the incidence of the c-kit alteration may represent a novel approach to a gene-directed treatment using a c-kit inhibitor (STI571) similar to that which has been proposed in GISTs.
基金This study was supported by National Natural Science Foundation of China （81341068）.
文摘Pancreatic cancer is among the most lethal malignancies resistant to conventional therapies. The urgent need fornew therapies has turned the spotlights on immunotherapy. In recent years, a growing body of evidence has alreadybeen gathered regarding the efficacy of genetic engineering modified T-cells, checkpoint inhibitors of T-cells, killercells induced by dendritic cells and cytokine in patients with pancreatic cancer. Cryoimmunotherapy in situ andextra-tumor and immunotherapy combined with chemotherapy could also increase the effectiveness. Research ofpancreatic cancer vaccine has made some progress. The immunity enhancing function of some traditional herbshave been reported, such as Ginsenoside Rg3, which could enhance T-cell subsets and NK cell activity inpancreatic cancer patients with chemotherapy.
文摘Objective： To observe the expression and distribution of adult rat axon guidance cues Netrin- 1 and Slit2 at different time points after spinal cord injury and to investigate the guidance mechanism of regenerated axons. Methods： Twenty adult Sprague Dawley （SD） rats were divided randomly into five groups with 4 in each. Four groups of them were used to make Allen＇s spinal cord punch models and we took materials randomly from one of them on the 2nd, 4th, 7th and 14th day respectively after operation. The left one group was taken as the control group. Immun- ofluorescence laser confocal scan was used to examine the co-expression and localization of Netrin- 1 and Slit2 proteinsin the injured site of the spinal cord. Results： Within two weeks after SCI, the expression of Netrin- 1 and Slit2 proteins increased temporarily and there was co-expression of them on the neuron plasma membrane. Conclusions： Synchronous high expression and co-expression of axon attractant Netrin-1 and repellent Slit2 are found in the adult rat injured spinal cord in the damaged local and vicinity parts, and probably, they act as the key regulators of axon guidance regeneration.
文摘We develop an influenza pandemic model with quarantine and treatment, and analyze the dynamics of the model. Analytical results of the model show that, if basic repro- duction number R0 〈 1, the disease-free equilibrium （DFE） is globally asymptotically stable, if R0〉 1, the disease is uniformly persistent. The model is then extended to assess the impact of three anti-influenza control measures, precaution, quarantine and treat- ment, by re-formulating the model as an optimal control problem. We focus primarily on controlling disease with a possible minimal the systemic cost. Pontryagin＇s maximum principle is used to characterize the optimal levels of the three controls. Numerical sim- ulations of the optimality system, using a set of reasonable parameter values, indicate that the precaution measure is more effective in reducing disease transmission than the other two control measures. The precaution measure should be emphasized.
