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Cell mechanics plays an important role in cellular physiological activities. Recent studies have shown that cellular mechanical properties are novel biomarkers for indicating the cell states. In this article, temperature-controllable atomic force microscopy (AFM) was applied to quantitatively investigate the effects of temperature and cellular interactions on the mechanics and morphology of human cancer cells. First, AFM indenting experiments were performed on six types of human cells to investigate the changes of cellular Young's modulus at different temperatures and the results showed that the mechanical responses to the changes of temperature were variable for different types of cancer cells. Second, AFM imaging experiments were performed to observe the morphological changes in living cells at different temperatures and the results showed the significant changes of cell morphology caused by the alterations of temperature. Finally, by co-culturing human cancer cells with human immune cells, the mechanical and morphological changes in cancer cells were investigated. The results showed that the co-culture of cancer cells and immune cells could cause the distinct mechanical changes in cancer cells, but no significant morphological differences were observed. The experimental results improved our understanding of the effects of temperature and cellular interactions on the mechanics and morphology of cancer cells. [ABSTRACT FROM AUTHOR]

Background At present, no effective clinical treatment is available for the late effects of radiation myelopathy. The aim of the present study was to assess the therapeutic effects of human umbilical cord-derived mesenchymal stromal cells (UC-MSCs) in a rat model of radiation myelopathy. Methods An irradiated cervical spinal cord rat model was generated. UC-MSCs were injected through the tail vein at 90, 97, 104 and 111 days post-irradiation. Behavioral tests were performed using the forelimb paralysis scoring system, and histological damage was examined using Nissl staining. The microcirculation in the spinal cord was assessed using von Willebrand factor (vWF) immunohistochemical analysis and laser-Doppler flowmetry. The microenvironment in the spinal cord was determined by measuring the pro-inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the serum and the anti-inflammatory cytokines brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF) in the spinal cord. Results Multiple injections of UC-MSCs through the tail veil decreased the forelimb paralysis, decreased spinal cord histological damage, increased the number of neurons in the anterior horn of the spinal cord, increased the endothelial cell density and the microvessel density in the white matter and gray matter of the spinal cord, increased the relative magnitude of spinal cord blood flow, down-regulated pro-inflammatory cytokine expression in the serum, and increased anti-inflammatory cytokine expression in the spinal cord. Conclusion Multiple injections of UC-MSCs via the tail vein in a rat model of radiation myelopathy significantly improved the microcirculation and microenvironment through therapeutic paracrine effects. [ABSTRACT FROM AUTHOR]

Objective: To analyze the clinical characteristics and long-term prognosis of patients with primary bone lymphoma (PBL)., Methods: The clinical data of 21 patients with PBL treated in our center from 2005 to 2018 were analyzed retrospectively, the clinical characteristics and the factors affecting prognosis of the patients were analyzed., Results: The median age of all the 21 newly diagnosed PBL patients was 40(12-71) years old. Ostealgia was the initial symptom in most of the patients (19/21,90.5%). 42.9%(9/21) of the patients showed single bone lesion only. 571% (12/21) of the patients showed diffuse large B cell lymphoma. 28.6% (6/21) of the patients showed anaplastic large cell lymphoma and 9.5% (2/21) of the patients showed T cell lymphoblastic lymphoma. All the patients received chemotherapy (CHOP or CHOP like regimen, 33.3% plus rituximab) with or without radiotherapy and/or autologous hematopoietic stem cell transplantation (ASCT). 18 patients achieved clinical remission (including 15 for CR and 3 for PR). The median follow-up time was 48 months. The 5-year overall survival rate and progression-free survival rate of the patients were was 67.5% and 63.7%, respectively. The single factors analysis showed that ASCT was the important prognostic factor of PFS, while the single or multiple bone lesion was the factors affecting OS of the patients. There were no statistical differences with the effects of age, sex, stage, ECOG score, LDH level, B symptoms and radiotherapy for the prognosis of patients., Conclusion: Diffuse large B cell lymphoma is the most common pathological type of PBL. Chemotherapy is the main treatment, which can be combined with radiotherapy and/or ASCT. The ASCT and the number of bone lesion are the factors for long time survival of the patients.

Objective: To study the regulatory effect of deubiquitinase MYSM1 on differentiation of B cells to plasma cells., Methods: The interfering and overexpression plasmids of MYSM1 were constructed and then the corresponding lentiviruses were packaged. Human CD19 + B cells were isolated from human peripheral blood with Miltenyi B cell isolation kit. Purified CD19 + B cells were transduced with lentiviruses and then treated with LPS, the CD138 expression was detected by flow cytometry. The expression of transcription factor was determined by quantitative PCR., Results: The differentiation of B cells to plasma cells was enhanced after interfering in MYSM1 expression. Quantitative PCR showed that mRNA levels of Pax5 and Bach2 in cells with interfering in MYSM1 were much lower than their counterpart (P＜0.01), and mRNA levels of Prdm1 and Xbp1 in cells with interfering in MYSM1 were much higher than their counterpart (P＜0.01). On the contrary, the differentiation of B cells to plasma cells was inhibited after the overexpression of MYSM1. Quantitative PCR showed that mRNA levels of Pax5 and Bach2 in cells with MYSM1 overexpression were higher than those in control cells (P＜0.01), and mRNA levels of Prdm1 and Xbp1 in cells with MYSM1 overexpression were much lower than those in their counterpart (P＜0.01)., Conclusion: MYSM1 negatively regulates differentiation of human B cells to plasma cells.

A facile and regioselective base-mediated aerobic oxidative acylation of nitroarenes to access diarylketones under mild conditions has been developed. It features the use of bench-stable and readily available arylacetates as acyl surrogates, and the absence of transition-metals and synthetic oxidants. This protocol involves a cascade CDC/oxidative decarboxylation process.

This study was designed to compare the curative effect, prognosis and safety of different preconditioning regimens for patients who received autologous hematopoietic stem cell transplantation (AHSCT) for malignant lymphoma (ML). The clinical data of 100 ML patients (Sep 1992 to Aug 2010 in 307 Hospital) were retrospectively analyzed, and were divided into two groups by different preconditioning regimens: the high-dose chemotherapy preconditioning group and high-dose chemotherapy/radiotherapy preconditioning group. The overall survival (OS) rate, progress free survival (PFS) rate and adverse effect were analyzed. The results showed that until Feb 2011, the median follow-up was 33.5 months. All patients were engrafted and their hematopoiesis was reconstituted. The median time of WBC recovery up to > 1.0×1.0(9)/L in high-dose chemotherapy preconditioning group and high-dose chemotherapy/radiotherapy preconditioning group were (6.0 ± 0.4) d and (8.2 ± 0.4) d, platelet up to > 20.0×1.0(9)/L in two groups were (7.1 ± 0.8) d and (11.4 ± 2.5) d (P < 0.05). The 3-year OS rate of the two groups were 67.3% and 68.9%. 5-year OS rates of two groups were 62.8% and 60.6%, 10-year OS rates of two groups were 57.6% and 56.2% respectively; 3-year PFS of two group were 63.6% and 63.2%, 5-year of two group were 59.4% and 58.3%, 10-year of two group were 50.8% and 55.3% respectively (P > 0.05). Meanwhile, the incidence of fever, infection, bleeding, secondary cancer between two groups was not significant different (P > 0.05). It is concluded that the hematopoietic reconstitution of high-dose chemotherapy/radiotherapy preconditioning group is later than that of high-dose chemotherapy preconditioning group. However, there is no significant difference in curative effect and prognosis between the two groups.

This paper explored the curative effect of combined modality therapy and extended field radiotherapy for early-stage Hodgkin's Lymphoma. 104 cases of early-stage Hodgkin's Lymphoma from Jan 1987 to Dec 2010 in PLA Hospital 307 were retrospectively analyzed, including 76 cases in combined modality therapy group and 28 cases in extended field radiotherapy group, and the long-term efficacy and toxicity of two therapy modalities were evaluated. The results showed that the median survival time of 104 cases was 85.42 months, the complete remission rates of combined modality therapy and extended field radiotherapy groups were 72.4 and 71.4 respectively (P = 0.924); the overall response rates of combined modality therapy and extended field radiotherapy groups were 97.4 and 96.4 respectively (P = 0.779); the 5-year overall survival (OS) rates in the 2 groups were 89.5 and 89.1 respectively, and the 8-year OS rates of the 2 groups were 81.3 and 70.6. No statistical difference was found in above-mentioned 2 groups. Moreover, the 5-year progression free survival (PFS) rates of these 2 groups were 84.2 and 69.0 (P = 0.04), and 8-year PFS rates of these 2 groups were 80.0 and 55.5 (P = 0.04) respectively, the 5-year relapse rates of these 2 groups were 28.1 and 45.6 (P = 0.023) respectively. It is concluded that the combined modality therapy can raise the PFS rate and reduce the relapse rate as compared with extended field radiotherapy for early-stage Hodgkin's Lymphoma, but there is no difference in the overall survival rate between the 2 groups.

Purpose: The purpose of this study was to investigate the application of double CT imaging to measuring the respiratory movement of small pulmonary tumors during stereotactic ablative radiotherapy (SABR)., Methods: A total of 122 small pulmonary tumors were measured in 45 patients. CT scans were conducted twice in all 122 tumors, once at the end of quiet inhalation and once at the end of exhalation. CT scans were conducted three times including at the end of quiet inhalation, at the end of exhalation and at free breathing in 36 tumors of 17 patients. The displacement of the tumor center in three directions was measured., Results: The 3D motion of 122 tumors was 10.10±7.16 mm. On average, the tumors moved 1.96±2.03 mm (rang, 0-9 mm) in the X direction, 5.19±4.69 mm (rang, 0-19 mm) in the Y direction, and 7.38±6.48 mm (rang, 0-26 mm) in the Z direction. The 3D motion of tumors in the lower lung (13.00±7.64 mm) was significantly greater than that in the upper lung (7.15±5.14 mm), P<0.01. The 3D motion of the lower left lung was 16.35±7.31 mm, which was significantly greater than that of the lower right lung (11.40±7.04 mm), P<0.05. Movement in the anterior lung in the Y direction was significantly larger than in the posterior lung. The motion was 7.49±5.43 mm and 4.04±3.82 mm respectively, P<0.01., Conclusions: Double CT imaging provides accurate data for determining the outline of each target area during stereotactic ablative radiotherapy plane. The location of small pulmonary tumor foci was significantly affected by respiratory and cardiac motion.

This study was aimed to investigate the differences of therapeutic efficiencies, side effects and recovery rates of immune function in refractory lymphoma patients treated with autologous peripheral blood hematopoietic stem cell transplantation (APBHSCT), autologous bone marrow transplantation (ABMT) and combination of APBHSCT with ABMT (APBHSCT + ABMT) by retrospective analysis, and to evaluate the merits and demerits of 3 kinds of transplantation for treatment of refractory lymphoma. 68 patients with malignant lymphoma were treated with autologous hematopoietic stem cells transplantation. Out of 68 patients 10 cases were treated with autologous bone marrow transplantation (ABMT), 46 cases were treated with autologous peripheral blood hematopoietic stem cell transplantation (APBHSCT), and 12 cases were treated with autologous peripheral blood hematopoietic stem cells transplantation combined with autologous bone marrow transplantation (APBHSCT + ABMT). The results indicated that the therapeutic response rates and survival rates at 1, 3, 5 years for each transplant regimen were 90% and 75%, 57.1%, 33.3%; 86.4% and 74.4%, 54.2%, 38.1%; 83.3% and 72.7%, 55.6%, 40%. The times of ANC > or = 0.5 x 10(9)/L were 13, 11 and 9 days, times of platelet >/= 20 x 10(9)/L were 17, 14 and 10 days. The recovery rates of T cell subtypes in patients received ABMT, APBHSCT and APBHSCT + ABMT on 3 months, 6 months, 1 year were (0%, 33.3%, 60%), (10.8%, 32%, 73.9%), (27.3%, 55.6%, 85.7%) respectively. In conclusion, the efficacy and side effects of APBHSCT + ABMT as compared with ABMT and APBHSCT are roughly the same, but ABMT + APBHSCT can result in more rapid hematopoietic reconstitution and less restrictions with contributes to widen choice of transplant regimen for patients with alder age and impaired hematopoietic functions.

Natural phytoestrogens such as the isoflavones genistein and daidzein, and the flavones quercetin exhibit anti-cancer properties. This study was purpose to investigate the anti-proliferative effect of phytoestrogens on acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) cells, and their synergistic antileukemic effect in combination with chemotherapeutic drugs. Optimal dosage of genistein, quercetin and in combination with chemicals for leukemia cells were determined by experiments. Cell viability, apoptosis induction and cell cycle arrest were detected by trypan blue staining, MTT assay, optical microscopy, flow cytometry (FCM). The schedule treatment of combination of genistein and chemicals was determined. The results showed that genistein exhibited a dose- and time-dependent inhibitory effect on cell proliferation in NB4 and HL-60 cells, induced apoptosis and cell cycle arrest in G2/M phase. Quercetin had evident inhibitory effect on the proliferation of K562 and K562/A cells. The combination of genistein and chemicals exerted a synergistic effect on cell growth inhibition. In conclusion, this study demonstrated the synergistic antileukemic effect of genistein with chemotherapeutic drugs on leukemic cells. This combination appears to be a new idea for the clinical novel treatment of leukemia.

Tumor angiogenesis is a complicated process in which VEGF and the members of Ang family have been proposed to play an important role. Ang family is the only vascular growth factor family including activators and inhibitors. They can all bind with specific tyrosine kinase receptor Tie-2 and participate in angiogenesis. Vascular endothelial growth factor (VEGF) is secreted by tumor cells and coordinates with Ang to promote angiogenesis. Further research on the structure and functional mechanism of VEGF and Ang will contribute to develop a new type of antiangiogenesis medicine, which might have good perspect in clinical practice. In this paper, the structure and action mechanism of Ang family and its receptor Tie-2, the application of Ang family and Tie in tumor therapy, and the synergic mechanism between Ang and VEGF were summarized.

Objective: To compare the efficacy and safety of daily administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF), and a single subcutaneous injection of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF), a sustained-duration rhG-CSF, in chemotherapy-induced neutropenia., Methods: In the present randomized, open-label, match and cross-over study, enrolled 104 patients with previously untreated non-small cell lung cancer (NSCLC), breast cancer or non-Hodgkin's lymphoma and with normal bone marrow function from 13 centers were randomly divided into 2 matched groups, AB and BA group. Each patient received two cycles of chemotherapy of identical regimen. In the study cycle, the patients received a single subcutaneous injection of PEG-rhG-CSF 100 microg/kg on day 3; and in control cycle, daily subcutaneous infection of rhG-CSF 5 microg x kg(-1) x d(-1) began on day 3 and continued for 14 days or until the absolute neutrophil count (ANC) became > or = 5.0 x 10(9)/L twice after it decreased to the nadir. Efficacy and safety parameters were monitored., Results: The incidence rates of ANC < 1.5 x 10(9)/L in the 103 evaluable study cycles and 100 evaluable control cycles were 30.00% and 20.00% with the duration of 2.39 days and 2.35 days respectively. The incidence rates of grade 3 neutropenia were 7.77% and 7.00%; and that of grade 4 neutropenia were 5.80% and 4.00% respectively in the trial and control cycles. However, all the difference mentioned above did not reached statistical significance. None of the patients experienced febrile neutropenia. The ANC nadir was (7.55 +/- 5.25) x 10(9)/L and (8.42 +/- 5.57) x 10(9)/L (P = 0.257) respectively after receiving PEG-rhG-CSF and rhG-CSF. Compared with that of rhG-CSF group, the ANC profile of PEG-rhG-CSF group exhibited limited "overshoot" of neutrophils after the nadir. Subgroup analysis according to disease type yielded similar results. The safety profiles of the PEG-rhG-CSF and rhG-CSF groups were similar. Musculoskeletal pain or arthralgia occurred in 16.5% of the study cycles and 26.00% of the control cycles (P = 0.963), mostly mild or moderate. Other adverse effects such as fever, fatigue, dizziness, gastrointestinal effects and injection-site pain, were transient and easily manageable., Conclusion: A single subcutaneous injection of PEG-rhG-CSF 100 microg/kg provides neutrophil support and a safety profile comparable to regimen of daily subcutaneous injection of rhG-CSF 5 microg x kg(-1) x d(-1) in Chinese patients receiving a variety of myelosuppressive chemotherapy regimens.

Objective: To study the correlation between clinical prognosis and clinicopathologic features, origin and cell proliferous index of diffuse large B-cell lymphoma (DLBCL) in China., Methods: The data of 60 cases of DLBCL were collected with the study of international prognostic index (IPI) and the follow-up results. Immunohistochemistry stain was used to check the expression of CD(45)RO, CD(3), CD(20), CD(79)a, CD(45)RA, Ki-67, p53 and bcl-6., Results: The ratio of male to female is 1.73 and the average age is 53.1. In 53.3% cases lymph node were involved (32/60), gastric intestinal tract and tonsil were the most common extranodal sites of involvement. 23 patients 38.3% died during follow-up, the longest survival period lasting 108 months.16 died in the first year after establishment of diagnosis (16/23, 69.6%). IPI is an independent prognostic index; the lower the index, the better the prognosis (P = 0.0102). Positive incidence of CD(20), CD(79)a and CD(45)RA was 91.5%, 73.7% and 58.3%. Ki-67, p53, bcl-6 were expressed in some cases (48/53, 90.6%; 26/46, 56.5%; 21/41, 51.2%). The expression of bcl-6 protein was somewhat related with prognosis (P = 0.0049), but the expression of p53 was not (P = 0.5948)., Conclusions: The clinicopathologic features of DLBCL are similar in the East and the West. It is highly aggressive tumor. Most of the cases died in the first year after establishment of diagnosis. IPI can be used to predict the clinical outcome. The expression of bcl-6 protein was somewhat related with clinical prognosis, but that of p53 was not.

The purpose of this study was to evaluate whether the DNA vaccine containing idiotypic gene fragment of human B-cell lymphoma cell line Namalwa could elicit the specific anti-idiotypic immune response in vivo. The candidate gene fragment of the lymphoma cell, variable region of heavy chain (VH) of the membranous immunoglobulin, was amplified using Ig superfamily primers by means of RT-PCR. Also, the intact cDNA of murine monocyte chemoattractant protein (MCP-3) was cloned and used as the adjuvant molecular. The two gene fragments of VH and MCP-3 were fused together by 8aa linker peptide with recombinant PCR. Subsequently, the fusion gene fragment was cloned into eukaryonic expression vector pcDNA3.1 to construct DNA vaccine plasmid. Prior to the immunization, the transient transfection coupled with RT-PCR was performed to prove that the recombinant plasmid could express in eukaryonic cells in right way. Then two groups of mice were immunized by intramuscular injection with DNA vaccine and mock plasmid pcDNA3.1 respectively. Three times of injection were performed with 100 micro g plasmid respectively at the beginning of the experiment and 2, 4 weeks after the first injection for all the groups. FACS analysis was chosen to detect the antibodies recognizing lymphoma cells at different time following vaccination. The results demonstrated that specific anti-idiotypic antibody could be detected in the group of DNA vaccine immunized mice as early as eight weeks after the first immunization. Further test demonstrated that the anti-idiotypic antibody could maintain for at least twenty weeks with high titer. Anti-idiotypic antibodies were elicited in three of five mice of the DNA vaccine immunized group. The Abs of DNA vaccine immunized mice could only recognize Namalwa cell line instead of another unrelated human cell line A549. There is no cellular response detected in the DNA vaccine immunized mice. It is concluded that the DNA vaccine containing fused MCP3-VH sequence could elicit specific anti-idiotypic antibody against B-cell lymphoma in vivo and could be used in further study of DNA vaccine against B-cell lymphoma. The results would provide the basis for further studies and optimization of this therapeutic strategy on patients with B-lymphoproliferative disease.

The lymphochip is a special DNA chip which is used to monitor the gene expression profiling of malignant lymphoma. The basic principle, technological procedure and types of lymphochip were briefly reviewed in the article. The article emphatically introduced the advance of lymphochip implication which was used to identify the molecular diagnosis, distinguish the subtypes and research the morbific mechanism of malignant lymphoma. The aspects of development and problems in lymphochip study were discussed.

Objective: To determine the clinical results of selected CD34(+) cell autologous transplantation in advanced malignant tumors., Methods: After pretreatment, fifteen patients aged 12 - 70 (49.5) years with various Stage III or IV malignant tumors were given the sorted CD34(+) cells collected by magnetic-activated cell sorting (Clini MACS, Milteny Biotech, Germany)., Results: Peripheral blood progenitor cells (PBPC) from the patients were mobilized by chemotherapy and G-CSF 5 micro g/kg per day. CD34(+) cells gave 2.0 - 5 log depletion after cell sorting, with a median yield of CD34(+) selected cells of 2.4 (0.15 - 12.03) x 10(6)/kg. It gave a median recovery of 64 (52 - 81.4)% and median purity of 98.2 (83.2 - 99.7)%. The median time of neutrophil recovery > 1.0 x 10(9)/L and platelet recovery > 20 x 10(9)/L post-transplantation were 14 (8 - 26) days and 13 (11 - 35) days, respectively. On follow-up of 2 - 33 (11) months, the event-free survival rate was 53.3% (8/15) and the overall survival rate was 66.7% (10/15)., Conclusion: Transplantation of autologous selected PBPC CD34(+) cells gives prompt and stable engraftment. Selected CD34(+) cell transplantation, being a safe approach, may improve the clinical outcome even in patients with advanced malignant tumors.