Clinical efficacy in 23 advanced solid tumor patients experiencing immune-related adverse events after treatment with immune checkpoint inhibitors / 中华微生物学和免疫学杂志

Objective:To observe the baseline characteristics and clinical efficacy in cancer patients who were treated with immune checkpoint inhibitors (ICIs) and experienced immune-related adverse events (irAEs).Methods:The clinical efficacy in cancer patients experiencing irAEs was retrospectively analyzed, and the objective response rate, progression-free survival, and overall survival were evaluated.Results:The median onset time of irAEs in 23 patients was 3.17 months. There were 47.8% (11/23) patients with multi-system irAEs, 63.3% (7/11) of which were non-simultaneous. The most common irAEs were immune-related pneumonia, hypothyroidism and immune-related liver dysfunction. Complete remission, partial remission and stable disease were respectively achieved in 0, 10 and 11 cases, while the other two patients developed progressive disease. The objective response rate was 43.5% and the disease control rate was 91.3%. With a median follow-up period of 16.5 months, 17 patients (73.9%) had progressive disease and the median progression-free survival was 9.63 months. Eight patients (34.8%) died before reaching the median overall survival. The progression-free survival and overall survival of patients with irAEs ≥grade 3 were significantly shorter than those with irAEs of grade 1-2 ( P<0.01). Conclusions:The occurrence of irAEs might correlate with the short-term efficacy and clinical benefits in patients treated with ICIs.

Impact of Lymphocyte Subsets on Chemotherapy Efficacy and Long-term Survival of Patients with Advanced Non-small-cell Lung Cancer / 中国医学科学院学报

Objective To analyze the impact of lymphocyte subsets on chemotherapy efficacy and long-term survival of patients with advanced non-small cell lung cancer(NSCLC).Methods Totally 125 NSCLC patients who had received first-line chemotherapy including paclitaxel and pemetrexed with/without platinum were enrolled in this study.Lymphocytes from peripheral blood were collected before and after two cycles of first-line chemotherapy.Flow cytometry was performed to determine the expressions of 21 fluorescence-labeled lymphocyte subsets.Based on the imaging findings,chemotherapy efficacy was evaluated,and impact of the lymphocyte subsets on progression-free survival(PFS)and overall survival(OS)were analyzed.Results The baseline peripheral lymphocyte subsets showed no significant difference among groups receiving different treatment protocols(all P>0.05).After 2 cycles of chemotherapy,the percentage of CD4CD29lymphocytes was(16.87±5.28)% in progressive disease group,which was significantly lower than those in complete remission+partial remission group [(22.42±7.88)%,P=0.013] and stable disease group [(21.88±6.81)%,P=0.009].The median PFS was 7.07 months and median OS was 23.00 months.Cox multivariable regression analysis showed that the percentages of HLA-DR(HR:1.03,95%CI:1.01-1.05,P<0.001) and CDHLA-DRlymphocytes (HR:1.05,95%CI:1.01-1.08,P<0.001)were positively correlated with OS.Conclusions The rise of CD4CD29T lymphocytes in patients after chemotherapy indicates good chemotherapy efficacy.Higher percentage of HLA-DRand CD3HLA-DRlymphocytes in peripheral blood before chemotherapy predicts favorable prognosis.

Prognostic significance of tumor-infiltrating CD8⁺ or CD3⁺ T lymphocytes and interleukin-2 expression in radically resected non-small cell lung cancer / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Altered immunoresponse is associated with tumorigenesis and cancer progression. This study assessed the levels of tumor-infiltrating CD3 + or CD8 + T lymphocytes and interleukin-2 (IL-2) protein in radically resected non-small cell lung cancer (NSCLC) tissues to predict overall survival (OS) of the patients.</p><p><b>METHODS</b>Paraffin-embedded tissue specimens from 129 NSCLC patients were retrospectively collected for immunostaining of CD8 + , CD3 + , and IL-2 expression. Clinicopathological and survival data were collected and analyzed using the Chi-squared test, Kaplan-Meier curves, and the log-rank test or the Cox regression model.</p><p><b>RESULTS</b>The data showed a significant inverse association between CD8 + T lymphocyte levels and IL-2 expression (r = -0.927; P = 0.000) and between the levels of CD8 + and CD3 + T lymphocytes (r = -0.722; P = 0.000), but a positive association between CD3 + T lymphocyte levels and IL-2 expression (r = 0.781; P = 0.000) in NSCLC tissues. Furthermore, the levels of CD3 + and CD8 + T lymphocytes and IL-2 expression were associated with tumor stage (P = 0.023, 0.006, and 0.031, respectively) and the level of CD8 + T lymphocytes was associated with the patient gender (P = 0.024). In addition, the levels of CD8 + T lymphocytes were associated with an unfavorable 5-year OS, whereas patients with high levels of CD3 + T lymphocytes in tumor lesions and IL-2-expressing tumors had significantly better 5-year OS rates than patients with low levels.</p><p><b>CONCLUSIONS</b>The levels of CD8 + T cells in tumor lesions and IL-2 expression were both independent predictors of OS for these NSCLC patients. Thus, the detection of tumor-infiltrating CD3 + or CD8 + T lymphocytes and IL-2 expression could be useful to predict the prognosis of radically resected NSCLC patients.</p>

A proliferation-inducing ligand expression in breast cancer and its relationship with prognosis / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the relationship between a proliferation-inducing ligand (APRIL) expression in primary tumor foci of breast cancer and the patients' prognosis.</p><p><b>METHODS</b>Paraffin sections of surgical specimens were retrospectively collected from 130 stage I-III breast cancer patients who received surgery between January 2000 and December 2002 in our hospital. Immunohistochemistry was used to assess APRIL expression intensity in the tumor cells and density of interstitial APRIL-positive cells, and their association was analyzed with the density of interstitial CD4⁺ and CD8⁺ cells and with the histopathologic features, overall survival (OS), and disease-free survival (DFS) of the patients.</p><p><b>RESULTS</b>APRIL positive staining was found in the cytoplasm of the tumor cells, interstitial cells, and the extracellular matrix. APRIL intensity in the tumor cells was positively correlated with the density of interstitial APRIL-positive cells (P=0.009) and Ki67 (P=0.003). The density of interstitial APRIL-positive cells was positively correlated with the density of interstitial CD4⁺ cells (P<0.001) and CD8⁺ cells (P<0.001). In hormone receptor negative patients (ER- and PR-), multivariate COX regression identified the density of interstitial APRIL-positive cells as a positive prognostic factor for DFS (HR=0.313, 95% CI=0.107-0.920, P=0.035). CONCLUSIONSl APRIL is widely expressed in the interstitial immune cells in breast cancer. APRIL staining intensity in the tumor cells is positively correlated with tumor proliferation, indicating that the immune cells might promote tumor proliferation by secreting APRIL. A greater density of interstitial APRIL-positive cells is associated with a good prognosis in hormone receptor-negative patients.</p>

Clinical efficacy observation of cetuximab combined with chemotherapy in the treatment of metastatic colorectal carcinoma / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To observe the clinical efficacy of cetuximab plus chemotherapy in the treatment of metastatic colorectal carcinoma.</p><p><b>METHODS</b>Clinicopathological data of 128 patients with metastatic colorectal cancer admitted in the Department of Oncology, Chinese PLA General Hospital from 2008 to June 2012 were analyzed retrospectively. Among them, 91 patients received cetuximab as the first-line therapy and 37 in the second-line or more-line therapy. The chemotherapy regimens included oxaliplatin-based therapy (FOLFOX/XELOX), irinotecan-based therapy (FOLFIRI/XELIRI) and fluorouracil-based therapy (Xeloda). The efficacy was evaluated according to RECIST 1.0 criteria. The remission rate, control rate and time to disease progression were compared among patients receiving cetuximab combined with different chemotherapy regimens in different periods.</p><p><b>RESULTS</b>The disease control rate of cetuximab applied in the first-line treatment was higher than that of the second-line or more-line [85.9% (61/71) vs. 59.3% (16/27), P=0.004]. The disease control rate of the group treated with cetuximab plus oxaliplatin-based chemotherapy was much higher compared to the other two groups [91.1% (41/45) vs. 68.1% (32/47), 4/6, P=0.021]. But there were no significant differences among three regimens in the terms of overall response rate (all P>0.05). The median time to progression of groups with cetuximab plus irinotecan, oxaliplatin or capecitabine was 7.8 months, 8.5 months and 5.2 months respectively. The median time to progression of cetuximab combined with chemotherapy in the first-line treatment and the second-line or more-line was 8.2 and 7.7 months respectively. However, the differences were not statistically significant (P>0.05).</p><p><b>CONCLUSIONS</b>Cetuximab in combination with oxaliplatin-based chemotherapy is recommended as the first-line application in the treatment of metastatic colorectal carcinoma patients, because it is helpful to improve the rate of disease control.</p>

Analysis of the clinical characteristics and treatment of primary gastric choriocarcinoma / 中国肿瘤临床

Objective:Primary gastric choriocarcinoma (PGC) is a rare tumor. This study aimed to analyze cases reported in Chi-nese and two cases in our hospital. This study was also conducted to investigate the clinical characteristics and treatment of PGC. Meth-ods:The Chinese Medical Current Contents and China Biology Medicine database was retrieved with the following terms:primary gas-tric choriocarcinoma, stomach choriocarcinoma, and ectopic choriocarcinoma. The clinical data in published literature were retrospec-tively analyzed. Two cases from our hospital were also retrospectively analyzed. Results:A total of 16 patients with PGC (14 case stud-ies and 2 cases from our hospital) were included in this study. The average age of the patients was 57.69 years (ranging from 42 years to 79 years). Among the 16 patients, 4 were females and 12 were males. The main clinical manifestation was abdominal discomfort (12/16). Laboratory and imaging tests were non-specific, but HCG-βin all of the patients increased (11/11). Organ or lymph node metasta-sis was found in 13 patients, including 6 cases in which two or more organs showed metastasis. These organs were primarily the liver, the stomach lymph nodes, the lungs, the brain, and the abdominal cavity. Pathological examination results showed that 12 of the 16 cas-es displayed ulcers with necrosis and hemorrhage. The four remaining cases manifested lesions. Lesions may occur in the stomach less-er curvature (5 cases), stomach sinus (6 cases), cardiac (2 cases), and gastric body (3 cases). The histological components of PGC co-ex-isted with other factors, such as adenocarcinoma (7 cases), adenocarcinoma and squamous (2 cases), adenocarcinoma and a signet ring cell (1 case), or pure choriocarcinoma (6 cases). Surgery combined with chemotherapy was the main treatment. A total of 14 patients un-derwent surgical operations. Among these patients seven underwent chemotherapy after surgery and one underwent chemotherapy. Among the 10 patients who were followed up, 8 died within six months after diagnosis. Conclusion:PGC is a rare stomach cancer with poor prognosis and primarily affects older men. No characteristic clinical manifestations were observed, but HCG-βas a specific serum tumor biomarker increased in all of the affected patients. Histological components co-existed with other stomach cancers. Surgical exci-sion combined with chemotherapy was the preferred treatment in early stages, and systemic chemotherapy was the recommended treat-ment in advanced stages.

Relevance theories about tumor stem cells and occurrence and metastasis of tumors:recent progress / 军事医学

Tumor stem cells (TSCs) are a group of cells which have self-renewal and differentiation potential in tumor tissues.TSCs not only play an important role in the occurrence and development in tumors , but also are closely related to tumors′invasion,metastasis,heterogeneity and chemo-resistance.Further research of TSCs has become a hot spot .This review intends to explain the formation of TSCs ,the relationship between TSCs and the microenvironment , as well as the model of the TSC microenvironment .Signalling pathways and regulatory factors of TSCs are also discussed .

Prognostic value of B lymphocyte infiltration in breast cancer / 南方医科大学学报

<p><b>OBJECTIVE</b>To assess the prognostic value of CD20(+) tumor-infiltrating lymphocytes (TILs) in early-stage breast cancer.</p><p><b>METHODS</b>Paraffin sections were collected from 130 cases of stage I-III breast cancer undergoing surgery between January, 2000 and December, 2002 in our hospital. Immunohistochemistry was used to analyze mesenchymal CD20(+) TILs infiltration in the tumor and evaluate its association with the density of CD4(+) and CD8(+) TILs. The association of CD20(+) TILs was evaluated with the histopathologic features, overall survival (OS), distant disease-free survival (DDFS), and disease-free survival (DFS) of the patients.</p><p><b>RESULTS</b>Aggregations of CD20(+) lymphocytes were observed in 37.69% (49/130) of the cases. CD3(+) T cells were found to aggregate around CD20(+) B cell aggregations to form lymphoid follicle-like structures. The aggregations of CD20(+) TILs were positively correlated with the densities of mesenchymal CD8+ and CD4(+) TILs. Overall, CD20(+) TIL aggregations were not significantly correlated with the outcomes of the patients, but multivariate COX regressions suggested that CD20(+) TIL aggregations were positively correlated with DDFS (HR=0.251, 95% CI=0.071-0.894, P=0.033) and OS (HR=0.325, 95% CI=0.103-1.028, P=0.056) in hormone receptor-negative patients but not in the positive patients. Further analysis suggested that post-operative adjuvant endocrine therapy significantly improved the OS of patients positive for hormone receptors without CD20(+) TIL aggregations (P=0.001).</p><p><b>CONCLUSION</b>The long-term therapeutic effects of adjuvant endocrine therapy are correlated with CD20(+) TIL aggregations to affect prognostic value of CD20(+) TIL aggregations in early-stage breast cancer patients.</p>

Clinical significance of detecting peripheral blood T lymphocyte subsets in patients with pulmonary adenocarcinoma / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the clinical value of T lymphocyte subsets in prediction of chemotherapy responses of patients with pulmonary adenocarcinoma.</p><p><b>METHODS</b>Fifty-five chemotherapy-naive patients with pathologically or cytologically confirmed pulmonary adenocarcinoma were examined for peripheral blood T lymphocyte subsets using flow cytometry, including CD3(+) T cells, CD3(+)CD4(+) T cells, CD3(+)CD8(+) T cells, CD45RO(+) T cells and CD45RA(+) T cells.</p><p><b>RESULTS</b>Patients who responded favorably to chemotherapy (CR(+)PR) showed a significantly lower percentage of CD45RA(+) T cells than those who failed to respond to chemotherapy (P=0.04). CD45RO(+) T cell percentage were slightly higher in the response group than in the non-response group, but this difference was not statistically significant (P=0.25). The other T cell subsets, namely CD3(+), CD3(+)CD4(+), and CD3(+)CD8(+) T cells showed no significant differences between the two groups.</p><p><b>CONCLUSION</b>A high percentage of peripheral blood CD45RA(+) T cells is associated with a poor short-term outcome of chemotherapy in patients with advanced pulmonary adenocarcinoma. Peripheral blood CD45RA(+) T cell level can be a reliable index for predicting chemotherapy efficacy in these patients.</p>

Percutaneous cryoablation of cervical lymph node metastases under ultrasonic guidance / 中国耳鼻咽喉头颈外科

OBJECTIVE To observe the feasibility and safety of cryoablation of cervical lymph node metastases for nonsurgical candidates.METHODS The procedure was performed after achievement of local anesthesia for 15 cases.In this clinical study,local anesthesia with no sedation was performed to all the patients.In all cases,patients underwent two freeze/thaw cycles.RESULTS Tumors of 14 patients were thoroughly covered by ice balls.In one patient,96% of the tumorous lesion was covered by ice balls.In these patients,no complicated complication was observed during the treatment.CONCLUSION Percutaneous cryoablation therapy for cervical lymph node metastases under ultrasonic guidance is a feasible and minimally invasive method with satisfactory local control.

Clinical study on the effect of Yangyinjiandu decoction on acute raditation esophagitis / 中华放射肿瘤学杂志

Objective To investigate the effect of Yangyinjiandu decoction for acute radiation esophagitis.Methods Lung cancer and mediastinal tumor treated by radiotherapy(portals including oesophagus to a radical tumoricidal dose≥40Gy, with≥10cm oesophagus include in radiotherapy).Patients were randomly divided according to the time of acceptance into the treatment group and the control group.All parameters of the two groups were basically similar and comparable.The treatment group was given Yangyinjiandu decoction(one dose daily,water decoction,200ml,twice a day) taken in the morning and in the evening before the end of radiotherapy.The control group was given oral vitamin C tablet 100mg once a day before the end of radiotherapy.Five days after radiotherapy,the control group took oral prednisone 5mg three times a day and amoxicillin 5g three times a day.All the above medicines were continued for 7 days.Results The commencement of complication was 14.86?0.34 days in the treatment group and 13.55?0.26 days in the control group(P

Experiment of advancing chemosensitization of Etoposide by insulin in vitro / 中国临床药理学与治疗学

AIM:To investigate the effects of insulin on drug sensitivity of Etoposide(Vp-16) to MBA-MD-543(human breast cancer cell line) in vitro.METHODS:Insulin was applied directly to the MBA-MD-543 cultured in vitro.The effects of insulin and Vp-16 on the number of viable cell,the total number of cells were assayed by MTT method and cell count.RESULTS: Insulin could induce the cell growth and promote the cell metabolism at the concentration(4.0)-(32.0)(mU?ml~(-1))(8-18 hours).At the condition of same density of cells,the administration of insulin((7.5)(mU?ml~(-1))) before adding Vp-16 in 9-15 h,enhanced the chemocytotoxity of Vp-16((70.09)(?g?ml~(-1))) on human breast cancer cells as indicated by MTT colorimetry.CONCLUSION: Proliferation of human breast cancer cell line can be induced by insulin,and insulin can sensitize MBA-MD-543 to the anticancer activity of Vp-16 in vitro. The key of improving the chemotherapeutic effect is the selection of revulsant occasion and concentration.It is possible to increase the growth and metabolism of cancer cells first so as to enhance the chemosensibility,and then administer chemotherapeutic agents,thus improving their theraeutic effects.

Research on the Effect of Kanglaite Injection on Enchancing Lung Cancer Cell' s Sensitivity to TXT Injection / 中药新药与临床药理

Objective To investigte the inhibit effects of drug combination of Kanglaite injection(KLT) and TXT on human pulmonary epithelial cells(95D) in vitro,and to find the best time of combination.Method 95D cell growth inhibition was measured with MTT assay.Results Various concentration of KLT and TXT could inhibit the proliferation of 95D cell,and KLT could enchance the sensiti vity of 95D cell to TXT(P

Effects of GWe on the sIL-2R levelsl in chronic persistent hepattis patients / 中国免疫学杂志

The level of serum soluble interleukin 2 receptor(sIL-2R)was studied in 29chronic persistent hepatitis (CPH) patients and in 18 normal individuals.It was found that sIL-2R level was significantly higher in the CPH patients than that in normal individuals(P

Inhibitory effect of ibandronate on the growth of lung cancer cell line PLA-801D in vitro / 解放军医学杂志

Objective To study the inhibitory effect of ibandronate(IBN)on the growth of lung cancer cell line PLA-801D in vitro,and the mechanism of such effect was studied.Methods The effects of different doses or treatment time of IBN on the growth of PLA-801D cell line were detected by MTT method.The mechanism of the effect was analyzed by the examination of cell cycle using flow cytometry.Results With the concentration of 10 to 100 ?g/ml,IBN obviously inhibited the growth of PLA-801D cell(P