Supplement of Experimental Study on the properties of the blood remained in the heart of the dead body due to internal bleeding

On the study of the physical and chemical properties of the blood remained in the heart of the rabbit which died of the internal bleeding by cutting off the mesentery artery, comparing with Irie's reports in which he examined the properties of the blood remained in the heart of the dead body due to external bleeding by cutting off the carotid artery and internal bleeding by liver injury, the following results were obtained: 1) In this experiment: a) the quantity of bleeding was larger relatively, and the time of death was longer than in Irie's experiments; b) the blood sedimentation rate and the blood coagulation time prolonged like the case of liver injury; c) the blood sugar increased like the case of liver injury; d) the quantity of serum calcium and phosphor increased like the case of liver injury. 2) There were no obvious differences between this experiment cud the experiment of liver injury

Experimental Studies on the Postmortem Changes of Enzymic Activities in the Organs and Tissues

The studies on the changes of the activities of cathepsin, amylase and phosphatase in the enzyme solution extracted from the organs and tissues led to the following results. Report I. As the fundamental experiment, the activities of Papayotin and Taka-diastase which hydrolysed the substrates (gelatine and starch) was kept still after 144 hours in an incubator, but the activities of them in their mixed solution was lost more rapidly. Report 2. The activities of cathepsin and phosphatase in the enzyme-solution extracted from the liver and the activity of phosphatase from the femur of the dog was kept still in an incubator after 20 days, but the activity of amylase from the liver was already lost after 3 or 4 days. Report 3. The activities of amylase in the brain, lung, liver, kidney and the thighmuscle of the rabbit was lost 24 to 36 hours after death in summer, 60 to 72 hours in spring and autumn, but was kept still 72 hours in winter

Enzymochemical Studies on the Parenchymatous Poisoning

In order to investigate the cause of the toxic action of the parenchymatous poisoning which are represented by arsenic and phosphor poisoning, enzymochemical studies on the influences of the parenchymatous poisoning to the activities of cathepsin, phcsphatase and amylase in the organs and serum have been attempad, and the following results were obtained by the experiments of Rep. I, 2 and 3. Rep. I: Uuder the arsenic poisoning, the serum albumin decreased and the activity of cathepsin in the liver was inhibited, but the serum γ-globulin increased and the activity of cathepsin in the serum was strengthened. Rep. 2: The activity of phosphatase in the brain, heart, lung, liver, kidney and serum was inhibited under the acute arsenic poisoning, but the activity of phosphatase in the serum and the organs except the heart were slightly strengthened under the chronic poisoning. Rep. 3: The activity of amylase in the brain, heart, lung, liver, kindey and serum were inhibited slightly under the acute arsenic poisoning, but under the suba_ute and chronic poisoning, the activity of amylase were strengthened obviously, especially in the lung, kidney and heart

Table_1_Circulating tumor-associated antigen-specific IFNγ+4-1BB+ CD8+ T cells as peripheral biomarkers of treatment outcomes in patients with pancreatic cancer.pdf

CD8+ T cells affect the outcomes of pancreatic ductal adenocarcinoma (PDAC). Using tissue samples at pre-treatment to monitor the immune response is challenging, while blood samples are beneficial in overcoming this limitation. In this study, we measured peripheral antigen-specific CD8+ T cell responses against four different tumor-associated antigens (TAAs) in PDAC using flow cytometry and investigated their relationships with clinical features. We analyzed the optimal timing within the treatment course for effective immune checkpoint inhibition in vitro. We demonstrated that the frequency of TAA-specific IFNγ+4-1BB+ CD8+ T cells was correlated with a fold reduction in CA19-9 before and after neoadjuvant therapy. Moreover, patients with TAA-specific IFNγ+4-1BB+ CD8+ T cells after surgery exhibited a significantly improved disease-free survival. Anti-PD-1 treatment in vitro increased the frequency of TAA-specific IFNγ+4-1BB+ CD8+ T cells before neoadjuvant therapy in patients, suggesting the importance of the timing of anti-PD-1 inhibition during the treatment regimen. Our results indicate that peripheral immunophenotyping, combined with highly sensitive identification of TAA-specific responses in vitro as well as detailed CD8+ T cell subset profiling via ex vivo analysis, may serve as peripheral biomarkers to predict treatment outcomes and therapeutic efficacy of immunotherapy plus neoadjuvant chemotherapy.</p

DataSheet_1_Circulating tumor-associated antigen-specific IFNγ+4-1BB+ CD8+ T cells as peripheral biomarkers of treatment outcomes in patients with pancreatic cancer.pdf

CD8+ T cells affect the outcomes of pancreatic ductal adenocarcinoma (PDAC). Using tissue samples at pre-treatment to monitor the immune response is challenging, while blood samples are beneficial in overcoming this limitation. In this study, we measured peripheral antigen-specific CD8+ T cell responses against four different tumor-associated antigens (TAAs) in PDAC using flow cytometry and investigated their relationships with clinical features. We analyzed the optimal timing within the treatment course for effective immune checkpoint inhibition in vitro. We demonstrated that the frequency of TAA-specific IFNγ+4-1BB+ CD8+ T cells was correlated with a fold reduction in CA19-9 before and after neoadjuvant therapy. Moreover, patients with TAA-specific IFNγ+4-1BB+ CD8+ T cells after surgery exhibited a significantly improved disease-free survival. Anti-PD-1 treatment in vitro increased the frequency of TAA-specific IFNγ+4-1BB+ CD8+ T cells before neoadjuvant therapy in patients, suggesting the importance of the timing of anti-PD-1 inhibition during the treatment regimen. Our results indicate that peripheral immunophenotyping, combined with highly sensitive identification of TAA-specific responses in vitro as well as detailed CD8+ T cell subset profiling via ex vivo analysis, may serve as peripheral biomarkers to predict treatment outcomes and therapeutic efficacy of immunotherapy plus neoadjuvant chemotherapy.</p

Circulating tumor-associated antigen-specific IFNγ+4-1BB+ CD8+ T cells as peripheral biomarkers of treatment outcomes in patients with pancreatic cancer

CD8+ T cells affect the outcomes of pancreatic ductal adenocarcinoma (PDAC). Using tissue samples at pre-treatment to monitor the immune response is challenging, while blood samples are beneficial in overcoming this limitation. In this study, we measured peripheral antigen-specific CD8+ T cell responses against four different tumor-associated antigens (TAAs) in PDAC using flow cytometry and investigated their relationships with clinical features. We analyzed the optimal timing within the treatment course for effective immune checkpoint inhibition in vitro. We demonstrated that the frequency of TAA-specific IFNγ+4-1BB+ CD8+ T cells was correlated with a fold reduction in CA19-9 before and after neoadjuvant therapy. Moreover, patients with TAA-specific IFNγ+4-1BB+ CD8+ T cells after surgery exhibited a significantly improved disease-free survival. Anti-PD-1 treatment in vitro increased the frequency of TAA-specific IFNγ+4-1BB+ CD8+ T cells before neoadjuvant therapy in patients, suggesting the importance of the timing of anti-PD-1 inhibition during the treatment regimen. Our results indicate that peripheral immunophenotyping, combined with highly sensitive identification of TAA-specific responses in vitro as well as detailed CD8+ T cell subset profiling via ex vivo analysis, may serve as peripheral biomarkers to predict treatment outcomes and therapeutic efficacy of immunotherapy plus neoadjuvant chemotherapy