Research Advances of Immunotherapy for Follicular Lymphoma --Review / 中国实验血液学杂志

Follicular lymphoma is an indolent malignant tumor originating from lymph nodes and lymphoid tissues, which may affect the patients' quality of survival due to the recurrence and progression. In recent years, with the deepening understand of the molecular biology and signaling pathways, many new targeted drugs for follicular lymphoma have been discovered, such as monoclonal antibodies, checkpoint inhibitors, epigenetic regulation related targeted therapies and signaling pathway inhibitors. In this review, the new progress of immunotherapy for follicular lymphoma is summarized briefly.

Clinical Significance of EBV-DNA Copy Number in EBV Positive Lymphoma Patients / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of EBV-DNA copy number on the prognosis of patients with EBV positive lymphoma.@*METHODS@#Clinical data of 109 patients diagnosed as EBV positive lymphoma in Tianjin Medical University Cancer Institute and Hospital from January 2010 to January 2020 were enrolled and analyzed retrospectively. Kaplan-Meier analysis was used for survival analysis, Log-rank was used to compare the clinical characteristics between the patients in different groups, and Cox regression was used for multivariate analysis.@*RESULTS@#Among the 109 patients with EBV-positive lymphoma, the medium age were 56 (range 15 to 83) years old. 29 patients at Ann Arbor stage I-II while 80 patients at stage III-IV. The average value of EBV-DNA was 1 023 510 IU/ml, 7 patients were higher than the average value, while 102 patients were lower. KM survival analysis showed that OS and PFS in patients with EBV-DNA above average level were shorter than those in patients with EBV-DNA below average level (OS: P=0.048, PFS: P=0.001), EBV-DNA copy number was a factor affecting the prognosis of patients. In addition, LDH level showed positive correlation with EBV-DNA copy number (r=0.650), which was also one of the factors affecting OS (P=0.053).@*CONCLUSION@#EBV-DNA copy number and LDH level can influence the prognosis of EBV positive lymphoma patients. Therefore, detection of EBV-DNA copy number in peripheral blood is important for evaluate the prognosis the patients.

Research Progression of Subcutaneous Panniculitis-like T-Cell Lymphoma--Review / 中国实验血液学杂志

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a very rare cutaneous malignant lymphoma derived from cytotoxic T cells that mainly involves subcutaneous adipose tissue rather than epidermis and dermis. It usually occurs in young and middle-aged population, and the etiology is currently unclear. Clinically, SPTCL is characterized by subcutaneous plaques, nodules, and skin ulcers with swell and ache, mainly presenting in limbs and trunk. SPTCL has been restricted to cases that express α/β phenotype, whereas cases with γ/δ phenotype are categorized to cutaneous γ/δ

Preparation of multifunctional nanoparticles targeting tongue cancer and in vitro study / 华西口腔医学杂志

<p><b>OBJECTIVE</b>This study aims to prepare docetaxel (DOC)-loaded multifunctional nanoparticles containing indocyanine green (ICG) and perfluorohexane (PFH) as targeted drug delivery system, which is supplemented with stromal cellderived factor-1 (SDF-1), and characterize their properties.</p><p><b>METHODS</b>Multifunctional nanoparticles were prepared by using the double emulsion method. SDF-1 was covalently conjugated to the surface of the nanoparticles through thioether bonding. Their particle size, distribution, and surface potential were determined with the Malvern measuring instrument. The conjugation of SDF-1 was evaluated by confocal laser scanning microscope. Encapsulation efficiency (ELC), drug loading capacity (DLC), and release regularity of the nanoparticles were determined by high-performance liquid chromatography (HPLC). In vitro photothermal property was recorded by a thermal imager. The in vitro imaging capacity was observed by a photoacoustic instrument and an ultrasonic diagnostic apparatus. Targeting capability was assessed by flow cytometry. The cell activity on SCC-15 cells was checked by CCK-8 method.</p><p><b>RESULTS</b>The targeted multifunctional nanoparticles showed regularly sphericity. The diameter was (502.88±17.92) nm. The zeta potential was (-11.5±3.15) mV. ELC was 54.12%±1.74%. DLC was 1.08 mg·mL-1. In vitro drug release was initially fast and subsequently slow. The photothermal characteristics were related to the concentration; the higher the concentration, the higher the temperature. Nanoparticles could detect significant photoacoustic and ultrasound signals. The in vitro targeting rate was 89.99%. No significant differences of cell viability in the SINPs groups were observed at each concentration (P>0.05). The inhibition effect of DOC-SINPs was stronger than that of SINPs whether or not in the presence of laser irradiation among the groups of 150 and 200 μg·mL-1 (P<
0.05).</p><p><b>CONCLUSIONS</b>Multifunctional nanoparticles for diagnosis and treatment were successfully prepared and displayed dualmode ultrasound/photoacoustic imaging and antitumor effects of chemotherapy and photothermal therapy.</p>

Expression and prognostic value of regulatory T cells and M2 macrophages in diffuse large B-cell lymphoma tissues / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the prognostic value of regulatory T cells (Tregs) and M2 macrophages in diffuse large B-cell lymphoma (DLBCL) tissues.</p><p><b>METHODS</b>The expression of CD163 and Foxp3 was detected by immunohistochemistry in 92 cases of DLBCL, and it was statistically analyzed whether their expressions correlate with clinical data and prognosis in patients with DLBCL.</p><p><b>RESULTS</b>The density of M2 macrophage and regulatory T cells in DLBCL tumor tissues was significantly higher than that in the adjacent tissues (P = 0.02, P = 0.04). The expression of M2 macrophages was significantly positively correlated with regulatory T cells expression (r = 2.012, P < 0.05). High density of M2 or Tregs had a relationship with extranodal involvement (P < 0.05). Cox regression analysis showed that the expressions of CD163 and Foxp3 were independent prognostic factors of DLBCL (P < 0.05).</p><p><b>CONCLUSIONS</b>Combined detection of the expression of CD163 and Foxp3 proteins and then evaluation of the amount of M2 macrophages and Tregs can be used to more closely predict the prognosis for DLBCL patients.</p>

Initial computed tomography findings of invasive pulmonary aspergillosis in non-hematological patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The computed tomography (CT) findings of invasive pulmonary aspergillosis (IPA) are unclear in non-hematological patients. The present study was a retrospective evaluation of CT images in non-hematological patients with IPA.</p><p><b>METHODS</b>All adult patients who met the 2008 European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria for proven or probable IPA were included during a 5-year study at our institutions. Initial CT findings in our cohort were retrospectively reviewed by two independent thoracic radiologists blinded to patient demographics and clinical outcomes. The presence, pattern, and distribution of abnormalities were recorded.</p><p><b>RESULTS</b>Twenty-three non-hematological patients with pathologically confirmed IPA were included in our study. Areas of ground-glass opacities were present in 14 patients (61%), which were bilateral in 10 patients and unilateral in four. This pattern mainly involved the middle and upper lung zones. Air-space consolidation was identified in 12 patients (52%), and the areas were distributed along the bronchus or subpleura in most cases. Other findings, including five small nodules (22%), three macronodules (13%), and one halo sign (4%), were less common.</p><p><b>CONCLUSIONS</b>CT findings of IPA in non-hematological patients frequently manifested as acute bronchopneumonia, and ground-glass opacities and air-space consolidations were the most common CT findings of IPA in these patients.</p>

Efficacy and survival status of retuximab-NCE regimen treatment in patients with relapsed or refractory B cell non-Hodgkin's lymphoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The aim of this study was to analyze the efficacy and toxicity of RNCE regimen in the treatment of relapsed or refractory B cell non-Hodgkin's lymphoma (NHL).</p><p><b>METHODS</b>From January 2000 to December 2005, 46 patients with relapsed or refractory B cell NHL were treated by RNCE regimen with or without radiotherapy for the involved field. The clinical characteristics, response, toxicity and long-term survival results were analyzed retrospectively.</p><p><b>RESULTS</b>A total of 46 patients were eligible. The complete response rate of second-line therapy was 52.17% (24/46), and the overall response rate was 82.61% (38/46). The median follow-up duration in this series was 69 months (range:6 to 102 months). The overall 1, 3, 5-year survival rate was 74.8%, 48.3%, 40.1%, respectively, with a median survival time of 30.2 months (5 to 65 months), and median progression free survival time of 10.9 months (2 to 31 months). The major toxicities were myelosuppression, GI toxicity, fatigue, fever and alopecia.</p><p><b>CONCLUSION</b>Our data show that RNCE regimen treatment is effective and well tolerated in patients with relapsed or refractory B cell non-Hodgkin's lymphoma.</p>

Expression of Cdc7 and mcm2 as a marker for proliferation and prognosis in diffuse large B cell lymphoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The aim of this study was to assess the expression of cell division cycle 7 (Cdc7) kinase and minichromosome maintenance protein 2 (MCM2) in diffuse large B cell lymphoma (DLBCL) and explore their relationship with prognosis of DLBCL patients.</p><p><b>METHODS</b>Clinical data of 60 DLBCL patients treated in our hospital from 2008.1 to 2010.1 were collected. The expression levels of Cdc7 and MCM2 in peripheral blood and bone marrow were determined by real-time PCR. A statistical analysis was carried out to evaluate their association with prognosis in DLBCL patients.</p><p><b>RESULTS</b>The 2-year survival rate of patients with high expression of peripheral blood Cdc7 was 38.3% and those with low expression 65.4% (P = 0.001). The 2-year survival rate of patients with high expression of bone marrow Cdc7 was 37.2% and those with low expression was 75.5% (P = 0.032). The 2-year survival rate of patients with high expression of MCM2 in peripheral blood was 44.0% and those with low expression was 68.2% (P = 0.025). The 2-year survival rate of patients with high expression of MCM2 in bone marrow was 39.0% and those with low expression was 63.4% (P = 0.007). A poor disease specific survival was observed in DLBCL patients with high level expression of Cdc7 and MCM2.</p><p><b>CONCLUSIONS</b>Cdc7 and MCM2 expression can be used to assess tumor proliferation and may be useful as an additional marker in combination with conventional markers in prediction of the outcome of DLBCL patients. Moreover, the Cdc7 and MCM2 signal pathway might be useful as a new approach in the treatment of refractory DLBCL lymphoma patients.</p>

Expression of excision repair cross-complementation gene in drug-resistant process of carboplatin administration in tongue squamous cell cancer (Tca8113) / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the correlations between the resistant degree of Tca8113 agaist carboplatin and the expression of excision repair cross-complementation 1 (ERCC-1).</p><p><b>METHODS</b>Tca8113 cells were exposed in the carboplatin solutions of gradually increasing concentration. Cancer cells were divided into six experimental groups and a control group. In the course of culture, the half inhibitory concentration (IC(50)) of each groups were detected by methyl thiazolyl tetrazolium (MTT). The expressions of ERCC-1 at mRNA and protein level were detected by reverse transcription polymerase chain reaction (RT-PCR) and Western blotting.</p><p><b>RESULTS</b>With the increase of drug resistance, the expression of ERCC-1 increased gradually at mRNA level (control group: 0.84 ± 0.06, group 1: 0.96 ± 0.06, group 2: 1.07 ± 0.11, group 3: 1.13 ± 0.09, group 4: 1.19 ± 0.08, group 5: 1.29 ± 0.07, group 6: 1.47 ± 0.08), values between neighboring or interval groups have significant differences (P < 0.05); the expression of ERCC-1 increased gradually at protein level (control group: 0.69 ± 0.05, group 1: 0.86 ± 0.04, group 2: 1.01 ± 0.04, group 3: 1.24 ± 0.09, group 4: 1.44 ± 0.14, group 5: 1.56 ± 0.19, group 6: 1.88 ± 0.22), values between neighboring or interval groups have significant differences (P < 0.05). The gradually increasing RT-PCR gray values were related to the gradually increasing IC(50) in all groups (r = 0.91, P < 0.01), and the gradually increasing western blotting gray values were also related to the gradually increasing IC(50) in all groups (r = 0.88, P < 0.01).</p><p><b>CONCLUSIONS</b>The high expression of ERCC-1 may become an indicator of Tca8113 resisting carboplatin. This might provide a potential target to reverse tongue squamous cell cancer (Tca8113) that has resistance to carboplatin.</p>

Nimotuzumab in combination with chemotherapy in patients with advanced non-small cell lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the role of nimotuzumab in combination with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>The clinical data of 37 NSCLC patients who received nimotuzumab in combination with chemotherapy in Tianjin Medical University Cancer Hospital from January 2009 to October 2010 were retrospectively reviewed. Of the thirty-seven patients, 12 patients were in stage III B, 25 patients in stage IV. Twenty-four patients recived platinum-based chemotherapy in combination with nimotuzumab, 13 patients recived nonplatinum-based chemotherapy in combination with nimotuzumab. Ten patients received nimotuzumab in combination with chemotherapy as first-line regimen, 23 patients as second-line regimen, 4 patients as third-line regimen.</p><p><b>RESULTS</b>Of the 37 advanced NSCLC patients who received nimotuzumab in combination with chemotherapy, the total number of chemotherapy were 137 cycles, the mean number was 3.7 cycles. One patient had complete remission (CR), 9 patients had partial remission (PR), 16 cases had stable disease (SD), and 11 patients had progressive disease (PD). The response rate (RR) was 27% and clinical benefit rate (CBR) was 70.3%. The main side effects were bone marrow suppression and gastrointestinal reactions. Grade I acneiform rash was found in one patient.</p><p><b>CONCLUSION</b>The regimen of nimotuzumab in combination with chemotherapy can improve the response rate and was well tolerated in patients with advanced non-small cell lung cancer.</p>

Capecitabine combined with weekly docetaxel in Chinese patients > 65 years with anthracycline-resistant metastatic breast cancer / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>There are no data on more tolerable capecitabine doses in elderly patients in Chinese population. The aim of this study was to evaluate the activity and safety of capecitabine combined with weekly docetaxel for the treatment of anthracycline-resistant metastatic breast cancer (MBC) in older Chinese patients.</p><p><b>METHODS</b>MBC patients aged > 65 years pretreated with 1 - 5 prior chemotherapy regimens, including an anthracycline, received oral capecitabine 825 mg/m(2) twice daily, days 1 - 14, plus docetaxel 30 mg/m(2) on days 1 and 8 every 21 days. All 41 enrolled patients received at least 1 dose of treatment and were evaluable for safety; 38 received at least 2 cycles (median 4, range 2 - 8) and were evaluable for efficacy.</p><p><b>RESULTS</b>The overall objective response rate was 47%, including complete responses in 8% of patients. Median time to progression was 8.9 months. Median overall survival was 17.6 months. The most common side effects were haematological and gastrointestinal toxicities and hand-foot syndrome. The only grade 3/4 adverse events were neutropenia (12%), alopecia (7%), grade 3 nausea and vomiting (2%) and grade 3 nail toxicity (2%).</p><p><b>CONCLUSIONS</b>Capecitabine 825 mg/m(2) twice daily plus weekly docetaxel is active with an acceptable safety profile in Chinese women > 65 years with anthracycline-resistant MBC. Efficacy and tolerability compare favourably with previously reported trials evaluating higher capecitabine doses in combination with 3-weekly or weekly docetaxel.</p>

Clinical characteristics and treatment analysis of primary breast lymphoma: 49 cases report / 中华外科杂志

<p><b>OBJECTIVE</b>To explore the morbidity, clinical characteristics, diagnosis, metastasis, treatment and prognosis of primary breast lymphoma (PBL).</p><p><b>METHODS</b>From January 1960 to August 2007, 49 cases with PBL were treated among 22811 cases of breast malignancy and 7337 cases of malignant lymphoma. The clinical data of these 49 patients, included gender, age, pathologic type, breast X ray and B ultrasound examination results, involved lymph nodes and organs, treatment, survival time, were retrospectively analyzed.</p><p><b>RESULTS</b>From 1960 to 2007, the incidence rate of PBL in Tianjin Municipality was 59/10 millions; in details, the incidence rate of PBL for every 10 years was 2/10 millions, 3/10 millions, 0, 13/10 millions and 32/10 millions, respectively. According to circle graph of age, PBL occurred frequently in female aged 30 to 59 years. Most of this group of PBL was non-Hodgkin lymphoma (48 cases). No typical characteristics was found with the examination of breast X ray, B ultrasound and frozen section pathology. Bone marrow (9 cases), lung (7 cases), meninges (4 cases) and ovary (4 cases) were frequently involved organs. The overall 5-year survival rate was 6.1% for the group. The prognosis in patients with radical mastectomy combined chemotherapy was much better than that in patient received super to local mastectomy plus chemotherapy or simple tumor resection plus chemotherapy (5-year survival rates were 21.4%, 0, 0, respectively).</p><p><b>CONCLUSIONS</b>PBL is a kind of rare lymphoma with incidence increasing sharply in the past few decades. The clinical manifestation is atypical. Diagnosis of PBL should adopt histological examination. Radical mastectomy combined chemotherapy could bring better prognosis, but the prognosis is still poor.</p>

Adaptive changes of ultrastructures of dentritic cells during maturation induced by lipopolysaccharide / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the adaptive changes of ultrastructure of the dentritic cells (DC) before and after maturation.</p><p><b>METHODS</b>The murine bone marrow mononuclear cells were induced into immatured dendritic cells with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). The cell morphology was observed under an inverted phase contrast microscope, and the surface markers were detected by flow cytometry. Then the DC was induced to be matured with lipopolysaccharide (LPS) for 48 hours, the ultrastructures of DC was observed before and after maturation under transmission electron microscope and then a comparative analysis was doned.</p><p><b>RESULTS</b>The surface processes of matured dentritic cells stimulated by LPS decreased significantly, whereas the organelles and the diameter of nucleolus increased.</p><p><b>CONCLUSION</b>The distribution of surface processes may be associated with the antigen-presenting capacity of DC, and it is also a potential ruler of cell function and status.</p>

DNCE regimen for treatment of refractory or relapsed aggressive and highly aggressive non-Hodgkin lymphoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of DNCE [DXM, navelbine (NVB), DDP and Vp-16] regimen and DICE [dexamethasone (DXM), ifosfamide (IFO), cisplatin (DDP) and etoposide (Vp-16)] regimen in the treatment of refractory or relapsed aggressive and highly aggressive non-Hodgkin lymphoma (NHL).</p><p><b>METHODS</b>A total of 69 patients with histopathologically proved advanced aggressive and highly aggressive NHL were randomized into trial group (32 patients treated with DNCE regimen) and control group (37 patients treated with DICE regimen). The control group was given DICE regimen: DXM 20 mg, iv d1 approximately d4; IFO 1 g/m2), iv d1 approximately d4; Mesna 400 mg, iv q8h, d1 approximately d4; DDP 25 mg/m2, iv d1 approximately d4; Vp-16 100 mg/m2, iv d1 approximately d4; one cycle for 21 approximately 28 days. The trial group was given DNCE regimen: DXM 20 mg, iv d1 approximately d4; NVB 25 mg/m2, iv d1 and d5; DDP 25 mg/m2, iv d1 approximately d4; Vp-16 100 mg/m2, iv d1 approximately d4; one cycle for 21 approximately 28 days. Each patient completed at least 2 cycles of treatment.</p><p><b>RESULTS</b>A better efficacy was shown in the complete response rate, partial response rate, and total response rate between DNCE and DICE groups (18.8% vs. 10.8%, 37.5% vs. 35.1%, and 56.3% vs. 45.9%, respectively), but the differences were statistically non-significant (P > 0.05). The 1-, 3-, and 5-year survival rates were not significantly increased in DNCE group compared with that in DICE group (86.5% vs. 87.5%, 58.3% vs. 63.2%, 42.9% vs.38.5%, respectively, P > 0.05). The major side effects were leucopenia, thrombocytopenia, and nausea in both groups. The bone marrow depression in DNCE group was significantly slighter than that in the DICE group (P < 0.05).</p><p><b>CONCLUSION</b>The efficacy of DNCE regimen is as good as DICE regimen, and the bone marrow toxicity is less severe in DNCE group than that in DICE regimen. Therefore, the DNCE regimen is an effective second-line salvage regimen for the treatment of refractory or relapsed aggressive and highly aggressive non-Hodgkin lymphoma.</p>

Pathogenesis,diagnosis and treatment of recurrent spontaneous abortion with immune type / 上海第二医科大学学报

Recurrent spontaneous abortion (RSA),which affects 1% to 5% of women of reproductive age,is difficult to treat in the clinical setting. In the investigations of immunopathogenesis,diagnosis and treatment of RSA since the late 1980s,it was found that RSA was associated with abnormal maternal local or systemic immune response,the pathogenesis of autoimmune RSA was mainly associated with antiphosphlipid antibody (APA),while that of alloimmune RSA was due to the disturbance of maternofetal immunological tolerance. Systemic etiological screening process and diagnosis systems of RSA with immune type were developed,and anticardiolipin (ACL)+? 2-GP1 combining multiple assay for effective diagnosis of RSA with immune type was initially established. According to dynamic monitoring clinical parameters before and during gestation,low-dose,short-course and individual immunosuppressive therapy and lymphocyte immunotherapy for RSA with immune type were initiated. The outcomes of the offsprings of patients with RSA were followed up,and the safety and validity of the therapies were confirmed. The research achievement leads to great progress in the diagnosis and treatment of RSA in China.

Study on the expression of transcription factor GATA-3 and T-bet mRNA in decidua of women with unexplained recurrent spontaneous abortion / 中华妇产科杂志

Objective To investigate the roles of transcription factor GATA-3 and T-bet at the fetal- maternal interface in the pathogenesis of unexplained recurrent spontaneous abortion(URSA).Methods The expression of GATA-3 and T-bet mRNA was examined by in situ hybridization.Decidua was obtained from 20 women with URSA and 20 normal pregnant(NP)women.Results(1)The number of GATA-3 positive cells per high power field in women with URSA(25?16)was significantly lower than those in NP women(38?16)(P