Immune checkpoint inhibition has been established as a new treatment option for various types of carcinoma, and many clinical trials are being actively conducted as a treatment for advanced or metastatic gastric cancer, either as a monotherapy with an immune checkpoint inhibitor or as a combination therapy with standard chemotherapy. In the CheckMate-649 clinical trial to confirm the efficacy of the combination of nivolumab and chemotherapy (FP) in advanced gastric cancer and gastroesophageal junction cancer, nivolumab group showed improvement in overall survival in programmed death ligand 1-positive cancer patients compared with placebo group. Also, the combination therapy of pembrolizumab, trastuzumab and chemotherapy (FP) in first-line treatment was tested through the KEYNOTE-811 trial. The pembrolizumab group showed 22.7% of improvement in objective response rate compared with placebo group. Accordingly, the combination of nivolumab/pembrolizumab with standard chemotherapy was approved for the first-line treatment. In KEYNOTE-059 trials for patients with progressive disease after at least two lines of chemotherapy, pembrolizumab monotherapy showed improvement in objective response rate and overall survival, and the use of pembrolizumab was approved for the third-line or more treatment. In this article, we review the result of clinical trials related to immune checkpoint inhibitors that have been recently introduced in the treatment of gastric cancer.
Myeloid-derived suppressor cells (MDSCs) have strong immunosuppressive activity and are morphologically similar to conventional monocytes and granulocytes. The development and classification of these cells have, however, been controversial. The activation network of MDSCs is relatively complex, and their mechanism of action is poorly understood, creating an avenue for further research. In recent years, MDSCs have been found to play an important role in immune regulation and in effectively inhibiting the activity of effector lymphocytes. Under certain conditions, particularly in the case of tissue damage or inflammation, MDSCs play a leading role in the immune response of the central nervous system. In cancer, however, this can lead to tumor immune evasion and the development of related diseases. Under cancerous conditions, tumors often alter bone marrow formation, thus affecting progenitor cell differentiation, and ultimately, MDSC accumulation. MDSCs are important contributors to tumor progression and play a key role in promoting tumor growth and metastasis, and even reduce the efficacy of immunotherapy. Currently, a number of studies have demonstrated that MDSCs play a key regulatory role in many clinical diseases. In light of these studies, this review discusses the origin of MDSCs, the mechanisms underlying their activation, their role in a variety of clinical diseases, and their function in immune response regulation.
Seongje Cho;In-Young Yoon;Ji Soo Kim;Minji Lee;Hye Youn Park
Korean Journal of Psychosomatic Medicine
/
v.31
no.1
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pp.19-24
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2023
Objectives : Biofeedback is a useful non-pharmacological treatment for panic disorder (PD), but no studies have identified physiological markers related to the treatment response. This study investigated predictors of the treatment response for biofeedback in patients with PD. Methods : A retrospective study based on the electronic medical records of 372 adult patients with PD was performed. Patients received biofeedback treatment at least once, and physiological markers including heart rate, heart rate variability, respiratory rate, skin conductance, skin temperature, and electromyography were collected before the treatment began. The patients were classified as responders or non-responders based on the change in Clinical Global Impression-Severity (CGI-S) score. Results : The response rate to biofeedback treatment was 30.4%. Multivariable logistic regression analysis revealed that a higher CGI-S score at baseline and fewer benzodiazepine prescriptions were associated with a better response to biofeedback treatment. According to subgroup analyses, the baseline CGI-S score, dose of benzodiazepines, and skin conductance are candidate predictors of the response to biofeedback treatment in men, while only baseline disease severity was associated with the treatment response in women. Conclusions : The present results suggest that skin conductance may be target marker and predictor for biofeedback in male patients with PD.
Purpose : This study was to examine a correlation of response AC/A ratio by additional spherical powers with PD(Pupilary distance) and relative accommodation, and was to investigate correlation of CA/C ratio by prism powers. The mean differences between a reciprocal response AC/A ratio and a CA/C ratio were compared, and were suggested to be used as data in the refractive power and prism prescriptions in the clinical. Methods: The open field autorefractometer (Nvision-K 5001, Shin nippon) and Howell target at 40 cm fixation distance to 62 persons with average $22.62{\pm}2.84$ ages were used to measure the response AC/A ratio according to additional Spherical powers. The CA/C ratios were measured using the DOG card at 40cm according to prism powers. Results: When the response accommodation according to Additional Spherical power changes and the response accommodation according to prism power changes were compared, it was larger than the response accommodation according prism power change. These were significant differences statistically. The correlation of response AC/A ratio and PD is showed as r = -0.158, the CA / C ratio is shown as r = 0.093. The correlation of response AC/A ratio and relative accommodation showed as r = -0.253, the CA/C ratio showed as r = 0.566 that is predictable correlation. The correlation of response AC/A ratio and CA/C ratio showed as r = -0.355 that is low minus correlation (p = 0.000). The difference between a reciprocal response AC/A ratio and a CA/C ratio showed $0.12{\pm}0.06D/{\Delta}$ with a significant difference statistically (p=0.000). Conclusions: The correlation of relative accommodation and CA/C ratio showed that depend on the individual, The more a relative accommodation is, the higher a response accommodation of convergence by convergence stimulus is. The reciprocal response AC/A and CA/C ratio showed significant differences statistically. This can have higher CA/C ratio in patients with low AC/A ratio in clinical as an independent variable. Thus when the abnormal binocular vision was prescribed in the clinical, it is necessary to consider the accommodative response even if the AC/A ratio is a normal range.
Purpose. The purpose of this study was to identify the clinical variables that predict functional and cognitive recovery at 1- and 6-month in both severe and moderate/mild traumatic brain injury patients. Methods. The subjects of this study were 82 traumatically brain-injured patients who were admitted to a Neurological Intensive Care Unit at a university hospital. Potential prognostic factors included were age, motor and pupillary response, systolic blood pressure, heart rate, and the presence of intracranial hematoma at admission. Results. The significant predictors of functional disability in severe traumatic brain injury subjects were, age, systolic blood pressure, the presence of intracranial hematoma, motor response, and heart rate at admission. In moderate/mild traumatic brain injury patients, motor response, abnormal pupil reflex, and heart rate at admission were identified as significant predictors of functional disability. On the other hand, the significant predictors of cognitive ability for severe traumatic brain injury patients were motor response and the presence of intracranial hematoma at admission, whereas those for moderate/mild patients were motor response, pupil reflex, systolic blood pressure at admission, and age. Conclusions. The results of the present study indicate that the significant predictors of TBI differ according to TBI severity on admission, outcome type, and outcome measurement time. This can be meaningful to critical care nurses for a better understanding on the prediction of brain injury patients. On the other hand, the model used in the present study appeared to produce relatively low explicabilities for functional and cognitive recovery although a direct comparison of our results with those of others is difficult due to differences in outcome definition and validation methods. This implies that other clinical variables should be added to the model used in the present study to increase its predicting power for determining functional and cognitive outcomes.
Objective : Tension-type headache is the most common headache. The objective of this study is to find the clinical manifestation of tension-type headache and correlation with autonomic bioelectric response. Methods : This observation was carried out on 60 patients with tension-type headache. We used headache questionnaire and the Autonomic Bioelectric Response recoder(ABR-2000) for this study. Results : 1. Distribution of sex & age : male : female=5 : 7, 50s&60s group (28.3%) 2. Duration of onset : over 5years(50%), over one years(83.4%) 3. Causes of illness : stress(58.3%), severe fatigue(53.5%), tension(33.3%) 4. Time of attack : irregular(56.7%), day time(16.7%) 5. Pattern of pain: heavy(31 people), stiffness of occipital region (27 people) tightening around the head(25 people) 6. Curve : 40%, 56.7%, 35.0% SL(Slope low) at peak 1, 2, 3/ SH&SI not found 7. Regulation : 16.7% RR(Regulation reverse) at peak 1, 25% RH(Regulation high) at peak 2, 15% RR(Regulation reverse) at peak 3 8. Graph : Activity-60.0%, 70.0%, 63.3% lowered reaction(L, LR, L!) at peak 1, 2, 3 Reactivity-83.3%, 95.0%, 93.3% lowered reaction at peak 1, 2, 3 Conclusion : We find tension-type headache has remarkable relativeness with autonomic bioelectric response.
Objective: Evaluation and assessment of response rate, duration and toxicity in patients subjected to 5-FU based chemotherapy. Background: The therapeutic ratio shifts with different 5FU/LV regimens and none yet serve as the internationally accepted Gold Standard. A bimonthly regimen of high dose leucovorin is reported to be less toxic and more effective than monthly low dose regimens. We here compare therapeutic responses and survival benefit of the two regimens in poor prognosis patients with advanced colorectal carcinoma. Patients and Methods: A total of 35 patients with histologically confirmed colorectal carcinoma were subjected to de Gramont and Mayo Clinic regimen. Nineteen patients were treated with high dose folinic acid ($200mg/m^2$), glucose 5%, 5-FU ($400mg/m^2$) and 22 hr. CIV ($600mg/m^2$) for two consecutive days every two weeks. These patients had failed responses to previous chemotherapy and were above sixty years of age with poor general status. Sixteen patients (six below 60 years) with progressive disease were subjected to low dose folinic acid ($20mg/m^2$)for five days, 5FU($425mg/m^2$) injection bolus for 5 days, every five weeks. An initial evaluation was made in sixty days and responders were reevaluated at sixty days interval or earlier in case of clinical impairment. Based on positive prognosis, the therapy was continued. Evaluation of treatment response was made on the basis of WHO criteria. Results: The response rate was 44% in thirty four evaluable patients, with 4 complete responses (11.8%) and 11 (32.4%) partial responses. The two schedules were well tolerated, whereas, mild toxicity without WHO Grade ${\geq}2$ events was assessed. The response duration was extended (12 months) in a few patients with age above sixty years treated by high dose bimonthly regimen of 5FU/LV. Conclusion: The regimens are safe and effective in advanced colorectal carcinoma patients with poor general status.
Wang, Zhe;He, Mao-Lin;Zhao, Jin-Min;Qing, Hai-Hui;Wu, Yang
Asian Pacific Journal of Cancer Prevention
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v.14
no.5
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pp.2753-2758
/
2013
Various studies examining the relationship between Ezrin overexpression and response to chemotherapy and clinical outcome in patients with osteosarcoma have yielded inconclusive results. We accordingly conducted a meta-analysis of 7 studies (n = 318 patients) that evaluated the correlation between Ezrin and histologic response to chemotherapy and clinical prognosis (death). Data were synthesized in receiver operating characteristic curves and with fixed-effects and random-effects likelihood ratios and risk ratios. Quantitative synthesis showed that Ezrin is not a prognostic factor for the response to chemotherapy. The positive likelihood ratio was 0.538 (95% confidence interval [95% CI], 0.296- 0.979; random-effects calculation), and the negative likelihood ratio was 2.151 (95% CI, 0.905- 5.114; random-effects calculations). There was some between-study heterogeneity, but no study showed strong discriminating ability. Conversely, Ezrin positive status tended to be associated with a lower 2-year survival (risk ratio, 2.45; 95% CI, 1.26-4.76; random-effects calculation) with some between-study heterogeneity that disappeared when only studies that employed immunohistochemistry were considered (risk ratio, 2.97; 95% CI, 2.01- 4.40; fixed-effects calculation). To conclude, Ezrin is not associated with the histologic response to chemotherapy in patients with osteosarcoma, whereas Ezrin positivity was associated with a lower 2-year survival rate regarding risk of death at 2 years. Expression change of Ezrin is an independent prognostic factor in patients with osteosarcoma.
Objective : The Histoculture Drug Response Assay (HDRA), which measures chemosensitivity using minced tumor tissue on drug-soaked gelfoam, has been expected to overcome the limitations of in vitro chemosensitivity test in part. We analyzed interim results of HDRA in malignant gliomas to see if the test can deserve further clinical trials. Methods : Thirty-three patients with malignant gliomas were operated and their tumor samples were examined for the chemosensitivity to 10 chosen drugs by HDRA. The most sensitive chemotherapy regimen among those pre-established was chosen based on the number of sensitive drugs or total inhibition rate (IR) of the regimen. The response was evaluated by 3 month magnetic resonance image. Results : Among 13 patients who underwent total resection of the tumor, 12 showed no evidence of disease and one patient revealed progression. The response rate in 20 patients with residual tumors was 55% (3 complete and 8 partial responses). HDRA sensitivity at the cut-off value of more than one sensitive drug in the applied regimen showed a sensitivity of 100%, specificity of 60% and predictability of 70%. Another cut-off value of >80% of total IR revealed a sensitivity of 100%, specificity of 69%, and predictability of 80%. For 12 newly diagnosed glioblastoma patients, median progression-free survival of the HDRA sensitive group was 21 months, while that of the non-sensitive group was 6 months ($p$=0.07). Conclusion : HDRA for malignant glioma was inferred as a feasible method to predict the chemotherapy response. We are encouraged to launch phase 2 clinical trial with chemosensitivity on HDRA.
Park, Hae-Kwan;Jang, Kyung-Sool;Lee, Kyung-Jin;Rha, Hyung-Kyun;Joo, Won-Il;Kim, Moon-Chan
Journal of Korean Neurosurgical Society
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v.39
no.3
/
pp.183-187
/
2006
Objective : Hemifacial spasm has characteristic and specific electrophysiological finding, lateral spread response[LSR]. We study the correlation between change of lateral spread response during microvascular decompression[MVD] and clinical outcome after MVD. Methods : Sixty two patients with hemifacial spasm who were treated with microvascular decompression from March 2000 to February 2003 were included in this study. The monitoring of intraoperative facial electromyography[EMG] and brain stem auditory evoked potential were performed. Results : In 28 [44.7%] patients, there was persistence of lateral spread response after vascular decompression in root exit zone of facial nerve. Among these 28 patients, 9 had mild hemifacial spasm at discharge. Three out of 34 patients who had intraoperative disappearance of lateral spread response after MVD had mild hemifacial spasm. But Both groups, disappearance of LSR [Group I], and persistence [Group II] had only 2 patients with mild hemifacial spasm, and 5 patients at 3 months, respectively. Conclusion : Although intraoperative EMG monitoring is very useful in assessing the efficacy of MVD, the clinical outcome of MVD in patient with hemifacial spasm does not always correlate with EMG finding. The prognostic value of intraoperative LSR monitoring in the long-term results is questionable.
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