ABSTRACT
Objective:To investigate the clinicopathologic characteristics, gene mutation profile and prognostic influencing factors of diffuse large B-cell lymphoma (DLBCL) complicated with follicular lymphoma (FL) (DLBCL/FL).Methods:The clinicopathological data of 50 DLBCL/FL patients admitted to Rui Jin Hospital Affiliated of Shanghai Jiao Tong University School of Medicine from February 2018 to November 2021 were retrospectively analyzed. Targeted sequencing was performed to assess the mutation profile of 55 lymphoma-related genes. The clinicopathological characteristics were summarized to evaluate the short-term therapeutic efficacy of all patients. Kaplan-Meier method was used to analyze the overall survival (OS) and progression-free survival (PFS) of patients. Cox regression risk models were used to assess the factors affecting the OS and PFS.Results:Among 50 DLBCL/FL patients, 23 cases (46%) were male, 22 cases (44%) had an international prognosis index (IPI) score ≥ 2 points, 16 cases (32%) were double-expression lymphoma (DEL) and 4 cases (8%) were double-hit lymphoma (DHL). The complete response (CR) and overall response rates were 68% (34/50) and 78% (39/50), respectively after the first-line therapy. The median follow-up time was 23.3 months (5.1-50.9 months). The 2-year OS rate was 82.1% and 2-year PFS rate was 67.1%; and the median OS and PFS were not reached. Targeted sequencing results showed that the mutation frequencies of KMT2D, MYD88, TP53, BTG2, DTX1, EZH2, CD70, CREBBP, DUSP2, HIST1H1C, HIST1H1E and PRDM1 genes in this cohort were more than 15%. Multivariate Cox regression analysis showed that male ( HR = 4.264, 95% CI 1.144-15.896, P = 0.031) and IPI score ≥ 2 points ( HR = 6.800, 95% CI 1.771-37.741, P = 0.007) were independent risk factors of PFS in newly diagnosed DLBCL/FL patients, and TP53 mutation ( HR = 4.992, 95% CI 1.027-24.258, P = 0.046) was an risk influencing factor of OS. Conclusions:The proportion of male and female DLBCL/FL patients is similar, with a small proportion of DHL. Mutations of KMT2D, MYD88 and TP53 genes are commonly found in DLBCL/FL patients. Generally, DLBCL/FL patients can have a high overall response and good prognosis. Male and IPI score ≥ 2 points are the independent risk factors of PFS, and TP53 mutation is an independent risk factor of OS in DLBCL/FL patients.
ABSTRACT
The Ly-6 and uPAR (LU) domain-containing proteins represent a large family of cell-surface markers. In particular, mouse Ly-6A/Sca-1 is a widely used marker for various stem cells; however, its human ortholog is missing. In this study, based on a systematic survey and comparative genomic study of mouse and human LU domain-containing proteins, we identified a previously unannotated human gene encoding the candidate ortholog of mouse Ly-6A/Sca-1. This gene, hereby named LY6A, reversely overlaps with a lncRNA gene in the majority of exonic sequences. We found that LY6A is aberrantly expressed in pituitary tumors, but not in normal pituitary tissues, and may contribute to tumorigenesis. Similar to mouse Ly-6A/Sca-1, human LY6A is also upregulated by interferon, suggesting a conserved transcriptional regulatory mechanism between humans and mice. We cloned the full-length LY6A cDNA, whose encoded protein sequence, domain architecture, and exon-intron structures are all well conserved with mouse Ly-6A/Sca-1. Ectopic expression of the LY6A protein in cells demonstrates that it acts the same as mouse Ly-6A/Sca-1 in their processing and glycosylphosphatidylinositol anchoring to the cell membrane. Collectively, these studies unveil a novel human gene encoding a candidate biomarker and provide an interesting model gene for studying gene regulatory and evolutionary mechanisms.
Subject(s)
Humans , Membrane Proteins/genetics , Pituitary Neoplasms/genetics , BiomarkersABSTRACT
Objective:To investigate the clinicopathological characteristics, gene mutation profile, and prognostic factors of diffuse large B-cell lymphoma (DLBCL) in female genital tract.Methods:A retrospective analysis was performed on the clinicopathological data of 30 patients with female genital tract DLBCL who were admitted to Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from October 2003 to October 2021. Targeted sequencing was used to detect 55 lymphoma-related genes, and the gene mutation status of patients was evaluated. Kaplan-Meier method was used for survival analysis, and prognostic factors were analyzed by Cox proportional hazards model.Results:The median age of 30 female genital tract DLBCL patients at diagnosis was 58 years old (23-77 years old). The initial symptoms mainly included abdominal pain, distension, and masses (8 cases, 32%). Tumors most commonly located in the adnexal region (including ovaries and fallopian tubes) (13 cases, 45%), of which 9 cases were unilateral. Twenty-one cases (70%) had multiple extra-nodal involvements, 22 cases (73%) had Ann Arbor stage Ⅲ-Ⅳ, 8 cases (27%) had Eastern Cooperative Oncology Group (ECOG) score of ≥2, and 22 cases (73%) had elevated lactate dehydrogenase (LDH), 21 cases (70%) had International Prognostic Index (IPI) score of 3-5. Within 30 patients, 11 patients (37%) received surgery, and all patients received R-CHOP regimen-based chemotherapy. All 30 cases were evaluated for efficacy, the complete remission rate was 83% (25/30), the 5-year progression-free survival (PFS) rate was 69.7%, and the 5-year overall survival (OS) rate was 79.6%. Univariate analysis showed that ECOG score ≥2 was associated with worse OS ( P = 0.048). Among the 30 patients, 7 patients (23%) were primary and 23 patients (77%) were secondary. The proportions of patients with Ann Arbor stage Ⅲ-Ⅳ, IPI score 3-5 and elevated LDH in secondary patients were higher than those in primary patients (all P < 0.001), but there were no significant differences in PFS and OS between the two ( P values were 0.261 and 0.671). The targeted sequencing results of 16 patients showed that the mutation rates of PIM1, MYD88, KMT2D, TP53, CARD11, CCND3 and GNA13 were all > 20%, and TP53 mutation was associated with poorer PFS and OS ( P values 0.012 and 0.002). Conclusions:Female genital tract DLBCL is a rare invasive extranodal DLBCL with similar survival prognosis in primary and secondary patients. High-frequency mutations of PIM1, MYD88 and TP53 genes may provide new directions for treatment.
ABSTRACT
CD47 is widely expressed on the cell surface, and combines with signal regulatory protein α (SIRPα) to transmit the "don't eat me" signal, which plays a key role in self-recognition and tumor immune escape. Studies have shown that the high expression of CD47 in different hematologic neoplasms is associated with the occurrence, progression and poor prognosis of tumors. As a new immune checkpoint, CD47 is gradually becoming an effective target for tumor immunotherapy. and various related preclinical and clinical studies for hematologic neoplasms are underway. This article summarizes the application of CD47 in hematologic neoplasms, in order to provide references for the treatment.
ABSTRACT
The current standard of care in hematological malignancies has brought considerable clinical benefits to patients. However, important bottlenecks still limit optimal achievements following a current medical practice. The genetic complexity of the diseases and the heterogeneity of tumor clones cause difficulty in ensuring long-term efficacy of conventional treatments for most hematological disorders. Consequently, new treatment strategies are necessary to improve clinical outcomes. Chimeric antigen receptor T-cell (CAR T) immunotherapy opens a new path for targeted therapy of hematological malignancies. In this review, through a representative case study, we summarize the current experience of CAR T-cell therapy, the management of common side effects, the causative mechanisms of therapy resistance, and new strategies to improve the efficacy of CAR T-cell therapy.
Subject(s)
Humans , Hematologic Neoplasms/therapy , Immunotherapy/adverse effects , Neoplasms , Receptors, Chimeric Antigen , T-LymphocytesABSTRACT
Self-microemulsifying drug delivery systems (SMEDDSs) have recently returned to the limelight of academia and industry due to their enormous potential in oral delivery of biomacromolecules. However, information on gastrointestinal lipolysis and trans-epithelial transport of SMEDDS is rare. Aggregation-caused quenching (ACQ) fluorescent probes are utilized to visualize the
ABSTRACT
Objective:To assess the clinical value of metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid in pathogenic diagnosis of neurological infectious disease.Methods:Patients who were clinically diagnosed with infectious encephalitis and meningitis and treated in Department of Neurology, Affiliated Hospital of Chifeng University from March 2018 to September 2019 were retrospectively analyzed, including the clinical characteristics and data of mNGS and traditional laboratory test of pathogens.Results:Totally 104 patients with infectious encephalitis and meningitis were eligible for enrollment, and mNGS detected 22 bacterial species(22/104,21.15%), 24 viral species (24/104,23.08%), one fungal species (1/104,0.96%), one parasitic species (1/104,0.96%) and one mycoplasma species (1/104,0.96%).The three leading positive detections were varicella-zoster virus ( n=19), streptococcus ( n=7) and Mycobacterium tuberculosis ( n=4). Combined with traditional pathogen detection methods, clinical manifestations, final diagnosis and treatment results, the number of cases diagnosed by mNGS was 49 cases. The positive rate of the mNGS was 47.12% (49/104).False positives occurred in 21 (20.19%) patients. False negatives occurred in 34 (32.69%) patients. Conclusions:mNGS is more sensitive in evaluating the pathogens causing the infectious encephalitis and meningitis. It has advantages in accurate diagnosis of infectious encephalitis and meningitis.
ABSTRACT
Objective@#To observe whether the history of solid tumors affects the treatment response and survival situation of patients with diffuse large B-cell lymphoma (DLBCL) .@*Methods@#A retrospective study was conducted in 836 patients with DLBCL who were treated in the Department of Hematology at Ruijin Hospital from 2013 to 2018. Among them, 34 DLBCL patients who had the history of solid tumors were classified into double cancer group. From 802 patients without history of solid tumors, 68 DLBCL patients were selected as control group, using 1∶2 matching on propensity scores for age, gender, IPI score and etc. All patients included in the study had follow-up interviews through medical record and telephone for mortality from any cause. Treatment response and 3-year overall survival (OS) and progression-free survival (PFS) of two groups were analyzed.@*Results@#The complete remission rates after RCHOP (Rituximab+Cyclophosphamide+Vincristine+Adriamycin 50 mg/m2 or Epirubicin or Liposome Adriamycin+Prednisone) regimen were 79.4% and 67.6% in the double cancer group and the control group, respectively (P=0.210) . Among the 102 patients, 6 patients died in the double cancer group while 24 patients died in the control group and the median survival time of both two groups were not reached. The 3-year OS were (74.7±9.5) % and (63.5±6.1) % (χ2=2.791, P=0.095) , while 3-year PFS were (72.1±8.8) % and (54.3±6.4) % (χ2=1.400, P=0.237) in the double cancer group and the control group, respectively.@*Conclusion@#The history of solid tumors didn’t affect DLBCL patients’ treatment response and short-term survival.
ABSTRACT
Objective@#To compare clinical characteristics and prognosis between patients with primary (PTL) and secondary thyroid lymphoma (STL) .@*Methods@#A retrospective analysis was performed on 46 patients with thyroid lymphoma (PTL 19, STL 27) from January 2002 to October 2018.@*Results@#①PTL group included 4 males and 15 females, with a median age of 57 years. The STL group included 10 males and 17 females, with a median age of 61 years. Diffuse large B-cell lymphoma (DLBCL) was the main pathological subtype in both PTL and STL groups, with 14 cases (73.7%) and 20 cases (74.1%) respectively. In terms of clinical manifestations, goiter was the most common symptom in PTL patients 100.0% (19/19) , while 29.6% (8/27) STL had goiter (P<0.001) . The incidences of increased thyroglobulin antibody (TRAb) /thyroid peroxidase antibody (TPO) were 81.3% (13/16) in PTL group and 43.8% (7/16) in STL group (P=0.028) respectively. Concerning the clinical features of patients, only two PTL patients (10.5%) with advanced Ann Arbor stage (Ⅲ/Ⅳ) , while 21 (77.8%) STL experienced advanced Ann Arbor stage (P<0.001) . Elevated serum β2-MG were appeared in 1 (7.1%) PTL and 9 (47.4%) STL patients (P=0.013) , and advanced IPI score (3-5) was more common in STL than PTL (59.3% vs 5.3%, P<0.001) . ②Among the 17 PTL patients who received treatments, 15 (88.2%) achieved remission; as for STL patients received treatments, 23/25 (92.0%) were in remission. The 5-year overall survival (OS) rates of PTL (n=17) and STL groups (n=25) were (87.4±8.4) % and (70.0±13.1) % (P=0.433) respectively. ③The 5-year OS rate in 41 patients with B-cell thyroid lymphoma was (81.1±7.5) %. Univariate analysis showed that IPI score of 3-5 (P=0.040) and high level of serum IL-8 (P=0.022) were significantly associated with poor outcome.@*Conclusion@#DLBCL was the most common subtype in both PTL and STL, and goiter was the major symptom in PTL. IPI score of 3-5 and high level of serum IL-8 were unfavorable prognostic factors for patients with B-cell thyroid lymphoma.
ABSTRACT
Objective@#To evaluate the efficacy and safety of recombinant human thrombopoietin (rhTPO) treatment for primary immune thrombocytopenia (ITP) patients during the perioperative period.@*Methods@#Adult ITP patients who were refractory to first-line glucocorticoid therapy and underwent selective surgery were enrolled to be treated with rhTPO at the dosage of 1.5×104U/d subcutaneously during the perioperative period. rhTPO treatment would not be terminated until one of the following conditions occurred: ①Platelet counts met the requirement of surgery; ②Platelet counts were ≥100×109/L; ③Completed the 14 days of therapy. End points of the study were surgery rate, rhTPO therapy response rate, rescue therapy rate and adverse responses.@*Results@#42 patients were enrolled from Jan. 1, 2016 to Jun. 30, 2018. 14 were male and 28 were female. The median age was 60 (25-73) years old. There were no newly diagnosed patients. 5 patients were persistent and 37 were chronic. 27 patients completed selective surgery. The surgery rate was 64.3% (27/42) . Among them, 13 patients were under local anesthesia and 14 under general anesthesia. Of 42 cases receiving rhTPO therapy. 31 patients achieved responses, The overall response rate was of 73.8%. Among them, 24 patients achieved CR. The CR ratio was 77.4% (24/31) . 7 achieved response. The response ratio was 22.6% (7/31) . 11 patients did not respond to rhTPO therapy. The non-response rate was 26.2% (11/42) . The median time to reach CR was 7 (3-16) days. The median time to reach the peak of platelet counts were 10 (3-21) days. rhTPO was used for a median of 7 (3-14) days. The median platelet counts of patients undergoing surgery before rhTPO therapy, before surgery and at day 7 after surgery were 33 (20-89) ×109/L, 125 (78-245) ×109/L and 72 (30-250) ×109/L, respectively. The median peak of platelet counts was 149 (101-466) ×109/L. No infection, bleeding, thromboembolism and therapy-related adverse responses occurred in the patients.@*Conclusion@#rhTPO for ITP patients during the perioperative period is safe and effective.
ABSTRACT
Objective@#To identify the risk factors and clinical features associated with the interstitial pneumonia in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (RCHOP) or rituximab, cyclophosphamide, liposomal doxorubicin, vincristine and prednisone (RCDOP) regimens.@*Methods@#A retrospective study was conducted in 836 patients with DLBCL admitted to the Department of Hematology at Ruijin Hospital from 2013 to 2018. Among them, 114 patients were treated with RCDOP regimen. Using the method of propensity score matching according to age, gender, IPI score of patients, 114 patients treated with RCHOP regimen were selected as controls. Clinical data, including comorbidities, gender, age, B symptoms, international prognostic index (IPI) score, disease stage, serum lactic dehydrogenase (LDH) and β2 microglobulin (β2-MG) level were collected and the risk factors of interstitial pneumonia were further analyzed.@*Results@#The interstitial pneumonia developed more frequently in RCDOP group than RCHOP group (28.95% vs 2.60%, P<0.01) . As the dose of liposomal doxorubicin elevated from 25-30 mg/m2 to 35-40 mg/m2, the incidence of interstitial pneumonia accordingly increased from 17.30% to 38.71% (P<0.05) . By multivariate analysis, disease stage was an independent factor of interstitial pneumonitis.@*Conclusions@#Front line regimens containing liposomal doxorubicin in DLBCL patients link to a higher incidence of dose-dependent interstitial pneumonia. Prevention and surveillance should be emphasized in future studies.
ABSTRACT
Objective@#To explore the clinical characteristics of follicular lymphoma (FL) in the era of rituximab combined with chemotherapy and the prognostic significance of the follicular lymphoma international prognostic index (FLIPI), follicular lymphoma international prognostic index 2 (FLIPI2), international prognostic index (IPI), revised international prognostic index (R-IPI), National Comprehensive Cancer Network international prognostic index (NCCN-IPI) among Chinese patients.@*Methods@#229 FL patients who were treated initially with rituximab combined with CHOP-like (cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy from November 2008 to April 2018 were analyzed retrospectively and all were scored by the above clinical index. Univariate and multivariate survival analysis were performed on 201 patients who completed the treatment and were followed regularly.@*Results@#In the univariate survival analysis, age>60 years, hemoglobin<120 g/L, elevated serumβ2- macroglobulin, involvement of bone marrow and elevated CRP were the risk prognostic factors for overall survival (OS) and progression free survival (PFS). Moreover, the analysis of the OS and PFS between rituximab (R) maintenance (RM) group and non-maintenance (non-RM) group showed that the OS and PFS of RM group were better than those of non-RM. In the multivariate analysis of OS, hemoglobin<120 g/L, involvement of bone marrow, elevated CRP and non-RM were independent prognostic factors. In the multivariate analysis of PFS, hemoglobin<120 g/L, CRP and non-RM were independent prognostic factors. When FLIPI2 was included in the multivariate analysis, CRP and FLIPI2 were independent prognostic factors in both OS and PFS, and non-RM was independent prognostic factors in PFS.@*Conclusion@#FLIPI2 is the better risk stratification in FL patients in the era of rituximab.
ABSTRACT
Autoimmune diseases (ADs) increase the risk of non-Hodgkin's lymphoma and contribute to poor prognosis of patients. However, the association between immunologic markers and clinical outcome has rarely been investigated. This study aims to analyze the prognostic value of pretreatment immunologic markers in newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL). We retrospectively reviewed the data on 502 patients with DLBCL treated in our institution from January 2013 to March 2018. Survival functions were estimated using Kaplan-Meier method and Cox regression model. The 3-year progression free survival (PFS) and overall survival (OS) rates were 70.2% and 80.9%, respectively, and the complete remission (CR) rate was 78.1%. Among the patients, those with multiple ( ⩾ 3) abnormal immunologic markers had significantly shorter 3-year PFS (52.7% vs. 77.3%, P 60 years for OS (P = 0.014). In conclusion, the immunologic status was closely related to lymphoma progression, and this study provides new insights into the risk stratification of patients with DLBCL.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Antineoplastic Combined Chemotherapy Protocols , Therapeutic Uses , Biomarkers , China , Disease Progression , Immunotherapy , Methods , Lymphoma, Large B-Cell, Diffuse , Mortality , Therapeutics , Multivariate Analysis , Prognosis , Retrospective Studies , Survival Analysis , Survival RateABSTRACT
Objective@#To evaluate the clinical and prognostic significance of hepatitis B virus infection on patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL).@*Methods@#A retrospective analysis was performed in 81 relapsed/refractory DLBCL cases who were treated with salvage regimens from January 2004 to November 2016. The patients were divided into two group, HBsAg positive and HBsAg negative group, and assessed the clinical features and survival time of two groups.@*Results@#Twenty-four (29.6%) patients were HBsAg positive and 57(70.4%) were negative. HBsAg-positive DLBCL patients showed unique clinical features, including more younger patients (P=0.005), more advanced Ann Arbor stage (P<0.001), high-risk IPI (P=0.010), more hypohemoglobin (P=0.015), especially extra-nodal involvement (P=0.038) and recurrence (P=0.002). Overall response rate (29.2% vs 68.4%, χ2=10.720, P=0.001) and median overall survival time [(11.3±2.9) months vs (30.0±7.6) months, χ2=28.175, P<0.001] were inferior in HBsAg-positive patients, respectively.@*Conclusion@#To strictly control HBV infection plays an important role on the survival and prognosis of relapsed/refractory lymphoma patients.
ABSTRACT
Objective@#To investigate the efficacy of RCDOP (Rituximab, cyclophosphamide, liposome doxorubicin, vincristine and prednisone) regimen in patients with de novo diffuse large B-cell lymphoma (DLBCL), especially in those patients with multiple extra-nodal involvement or Bulky diseases. @*Methods@#A total of 87 newly diagnosed DLBCL patients who received RCDOP regimen from October 2012 to October 2017 were enrolled into this study. Survival functions were estimated using the Kaplan-Meier method and compared by the log-rank test, and χ2 tests were used for categorical data. @*Results@#Among the 87 DLBCL patients treated with RCDOP regimen, 81 patients achieved complete remission (CR) or partial remission (PR), with ORR as 93.1%. Patients were further classified into groups, according to the risk factors, such as IPI scores, multiple extra-nodal involvement, bulky disease, age>60, tumor Ki-67>80%, elevated serum LDH level and advanced Ann Arbor stage. The progression-free survival (PFS, P=0.084) and overall survival (OS, P=0.515) had no statistical difference among the IPI low risk (0-1 score) group, intermediate risk (2-3 scores) group and high risk (4-5 scores) group. Similarly, no statistical difference were fou nd in PFS and OS of patients with extra-nodal involvements ≥2 (P=0.303 and P=0.624), with bulky disease (P=0.518 and P=0.466), with age>60 (P=0.600 and P=0.183), with elevated serum LDH level (P=0.054 and P=0.880), with advanced Ann Arbor stage (P=0.075 and P=0.286), and with tumor Ki-67 over 80% (P=0.190 and P=0.109), when compared with those of patients without these risk factors. @*Conclusion@#RCDOP can improve the therapeutic effect and prognosis of DLBCL patients with certain high risk factors, such as intermediate and high IPI risks, multiple extra-nodal involvements, bulky disease, age over 60, elevated LDH level, advanced Ann Arbor stage and tumor Ki-67 over 80%.
ABSTRACT
Objective@#To explore the clinical features, laboratory examinations and diagnosis progress of primary pleural diffuse large B-cell lymphoma (DLBCL) and analyze the relationship between immune thrombocytopenia (ITP) and lymphoma, and to improve the diagnostic level of the rare disease.@*Methods@#The clinical features, diagnosis and treatment of one primary pleural DLBCL patient with ITP in Ruijin Hospital of Shanghai Jiao Tong University School of Medicine were observed. The related literatures were also reviewed.@*Results@#The patient was admitted to the hospital due to repeated chest tightness and shortness of breath for 6 months. Ultrasonic examination, chest CT scan, PET-CT and pleural effusion puncture were performed. The main clinical feature was only pleural effusion without hepatosplenomegaly, enlargement of lymph nodes and any other lesions. Pathological study of pleural effusion confirmed the diagnosis of DLBCL. The patient was suffered from ITP for 30 years. After confirmed diagnosis, 6 courses of R-CHOP regimen had been performed. Mid-term assessment showed the complete absorption of pleural effusion and achieved complete remission.@*Conclusions@#Primary pleural DLBCL is a rare disease. It is easy to misdiagnose due to the lack of specificity in clinical and imaging manifestations. The final diagnosis ultimately depends on histopathology. ITP can occur prior to lymphoma or onset of lymphoma, and a few patients can present with ITP in the course of lymphoma.
ABSTRACT
Biomimetic nanocarriers are emerging as efficient vehicles to facilitate dietary absorption of biomacromolecules. In this study, two vitamins, thiamine and niacin, are employed to decorate liposomes loaded with insulin, thus facilitating oral absorption vitamin ligand-receptor interactions. Both vitamins are conjugated with stearamine, which works to anchor the ligands to the surface of liposomes. Liposomes prepared under optimum conditions have a mean particle size of 125-150 nm and an insulin entrapment efficiency of approximately 30%-36%. Encapsulation into liposomes helps to stabilize insulin due to improved resistance against enzymatic disruption, with 60% and 80% of the insulin left after 4 h when incubated in simulated gastric and intestinal fluids, respectively, whereas non-encapsulated insulin is broken down completely at 0.5 h. Preservation of insulin bioactivity against preparative stresses is validated by intra-peritoneal injection of insulin after release from various liposomes using the surfactant Triton X-100. In a diabetic rat model chemically induced by streptozotocin, both thiamine- and niacin-decorated liposomes showed a comparable and sustained mild hypoglycemic effect. The superiority of decorated liposomes over conventional liposomes highlights the contribution of vitamin ligands. It is concluded that decoration of liposomes with thiamine or niacin facilitates interactions with gastrointestinal vitamin receptors and thereby facilitates oral absorption of insulin-loaded liposomes.
ABSTRACT
Objective To prepare methoxy polyethylene glycol (mPEG)-polycaprolactone (PCL) nanoparticles loading a water-quenching fluorescent probe and to evaluate its in vitro characteristics and stability.Methods PCL nanoparticles and mPEG-PCL nanoparticles with different mPEG chain lengths (mPEG5k,mPEG2k) loading the waterquenching fluorescent probe P2 were prepared by an emulsification/solvent evaporation method using PCL and mPEG-PCL as materials.In vitro characteristics such as morphology,particle size and distribution were evaluated.The P2 probe displayed fluorescent signals when encapsulated in the matrix of the nanoparticles,but quenched immediately when released into water.Based on this properties of P2 probe,the stability of various nanoparticles in different aqueous media was investigated.Results The prepared mPEG-PCL nanoparticles showed a particle size of about 200 nm,narrow size distribution,polydispersity index below 0.06 and near neutral surface potentials with spherical morphology and smooth surfaces.In buffers of different pHs and simulated bio-relevant media,all nanoparticles showed very good stability without significant change in particle size,polydispersity index and fluorescence intensity.Conclusion mPEG-PCL nanoparticles have promising in vitro characteristics and robust stability.It is fast and convenient to monitor the stability of nanoparticles by using the water-quenching probe.
ABSTRACT
Objective · To evaluate the efficacy and prognostic factors of ifosfamide-cisplatin-etoposide (ICE) chemotherapy as salvage regimen for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL).Methods · A retrospective analysis was performed on 84 relapsed/refractory DLBCL patients who were treated with ICE salvage regimen at Ruijin Hospital (Shanghai Jiao Tong University School of Medicine,China) from July 2004 to June 2016.Overall survival (OS) was analyzed by Kaplan-Meier method and multivariate Cox proportional hazards models.Results· Of the 84 patients who were treated with ICE regimen,37 (44.0％) patients had responses,including 26 (31.0％) achieving complete remission.The median number of cycles per patient was 3 (range 1-6 cycles).The 1-year and 2-year OS rates were 49.5％ and 30.0％,respectively.The median OS time was 12.2 months.On univariate analysis,patients with early progression/recurrence (P=0.041) and a high-intermediate/high risk according to the international prognostic index (IPI) (P=0.024) and NCCN-IPI (P=0.002) had poorer outcomes.While improved outcome was found in patients in complete remission after chemotherapy (P=0.000).The multivariate analysis revealed that the intermediate-high/high risk according to NCCN-IPI was an independent risk factor,and remission after chemotherapy was an independent prognostic factor for prolonging survival.Conclusion· The ICE regimen can be used as an effective salvage therapy for patients with relapsed/refractory DLBCL.
ABSTRACT
Objective@#To validate the prognostic value of NCCN-International Prognostic Index (NCCN-IPI) for patients with peripheral T-cell lymphoma (PTCL) treated with CHOP-based chemotherapy.@*Methods@#A retrospective analysis in 162 PTCL patients who were initially diagnosed and treated in Rui Jin Hospital from January 2003 to May 2013 was conducted. Baseline characteristics were collected, and survival analysis was performed according to the IPI and NCCN-IPI model.@*Results@#The estimated 5-year overall survival (OS) rate and progression free survival (PFS) rate were 33% and 20%, with median OS and PFS of 17.0 months and 9.2 months, respectively. Multivariate analysis indicated ECOG score (PFS: HR=2.418, 95%CI 1.535-3.809, P<0.001; OS: HR=2.347, 95%CI 1.435-3.839, P= 0.001) , specific extra-nodal sites (PFS: HR=1.800, 95%CI 1.216-2.665, P=0.003; OS: HR=1.608, 95% CI 1.054-2.454, P=0.027) and pathology type (PFS: HR=0.424, 95% CI 0.184-0.975, P=0.043; OS: HR=0.276, 95% CI 0.087-0.877, P=0.029) were independent prognostic factors of OS and PFS for the patients with PTCL. The survival rates of low risk patients based on NCCI-IPI were remarkably higher than the counterparts based on IPI (5-year OS 74% vs 54%, χ2=5.041, P=0.025, 5-year PFS 50% vs 38%, χ2= 5.295, P=0.021) . NCCN-IPI was outstanding to identify the subgroup of low risk patients with PTCL, who may benefit from conventional chemotherapy such as CHOP or CHOP-like regimen.@*Conclusion@#NCCN-IPI is more powerful for low risk PTCL patients and a strong supplement for IPI.