Search

Conjugated microporous polymers (CMPs) have great potential in the field of CO2 adsorption due to their high specific surface area and molecular structure designability, and the introduction of polar heteroatoms can further improve their CO2 adsorption performance. Boronic acid-based conjugated microporous polymers (BACMPs) rich of N and B heteroatom were obtained by Buchwald-Hartwig coupling reaction with tris(4-aminophenyl)amine (TA) and 3,5-dibromophenylboronic acid (BA). The pore size of BACMPs can be controlled by changing the monomer reaction ratio. The structure and morphology of BACMPs were characterized by Fourier transform infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy and N2 adsorption and desorption tests, and the CO2 adsorption and desorption tests of BACMPs were carried out to explore their CO2 adsorption properties. The results show that the obtained BACMPs have a large number of micropores, the Brunauer-Emmett-Teller specific surface area can reach up to 475 m²/g, and the CO2 adsorption mass fraction can reach up to 8.53% at 100 kPa and 273 K, which has the application prospect of CO2 adsorption. [ABSTRACT FROM AUTHOR]

A rapid method for the determination of free acids in chloropalladium acid solution was developed by using an automatic potentiometric titration and composite glass electrode. The results show that the automatic potentiometric titration can accurately distinguish the end points of the reaction of free acid with sodium hydroxide and chloropalladium acid with sodium hydroxide, the maximum jump point of the first step EP1 is the target end point. The recovery of hydrochloric acid is between 85% and 110%, and the relative standard deviation (RSD) is less than 2%. The method is intuitionistic, rapid and accurate. It is suitable for the determination of free acid in chloropalladium acid solution. [ABSTRACT FROM AUTHOR]

Objective To analyze the clinical characteristics and prognosis of newly diagnosed multiple myeloma (MM) patients with different types of extramedullary disease (EMD). Methods Data of gender, age, immunoglobulin type, DS stage, ISS stage and other clinical characteristics of 99 MM patients with EMD who were admitted to our hospital and had complete clinical data were retrospectively analyzed. The survival analysis and prognostic analysis on patients with different types of extramedullary diseases were performed, and the prognostic significance of different therapeutic regimens was explored. Results There were no significant differences in clinical characteristics between MM patients with the bonerelated EMD (bEMD, n=57) and strict EMD (sEMD, n=42, P＞0.05). The two types of extramedullary diseases were mainly found in ribs (42.1%) and soft tissues (50.0%) respectively. There were significant differences in median OS time (45 months vs. 15 months, P＜0.05) and median PFS (20 months vs. 10 months, P＜0.05) between bEMD group and sEMD group. It was found that age≥60 years (HR=2.333, 95%CI:1.025-5.309, P＜0.05),β2-MG≥2.7 mg/L (HR=4.361, 95%CI:1.304-14.587, P＜0.05) and mutation of TP53 (HR=3.697, 95%CI:1.015-13.469,P＜0.05) were independent prognostic factors affecting OS in EMD patients. The median PFS (49 months vs. 9 months, P＜0.05) and median OS (79 months vs. 12 months, P＜0.05) of patients with sequential ASCT after bortezomi-induced chemotherapy in the sEMD group were statistically significant compared with those without ASCT. Conclusion The prognosis of MM patients with sEMD is worse than that of bEMD patients. The sequential autologous hematopoietic stem cell transplantation with bortezomib chemotherapy may prolong the survival and improve prognosis of patients with sEMD. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Dalian University of Technology / Dalian Ligong Daxue Xuebao is the property of Journal of Dalian University of Technology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

2-chloro-5-trifluoromethyl pyridine-4-yl-boronic acid was prepared with 2-chloro-4-iodo-5-trifluoromethyl pyridine as the raw material through reaction with n- butyl lithium reagent. Several reaction conditions of the synthesis process were studied through the experiment. The purity and structure of the products were characterized by HPLC, FTIR and ¹H NMR. Experimental result shows that when the temperature is -70 °C, the reaction time is 2 h, the molar ratio of n(C6 H2ClF3IN) : n(C12H27BO3) : n(C4H9Li) is=l.00 : 1.20 : 1.20, and the pH is 9.0, the yield of 2-chloro-5-trifluoromethyl pyridine-4-yl-boronic acid reaches 83.10%, and its purity is up to 98.65%. [ABSTRACT FROM AUTHOR]

Phosphorylation and glycosylation of proteins, two of the most widely studied post-translational modifications (PTMs), have shown increasing potential in the early non-invasive diagnosis, prognosis, and therapeutic evaluation of diseases. Besides regulating the function of cell membranes and intracellular signal transduction, protein phosphorylation participates in mitochondrial function and cellular and transcriptional metabolism. Protein glycosylation plays an important role in both intracellular and extracellular signal transduction and intracellular endocytosis. Aberrant phosphorylation and glycosylation of proteins are frequently observed in clinical proteomic studies and in the discovery of disease-related biomarkers. There are generally three methods for detecting protein phosphorylation/glycosylation: isotope radiolabeling, western blotting, and mass spectrometry. Mass spectrometry has become the most important and advantageous detection method due to its high throughput and time- and labor-efficiency. However, phosphopeptides and glycopeptides have low stoichiometry and ionization efficiency, and a large number of non-phosphopeptides and -glycopeptides interference. These issues make it difficult to directly detect phosphopeptides and glycopeptides by mass spectrometry. Therefore, the enrichment of phosphopeptides and glycopeptides before mass spectrometry detection is a key step. At present, a variety of materials have been developed for enrichment studies of phosphopeptides and glycopeptides. For example, immobilized metal affinity (IMAC) and metal oxide affinity chromatography (MOAC) methods are mostly used for the enrichment of phosphopeptides. The IMAC mainly uses positively charged metal ions and negatively charged phosphate groups to attract each other for the purpose of enriching phosphopeptides. MOAC materials rely on the chelation of metal atoms and phosphate oxygens to capture phosphopeptides. IMAC and MOAC materials rely on strong interactions between metals and phosphate groups, which often lead to difficult elution. The enrichment method for glycopeptides is mainly based on the difference in hydrophilicity between glycopeptides and non-glycopeptides, which are mainly enriched by hydrophilic interaction chromatography (HILIC). In addition, materials containing compounds such as boronic acid and lectin materials are also widely used for the separation and enrichment of glycopeptides. Smart responsive materials have also been successively reported for the enrichment of phosphopeptides and glycopeptides due to their unique responsiveness and reversibility. Smart responsive materials can respond to external stimuli; undergo structural and property changes; and convert signals such as optical, electrical, thermal, and mechanical into biochemical signals. Responsive molecules are a prerequisite for determining the response properties of smart responsive materials, and their reversible isomerization under different stimuli (such as temperature, pH, light, mechanical stress, and electromagnetic field) will lead to dynamic changes in the physical and chemical properties of materials. Compared with traditional materials, smart responsive materials can be reversibly "turned on" and "off" with better controllability. Exogenous stimuli, including temperature, light, ultrasound, electromagnetic field, and mechanical stress, can be implemented in a specific time and space. Exogenous responsive materials do not depend on changes in the reaction system itself and are non-invasive. Enzymes, pH, redox, solution polarity, and ionic strength are endogenous stimuli. Endogenous responsive materials depend on changes in the reaction system itself, and sometimes the regulation process requires the introduction of other chemicals into the reaction system. The identification, capture, and release of phosphopeptides or glycopeptides can be achieved by modulating the interactions between smart responsive materials and phosphopeptides or glycopeptides (such as hydrogen bonds, and electrostatic and hydrophobic interactions). This review classifies smart responsive materials according to the types of stimuli, which are specifically divided into exogenous and endogenous responsive materials. The enrichment of phosphopeptides and glycopeptides of exogenous/endogenous responsive materials and endogenous/exogenous co-responsive materials are summarized. In addition, we discuss the development prospects of smart responsive materials in the enrichment of phosphopeptides and glycopeptides, and also raised the challenges existing in the application of smart responsive materials in other protein post-translational modifications.

Objective: To explore and analyze the risk factors of herpes zoster in patients with multiple myeloma (MM) during the chemotherapy with bortezomib., Methods: Clinical data of 85 MM patients treated with bontizomib from January 2015 to January 2019 were selected and divided into case group and control group accroding to the occurred of herpes zoster. The clinical characteristic, treatment outcome and related factor of herpes zoster were retrospective analyzed., Results: Twenty of the 85 patients with MM treated with bortezomib developed herpes zoster occurred (23.5%). Single-factor analysis showed that age≥65 years, lymphocytopenia occurred before treatment, neutropenia occurred before treatment, ECOG score≥2, application of cyclophosphamide, absence of preventive antiviral therapy were associated with the genesis of herpes zoster (P＜0.05). Multivariate logistic regression analysis showed that lymphocytopenia occurred before treatment, the application of cyclophosphamide and the absence of preventive antiviral therapy were the independent risk factors for herpes zoster (P＜0.05)., Conclusion: The incidence of herpes zoster is high in the multiple myeloma patients treated with bortezomib. Lymphocytopenia occurred before treatment, the application of cyclophosphamide, and the absence of prophylactic antiviral therapy are the important risk factors for herpes zoster, for which the clinicians should attach great importance.

Protein N -glycosylation plays a crucial role in the folding, transportation, and localization of proteins, and participates in many important biological processes such as receptor activation and signal transduction. An increasing number of studies have shown that abnormal protein glycosylation is closely related to various diseases. Therefore, N -glycosylated proteins are potential candidates for become new biomarkers or drug targets. The current research strategy for N -glycosylated proteins is to first digest the protease into peptides and then identify them by mass spectrometry. In sample preparation processing, enrichment and separation of N -glycopeptides have become the vital step for glycoproteomic analysis. However, because of their low abundance and poor ionization, mass spectrometric identification of N -glycopeptides in complex samples remains a challenging task. Therefore, the development of a selective enrichment strategy for N -glycopeptides from complex biological samples is necessary. In this work, new functional nanomaterials were prepared through a simple, convenient, and efficient two-step "Au-S" reaction. In short, the "Au-S" bond was first used to load nano-gold wires on the surface of molybdenum disulfide (MoS 2 ), and then to connect these wires to 4-mercaptophenylboronic acid (4-MPB). The resulting nanomaterial named MoS 2 /Au/4-MPB was successfully prepared by serial functionalization of ultra-thin two-dimensional MoS 2 , nano-gold wires and 4-MPB for the efficient enrichment of N -glycopeptides. The layered structure of molybdenum disulfide nanomaterials can provide numerous modifiable sites for the reaction, allowing for convenient modification of the nano-gold wires. The functional group 4-MPB has high affinity for N -glycopeptides, and it can selectively enrich them in biological samples. In order to evaluate the N -glycopeptide enrichment performance of MoS 2 /Au/4-MPB, standard proteins human immunoglobulin G (IgG) and bovine serum albumin (BSA) trypsin digests were used. Thus, facilitated interactions with N -glycopeptides for boric acid-based retention could be expected. Low femtomolar detection sensitivity, 1:1000 enrichment selectivity, and 100 μg/mg loading capacity were achieved for N -glycopeptide enrichment. In the application of this material to biological samples, exosomes were chosen as the research objects. On the one hand, exosomes serve as a new class of carriers for intercellular communication and drug delivery. Almost all types of cells can secrete exosomes. On the other hand, urine is another potential source for liquid biopsy samples in addition to blood. Obtaining urine samples is a less invasive process, and urine samples are easier to handle and save as compared to blood samples. Exosomes can also be detected in urine. Cell-specific components such as proteins, lipids, and nucleic acids can provide diverse information, which is of great significance in disease diagnosis and treatment. However, there are only a few studies on urinary exosomes N -glycoprotein group. In this research, N -glycoproteins were successfully identified in urine exosomes. In three replicate experiments, 536, 515 and 487 N -glycosylated peptides were identified from 279, 270 and 279 N -glycoproteins, respectively. After de-duplication of the three sets of data, a total of 768 N -glycopeptides corresponding to 377 N -glycoproteins were identified. This result indicates that the novel nanocomposite has good enrichment selectivity and sensitivity for N -glycopeptides enrichment in complex biological samples, and this method provides a new method for glycoproteomics research.

Objective: To evaluate the therapeutic effect and adverse reactions of the maintenance therapies with Thalidomine or Bortezomib in the patients with newly diagnosed multiple myeloma (MM), so as to provide a reference for clinical treatment., Methods: A retrospective analysis was conducted to compare the progression-free survival (PFS), overall survival (OS) and adverse reaction rate of 23 MM patients received the maintenance therapies of Bortezomib and of 68 MM patients received maintenance therapy of Thalidomine., Results: The maintenance therapy with Bortezomib could extend the PFS of MM patients as compared with Thalidomine (PFS rate of patients on the maintenance therapy of Bortezomib in 12th, and 24th month was 100%, 88.89%, and that of Thalidomine-treated group was 72.31%, 47.54%). What's more, some specific patients could get better 2-year PFS rate in Bortezomib group than that in Thalidomine group, such as older than 65 years old, after autologous hematopoietic stem cell transplantation(ASCT), having genetic changes, extramedullary lesions, poor renal function, low serum free light chain ratio, high β2-MG, anemia, high LDH, VGPR of induction and consolidation therapy. The OS rate of Bortezomib on 18th, 24th and 30th month was 100%, 88.89%, 80% verus 91.52%,83.63%,72.90% of the group with thalidemide at the same time. As for 2-year OS rate, the Bortezomib group was higher than Thalidomine without statistical differences. However, the patients such as older than 65 years old, poor renal function and with extramedullary lesions, would also get higher 2-year OS rate from Bortezomi. Bortezomib and thalidomide could cause bone marrow suppression, peripheral neuritis and other adverse reactions., Conclusion: The efficacy of maintenance therapy with Bortezomib is superior to thalidomide. As a conclusion, bortezomib is a better option for maintenance therapy of MM patient.

Objective: To investigate if NS-398 could enhance the chemosensitivity of Bortezomib (BOR) on human multiple myeloma RPMI 8226 cells., Methods: After the treatment of NS-398 combined with BOR, MTT assay was used to detect the proliferation inhibition effect on human multiply myeloma RPMI 8226 cells in vitro, Flow cytometry was used to analyze their effect of apoptosis and cell cycle; the caspase-3 activity of different treatment group was detected by using ELISA and the activity of Cox-2 was measured by using Cox-2 activity assay kit., Results: The inhibitory rate of NS-398 combined with BOR was higher than that of NS-398 or BOR alone(Q>0.85). After treatment of NS-398 combined with BOR, the percentage of cells arrested in the G 0 /G 1 phase and apoptotic rate were both higher than that of treatment with each drug alone(Q>1.15). The caspase-3 activity in cells treated with combined of NS-398 and BOR was significantly higher than that of treatment of each drug alone(Q>1.15)., Conclusion: NS-398 combined with BOR shows a synergistic effect on the growth inhibition of RPMI 8226 cells in vitro.

Objective: To observe the efficacy of chemotherapy consisted of bortezomib as main druy in maintenance therapy for recurrence of newly diagnosed MM patients., Methods: The clinical data and outcome of 37 MM patients during 2008-2013 were analyzed retrospectively, the 37 MM patients were divided into 2 group: 19 cases including 13 cases of newly diagnosed MM with symptoms and 6 cases of relapsed refractory MM were enrolled in group A; 17 cases of newly diagnosed MM with symptoms were enrolled in group B. The patients of group A received maintenance therapy consisted of bortezomib plus dexamethasone (VD group), while the patient group B received maintenance therapy consisted of melphalan plus prednisone(MP group), then the therapeutic efficacy of 2 group was compared., Results: The overall response rate(ORR) in VD groupe was 84.2%(16/19), out of which CR rate reached 42%(8/19), PR rate reached 31.6%(6/19), MR rate reached 10.5%(3/19). During median follow-up for 21.8(5-51) months, death occurred, while the ORR in MP group was 52(9/17), out of which CR rate was 23.5%(4/17), PR rate reached 23.5%(4/17), MR rate reached 5.9%(1/17). Druing median follow-up for 16.4(4-39) months, the worteity reaced 64.7%(11/17). The differencr between 2 groups was significant(P<0.05). The median OS time of patients in VD group was 21.6 months, that in MP group was 17.9 months(P<0.05). The median PFS in VD group and MP group were 13.4 and 9.4 months respectively(P<0.001)., Conclusion: The ORR and CR rates of bortezomib maintenance therapy for newly diagnosed and relapsed / refractory MM patients are very high, and its toxicity can be controlled, therefore, the patients need maintenance therapy after remission.

Objective: To observe the efficacy and safety of CTD (cyclophosphamide, thalidomide, dexamethasone) and PCD (bortezomib, cyclophosphamide, dexamethasone) regimens in treatment of patients with newly diagnosed multiple myeloma (NDMM) . Methods: A retrospective analysis was carried out on 88 cases of NDMM patients admitted to our hospital from July 2013 to January 2016, including 49 cases in CTD group and 39 cases in PCD group. The outcomes of two different regimens were analyzed, including response, prognosis, and adverse events. Results: The total overall remission rates (ORR, better than PR) of CTD and PCD were 65.3% (32/49) and 84.6% (33/39) , while very good partial response (VGPR) were 30.6% (15/49) and 53.8% (21/39) , and differences were statistically significant ( P =0.041, P =0.028) . The median follow-up was 11.5 (3-33) months. The median progression-free survival (PFS) was (23.0±4.5) months in CTD groups, but it was not achieved in PCD group, with statistically significant differences ( P =0.050) . Medial overall survival was not achieved in both two groups, without statistically significant difference ( P =0.257) . There were statistical differences between patients with minor response (MR) and patients without MR in medium OS in CTD group ( P =0.005) , and there were statistical difference between patients with VGPR and without VGPR in medium OS in CTD group ( P =0.042) . Infection was a common adverse event in two groups. The incidences of peripheral neuropathy and herpes zoster were markedly higher in PCD group than CTD group, and the incidences of thrombus, palpation and rash, etc., were higher in CTD group. Conclusion: Both CTD and PCD regimens were effective first-line induction chemotherapy choice for NDMM. PCD regimen is better than CTD in treatment power and deep remission.

Objective: To evaluate the efficacy and safety of high-dose intravenous mecobalamin (HDIME) for the treatment of bortezomib-induced peripheral neuropathy(BIPN) in the patients with multiple myeloma (MM)., Methods: A total of 65 newly diagonsed patients with multiple myeloma receiving bortezomib in Tianjin Medical University General Hospital were enrolled in this single-centre randomized clinical trial from July 2012 to May 2016. Out of 65 patients 38 in control group received bortezomib-based chemotherapy and 27 patients in HDIME group received the additional high-dose intravenous mecobalamin., Results: The incidence of BIPN in HDIME group was lower than that in control group(29.63% vs 55.26%, χ 2 =4.197,P<0.05). Whether the BIPN rate of Grade 2 or 3 and above in HDIME group significantly decreased as compared with control group(18.52% vs 47.37%,χ 2 =5.746,P<0.05) (3.71% vs 21.05%, χ 2 =3.983,P<0.05). The BIPN rate of less than 5 cycles of bortezomib was not significantly different between HDIME and control groups(χ 2 =2.714,P>0.05). Overall effective rate of HDIME group and control group was 77.78% and 73.68%(P>0.05) respectively. Neither PFS nor OS was significantly different between HDIME group and control group(P>0.05). Treatment-related toxicity was only mild rash in 1 case. No other side-effects including nausea, abdominal pain, and hypotension occurred., Conclusion: HDIME has a good efficacy for the prophylaxis BIPN and and without serious side effects.

Objective: To investigate the effects of berberine in combination with bortezomib on proliferation and apoptosis of multiple myeloma (MM) cell line. Methods: MM cell line U266 cells were treated with berberine and/or bortezomib. The effects of berberine and/or bortezomib on proliferation of cells were measured by methylthiazolyl tetrazolium bromide (MTT). Flow cytometric Annexin Ⅴ/PI double staining method was used to detect effect of either drug alone or in combination on apoptosis of MM cell line U266. ELISA was used to measure the expression of casepase-3,-8,-9 affected by the two drugs. Western blot was used to detect the expression of the apoptosis-related protein TRADD and FADD. King formula was used to determine if there was a synergistic effect of berberine in combination with bortezomib. Results: ① Both berberine and bortezomib as single agent had dose- and time-dependent effects of proliferation inhibition on U266 cells. Berberine (20 μmol/L) and bortezomib (5 nmol/L) had a synergistic effect of proliferation inhibition (Q value: 1.31-1.65). ② The proportion of early stage apoptosis in both single agent groups and combination group significantly increased compared to control group ( P < 0.05). Berberine and bortezomib had a synergistic effect on cell apoptosis (Q value after 6 h and 12 h were 0.896 and 1.197, respectively). ③ Berberine in combination with bortezomib significantly upregulated expressions of caspase-3, -8 and -9, which were statistically significant ( P <0.05). ④Berberine in combination with bortezomib significantly upregulated expressions of TRADD (0.91±0.01, 0.70±0.01) and FADD (0.98±0.01, 0.98±0.01) compared with control group (both P <0.05). Conclusion: Berberine in combination with bortezomib had synergistic effects on proliferation inhibition and apoptosis, which were mediated by up-regulated levels of TRADD and FADD.

Objective: To investigate the efficacy and outcome in newly diagnosed multiple myeloma (MM) patients with renal insufficiency using bortezomib- or thalidomide-based regimens as front line treatment. Method: Sixty-nine newly diagnosed MM patients with renal insufficiency were retrospectively analyzed from August 2006 to August 2014. Results: ① Among thirty-nine patients with bortezomib based regimens (the bortezomib group), the overall response rate (ORR) was 89.7% and complete response (CR) plus near CR(nCR) rate was 41.0%. By contrast, among thirty patients with thalidomide based regimens (the thalidomide group), the ORR was 83.3% and CR+ nCR rate was 26.7%. There was no significant difference of either ORR or CR+ nCR rate between bortezomib and thalidomide groups. ② The improvement rate of renal function in bortezomib group and thalidomide group were 87.2% and 60.0% respectively ( P =0.012). The median duration time of renal injury was 45 days in 52 patients with renal function improved, which was significantly shorter compared with 222 days in 17 patients without improvement ( P <0.05). There was no difference of median serum creatinine and creatinine clearance rate between the two groups.③ The median progression-free survival (PFS) and the overall survival (OS) were 18 and 33.5 months, respectively in all patients. The three-year and five-year OS rates were 57% and 17%, respectively. The median PFS was 19 months in bortezomib group, while it was only 12 months in thalidomide group ( P =0.023). The median OS were 36.5 months and 25.5 months respectively, which was no difference ( P =0.285). Conclusions: The newly diagnosed MM patients with renal insufficiency could get higher ORR and the longer PFS using bortezomib-containing regimens as initial therapy. Meanwhile the improvement rate of renal function and the living quality in patients with bortezomib are better compared with those with thalidomide based treatment.

Objective: Bortezomib plus dexamethasone (BD) and bortezomib, epirubicin plus dexamethasone (PAD) are both front-line regimens of multiple myeloma. This study aimed to assess the efficacy and safety of BD versus PAD regimens in multiple myeloma., Methods: All 208 patients with newly diagnosed multiple myeloma using either BD or PAD front-line regimens were enrolled between November 2006 and July 2014. Front-line chemotherapy regimens were 2-7 cycles. Response rates, overall survival, progression-free survival, and adverse effects were retrospectively analyzed., Results: (1) In PAD group, the overall response rate was 82.9% [complete response(CR) 28.6%, very good partial response(VGPR) 12.9%], which was similar as that in BD group [70.3% (CR 26.8%, VGPR 5.1%), P=0.049]. The estimated median progression-free survival was 34.0 months in PAD group versus 25.0 months in BD group (P=0.010). (2) The triplet regimen has a higher accumulated response rate along with chemotherapy cycles, but it didn't show any difference with the doublet regimen. (3) In elderly patients (>65 years old), the overall response rates in two groups had no significant difference (P=0.769), while in patients ≤65 years old, PAD regimen were more effective than BD regimen (P=0.037). (4) Grade 3 and 4 adverse events were recorded with a higher number of patients in the PAD group than those in the BD group., Conclusions: Compared with BD regimen, PAD regimen improves the initial response rates, especially deep responses, as well as progression-free survival in patients with newly diagnosed multiple myeloma. However, more severe toxicities are accordingly higher. In elderly patients, overall response rate, estimated median progression-free survival, and median overall survival are all comparable in both regimens.

Objective: To investigate the effect of CAL-101, a selective inhibitor of PI3Kδ, in combination with bortezomib on the proliferation and apoptosis in human mantle cell lymphoma cell lines Z138, HBL-2 and Jeko-1 in vitro, to explore its mechanisms and provide the foundation for effective treatment strategies against mantle cell lymphoma., Methods: MTT assay was applied to detect the inhibitory effects of CAL-101 and bortezomib either alone or combined on Z138, HBL-2 and Jeko-1 cells. Calcusyn software was used to analyze the synergistic cytotoxicity. Western blot was used to detect the expression of PI3K-p110σ and p-Akt, Akt, p-ERK and ERK proteins after the cells were exposed to different concentrations of CAL-101. Flow cytometry was employed to assess the apoptosis rate. NF-κB kit was used to determine the changes of location of NF-κB P65, and Western blot was applied to detect the level of caswpase-3 and the phosphorylation of Akt in different groups., Results: CAL-101 and BTZ inhibited the proliferation of Z138, HBL-2 and Jeko-1 cells in a dose- and time-dependent manner. CAL-101/BTZ combination induced significantly synergistic cytotoxicity in the MCL cells. The results of Western blot assay showed that CAL-101 significantly blocked the phosphorylation of Akt and ERK in the MCL cell lines. In addition, CAL-101 combined with BTZ induced pronounced apoptosis (P < 0.01). For example, after the Z138 cells exposed to the drugs for 48 h, the apoptosis rates of the control, CAL-101, BTZ and CAL-101 + BTZ groups were: (2.6 ± 1.8)%, (40.0 ± 3.0)%, (34.0 ± 1.0)%, and (67.4 ± 1.0)%, respectively; and when drug treatment was given to HBL-2 cells over 96 h, the apoptosis rates of these four cell groups were (7.4 ± 0.6)%, (30.7 ± 5.7)%, (12.0 ± 1.0)%, and (85.0 ± 4.0)%, respectively. The combination therapy contributed to the enhanced inactivity of nuclear factor-κB (NF-κB) and Akt inactivation in the MCL cell lines (P < 0.05), however, the casepase-3 activity was up-regulated., Conclusions: The combination of CAL-101 and bortezomib is muchmore effective in inhibiting proliferation and promoting apoptosis of mantle cell lymphoma cell lines (Z138, HBL-2 and Jeko-1), which may be mediated through inhibiting PI3K/Akt signaling pathway and the transcription of NF-κB.

Objective: This study was aimed to investigate the therapeutic efficacy and safety of bortezomib in the treatment of follicular lymphoma patients., Methods: According to treatment methods, the 56 follicular lymphoma patients were divided into 2 groups: CHOP group (26 cases) and bortezomib group (30 cases). The patients in CHOP group received the CHOP chemotherapy regimens (cyclophosphamide+ epirubicin+vincristine+prednisolone), the patients in bortezomib group received bortezomib based on CHOP. The clinical curative effect and adverse reaction between the two groups were compared., Results: The short-term efficacy of bortezomib group showed significantly better than that in CHOP group (P < 0.05), the total efficiency in bortezomib group (80%) was significantly higher than that in CHOP group (53.85%) (P < 0.05). The progression free survival of the patients in the bortezomib group was statistically longer than that in the CHOP group (10 months vs 6 months) (P = 0.013). There was no significant differences in the overall survival mediam survival time between these two groups (10 months vs 11 months)(P = 0.107). The occurrence of adverse reactions in the two groups was no significant different (P > 0.05)., Conclusion: Bortezomib combined with CHOP chemotherapy can obviously prolong the progression free survival of patients, and improve the total efficiency without increase of adverse reaction. The benefit to overall survival needs to further extend follow-up observation.

Multiple myeloma (MM) is an uncurable disease. Chemotherapy with standard dose or autologous stem cell transplantation (auto-HSCT) after chemotherapy with high dose is able to induce remission, but relapse still exists. For this reason the ultimate goal of MM treatment is to improve relapse free survival (RFS) and progression free survival (PFS) efficiently. Recently, maintenance therapy made substantial progress in improving progression-free survival and overall survival (OS) of patients with multiple myeloma, especially thalidomide, lenalidomide and bortezomib used in clinic. Here, the latest advances of clinical researches on maintenance therapy of MM are summarized briefly in this review.

Objective: To investigate the proliferation inhibitory role and mechanism of PI3Kδ inhibitor CAL-101 on multiple myeloma (MM) cells, and to provide new therapeutic options for MM treatment., Methods: MM cell lines U266 and RPMI8226 cells were treated with various concentrations of CAL-101. MTT assay and CalcuSyn software were performed to determine the inhibitory effect of CAL-101 and the synergistic effect with PCI- 32765, SAHA (suberoylanilide hydroxamic acid), BTZ (Bortezomib) on MM cells. The protein expression level of p-AKT, p-ERK, AKT, ERK and PI3Kδ processed by CAL-101 were analyzed by Western blot., Results: CAL-101 at concentration of 15, 20, 25, 30 and 40 μmol/L could induce significant dose-dependent proliferation inhibition on U266 cells after treatment for 48 hours. The cell proliferation inhibition rates were (33.54 ± 1.23)%, (41.72 ± 1.78)%, (53.67 ± 2.01)%, (68.97 ± 2.11)% and (79.25 ± 1.92)%, respectively. Similar results were found in RPMI8226 cell line. Western blots showed high expression level of p-AKT, p-ERK, AKT, ERK and PI3Kδ in cell lines and MM primary cells. p-AKT and p-ERK protein expression levels were down-regulated significantly by CAL-101 treatment. Synergistic effect has been verified between CAL-101 and PCI-32765, SAHA and Bortezomib in U266 cell line, and PCI-32765, Bortezomib in RPMI8226 cell line with CI values less than 1., Conclusion: CAL-101 could inhibit proliferation of MM cell lines. High levels of p-AKT, p-ERK, AKT, ERK and PI3Kδ protein expression were observed in both cell lines and primary cells. Down-regulation of p-AKT and p-ERK probably related with the mechanism of CAL-101 in MM cell proliferation inhibition. CAL-101 has significant synergistic effect with PCI-32765, SAHA and BTZ.

A novel poly( 4-vinylphenylboronic acid (VPBA) -co-pentaerythritol triacrylate (PETA)) monolithic column was prepared by thermal-initiated copolymerization of VPBA and PETA in a binary porogen system comprising diethylene glycol and ethylene glycol. The fabricated monolithic column demonstrated good boronate affinity property, which can specifically capture cis-diols containing compounds. We developed such a monolithic column and applied it to enrich active components in Herba Taraxaci and Euonymus acanthocarpus. The extracts of the two traditional Chinese medicines were separated and enriched on microHPLC by the prepared monolith, and the fractions were collected and examined by HPLC. The results showed that the responses of the corresponding peaks were greatly improved, indicating that the poly( VPBA-co-PETA) monolithic column can be efficiently used to enrich active components in traditional Chinese medicines containing cis-diols group.

A novel strategy for the preparation of the organic-inorganic hybrid boronate affinity monolith was developed via the "thiol-ene" click reaction. A thiol group-modified silica monolith was first synthesized via the sol-gel process by the in situ co-condensation with tetramethoxysilane (TMOS) and 3-mercaptopropyltrimethoxysilane (MPTMS) as precursors. Then 3-acrylamidophenylboronic acid (AAPBA) was covalently immobilized on the hybrid monolith via the "thiol-ene" click reaction to form AAPBA-silica hybrid affinity monolith. The reaction conditions for the preparation of AAPBA-silica hybrid affinity monolith were optimized, including the ratio of TMOS to MPTMS, the contents of poly(ethylene glycol) (PEG) and methanol. The morphology and mechanical stability of the boronate affinity monolith were characterized and evaluated by scanning electron microscopy and Fourier-transform infrared spectroscopy. The obtained boronate affinity hybrid monolith exhibited excellent specificity toward the nucleosides containing cis-diols under neutral conditions. It was further applied to the specific capture of the glycoproteins ovalbumin and horseradish peroxidase. The method is novel and reliable, which has a great potential for the preparation of different kinds of the boronate affinity monoliths.

Objective: To determine the difference in gene expression between human multiple myeloma (MM) and normal bone marrow., Methods: cDNA chip was used to detect the mRNA of mononuclear cell from 10 untreated MM patients and 10 cases of normal bone marrow., Results: Of the 2,048 genes, we found 566 different expression genes, of which the expression of 237 genes was higher and 329 lower in MM than in the normal bone marrow., Conclusion: Many genes may be involved in the pathogenesis of MM. cDNA chip technology is an effective tool in the study of tumor related genes.