Objective To investigate the clinical effect of preoperative neoadjuvant chemotherapy by thalidomide combined with gefitinib for non-small cell lung cancer (NSCLC) patients and provide clinical basis for NSCLC therapy.Methods From 2011/1 to 2013/1,we collected 160 NSCLC cases in our hospital and divided them into 2 groups randomly,80 cases in control group and 80 cases in observation group.The patients in the control group were treated with conventional surgical treatment and patients in the observation group were treated with preoperative neoadjuvant chemotherapy by thalidomide combined with gefitinib before surgery.The clinical effects,the 6 months and 1 year survival rates,and the toxicity effects were observed,and the clinical effects and survival rates between the 2 groups were compared.Results The observation group had a therapeutic efficiency ratio (TER) of 80.0％ which was significantly higher than the control group (50.0％),and the difference was statistically significant (P＜0.05).The 6 months survival rate and 1 year survival rate were 97.5％ and 92.5％,which were both significantly higher than those of control group (87.5％ and 77.5％),and all differences were statistically significant (P＜0.05).The toxicity effects of observation group were lower.Conclusions Preoperative neoadjuvant chemotherapy by thalidomide combined with gefitinib for NSCLC therapy is effective and safe,which is worthy of study and further application in clinical treatment..

Special emphasis about cancer metastasis was concentrated on tumor cells themselves, and we usually considered the ability of migration and invasion was the final decider. Recently, bewaring of tumor microenvironment is a fundamental determinant in metastasis has become the most outstanding breakthrough. Considerable "microbes" in the microenvironment are closely linked with tumor metastatic behaviors, and the major proportion of them is tumor-associated macrophages (TAMs). Actually, TAMs conserve immediate "cross-talk" with cancer cells throughout tumor development. It is generally accepted that TAMs have mostly pro-tumoral functions and play an important role in several stages of tumor progression. This progression involves a series of events that leads from the primary site to the metastatic site, including tumor cell growth, angiogenesis, migration, invasion, intravasation and finally extravasation at distant site where the process begins again (metastasis). Thereby, TAMs has attracted substantial attentions in recent years and could become a promising therapeutic strategy. In this review, we focus on the multi-functions of TAMs in cancer and certain drugs targeting TAMs for cancer treatment those are under experimental research procedures or have even been entered human clinical tests.
Animals ; Gene Expression Regulation, Neoplastic ; Humans ; Macrophages ; metabolism ; Neoplasms ; pathology ; Neovascularization, Pathologic ; metabolism ; pathology

This study was purposed to investigate the effect of adenovirus-mediated transfer of PDCD5 gene on apoptosis of K562 cells induced by etoposide. Recombinant adenovirus PDCD5 (Ad-PDCD5), control vectors Ad-null and Ad-eGFP were constructed by AdMax vector system respectively. After K562 cells were transfected by Ad-PDCD5, Ad-null or Ad-eGFP with different multiplicity of infection (MOI), the expression level of the PDCD5 gene was examined by RQ-RT-PCR assay. The effects of etoposide in combination with Ad-PDCD5 on the proliferation and apoptosis of K562 cells were measured by using MTT assay and flow cytometry with Annexin-V-FITC/PI dual labeling technique, respectively. The results showed that the transfection efficiencies of Ad-eGFP in K562, Jurkat and CEM cells ranged from 60% to 86%. Expression level of PDCD5 gene in K562 cells was evidently increased following transfection with Ad-PDCD5. The Ad-PDCD5 synergistically enhanced the apoptotic percentage of K562 cells induced by VP-16, as compared with that of Ad-null + VP16 and VP-16 alone respectively. It is concluded that Ad-PDCD5 may be a potential agent for enhancing the chemotherapy effect.
Adenoviridae ; genetics ; metabolism ; Antineoplastic Agents, Phytogenic ; pharmacology ; Apoptosis ; drug effects ; Apoptosis Regulatory Proteins ; genetics ; metabolism ; Etoposide ; pharmacology ; Humans ; K562 Cells ; Neoplasm Proteins ; genetics ; metabolism ; RNA, Messenger ; metabolism ; Recombinant Proteins ; genetics ; metabolism ; Transfection

OBJECTIVETo evaluate levels of common specific fusion transcripts M-bcr-abl, m-bcr-abl, TEL-AML1, AML1-ETO, PML-RAR alpha, CBF beta-MYH11 in untreated leukemia patients.

METHODSSpecific fusion transcript levels were detected by TaqMan-based real-time quantitative RT-PCR technique in a total of 208 samples, including 195 bone marrow samples from 50 M-bcr-abl(+) chronic phase-chronic myeloid leukemia (CML-CP), 10 M-bcr-abl(+) acute lymphoblastic leukemia (ALL), 19 m-bcr-abl(+) ALL, 11 TEL-AML1(+) ALL, 30 AML1-ETO(+) acute myeloid leukemia (AML), 58 PML-RAR alpha(+) acute promyelocytic leukemia (APL) and 17 CBF beta-MYH11(+) AML patients and 13 peripheral blood samples from 13 M-bcr-abl(+) CML-CP patients. abl was chosen as internal control gene. Fusion transcript level was calculated as fusion transcript copies/abl transcript copies in percentage.

RESULTSBone marrow and peripheral blood samples of CML-CP patients had similar M-bcr-abl fusion transcript levels (median 30% vs 35%, P > 0.05). M- and m-bcr-abl (median 64% vs 54%) levels were similar in ALL patients (P > 0.05), M-bcr-abl level was significantly higher in ALL than CML-CP patients(P < 0.001). Median TEL-AML1 level was 228% in ALL patients. Among AML patients, AML1-ETO level was significantly higher than CBF beta-MYH11 and PML-RAR alpha levels (median 388% vs 145%, 388% vs 47%, all P < 0.001), CBF beta-MYH11 level was significantly higher than PML-RAR alpha level (P < 0.001). Fusion transcript levels of L-, V- and S-type PML-RAR alpha were 45%, 44% and 55%, respectively. L-type was significantly lower than S-type (P = 0.04).

CONCLUSIONSFusion transcript levels in untreated leukemia patients were different and patient-to-patient variations did exist. Detection of fusion transcript levels in untreated leukemia patients not only provides baseline for minimal residual disease monitoring and treatment evaluation but also enable the comparison in inter-laboratory data.

Adolescent ; Adult ; Bone Marrow Cells ; metabolism ; Child ; Child, Preschool ; Core Binding Factor Alpha 2 Subunit ; genetics ; Female ; Fusion Proteins, bcr-abl ; genetics ; Humans ; Leukemia ; genetics ; Male ; Middle Aged ; Oncogene Proteins, Fusion ; genetics ; RUNX1 Translocation Partner 1 Protein ; Reverse Transcriptase Polymerase Chain Reaction ; methods ; Transcription, Genetic

OBJECTIVETo study the effect of aqueous extract of several kinds of herbs on human platelet aggregation and expression of P-selectin in vitro.

METHODSBlood was collected from volunteers. Effects of the prepared water extracts of herbs on platelet aggregation were monitored on a Packs-4 aggregometer. The fluorescence intensity of water extracts of Caulis Spatholobi, Flos Carthami and Rhizoma Curcumae on the expression of P-selectin in human platelets of healthy persons was measured with flow cytometry.

RESULTSOut of several herbs investigated, Flos Carthami and Rhizoma Curcumae potently inhibited platelet aggregation after incubation with platelet-rich plasma (PRP) for 15 min. Caulis Spatholobi Flos Carthami and Rhizoma Curcumae inhibited adenosine-5'-diphosphate (ADP) or platelet activating factor (PAF)-induced platelet aggregation in PRP in a dose-dependent manner. In contrast to Flos Carthami and Rhizoma Curcumae, Caulis Spatholobi could not inhibit thrombin-induced platelet aggregation. Despite its inability to inhibit thrombin-induced platelet aggregation in PRP, Caulis Spatholobi had a greater anti-aggregating activity in PRP induced by ADP or PAF. Caulis Spatholobi and Flos Carthami showed significant inhibitory effects on the expression of P-selectin.

CONCLUSIONSCaulis Spatholobi, Flos Carthami and Rhizoma Curcumae have potent anti-platelet properties, and their inhibitory actions are mediated via different mechanisms. Caulis Spatholobi inhibited ADP-induced platelet aggregation but not by thrombin, indicating that its mechanism of action might be independent of the thromboxane pathway. The effect of Caulis Spatholobi and Flos Carthami were associated with suppressing the expression of P-selectin.

Adult ; Blood Platelets ; drug effects ; metabolism ; Curcuma ; chemistry ; Fabaceae ; chemistry ; Humans ; P-Selectin ; metabolism ; Plant Extracts ; chemistry ; pharmacology ; Plants, Medicinal ; chemistry ; Platelet Aggregation ; drug effects ; Platelet Function Tests ; Water ; chemistry ; Young Adult

OBJECTIVETo evaluate the value of real time quantitative RT-PCR (Q-PCR) for monitoring bcr-abl mRNA levels in chronic myeloid leukemia (CML) patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT).

METHODSQuantification of bcr-abl mRNA was performed on 316 bone marrow samples from 112 patients with CML after HSCT by Q-PCR using the TaqMan probe system. The bcr-abl mRNA level was normalized by control gene abl. Cytogenetic response was evaluated with fluorescent in-situ hybridization (FISH).

RESULTSThe reproducible sensitivity of Q-PCR was 5 copies. The coefficients C(T) of interassay and intraassay variation for abl and bcr-abl were all below 2.0%. 289 bone marrow samples were collected from 101 CML patients who achieved a sustained complete cytogenetic response (CCyR) one month post allo-HSCT in a period of 6 - 60 months (median 12 months) at different intervals. In general, the median bcr-abl levels gradually decreased with the prolongation of time after HSCT: the median bcr-abl levels were 0.035% (0 - 0.406%) at 1 month post allo-HSCT (+ 1 month), 0.006% (0 - 0.683%) at +3 month, 0% (0 - 0.225%) at +6 month and remained 0% till +24 months. The highest level in CCyR patients detected at + 6 month was 0.068%. The bcr-abl mRNA level was decreased by 3 log in sustained CCyR patients at + 1 month compared with the newly diagnosed CML-CP patients (33.0%, data unpublished). On the contrary, Q-PCR results ranged from 0.12% to 13.45% in 8 cytogenetic non-responders or relapsed patients post allo-HSCT. Among them, 5 patients' samples were collected 1 - 2 months before cytogenetic relapse, the results were ranged from 0.09% to 3.42%. If 0.09% was assumed 0.09% as a threshold, 9 sustained CCyR patients (8.9%) were tested once higher than that within 6 month after HSCT but decreased to 0% eventually. 2 blast crisis patients achieved CCyR within 1.6 and 3 months after HSCT, but hematological relapse occurred after 1 and 1.5 months, and their bcr-abl mRNA levels increased dramatically from 0% and 0.14% to 46.9% and 75.9% respectively.

CONCLUSIONSQ- PCR is a sensitive, precise and reliable technique, and can be used to monitor CML patients post allo-HSCT regularly. Patients in blast phase of CML should be monitored more frequently.

Adolescent ; Adult ; Bone Marrow Cells ; metabolism ; Child ; Female ; Fusion Proteins, bcr-abl ; biosynthesis ; genetics ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; metabolism ; surgery ; Male ; Middle Aged ; RNA, Messenger ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; methods

The aim of this study was to investigate the gene expression of programmed cell death 5 (pdcd5) in plasma and bone marrow cells from patients with multiple myeloma (MM). Enzyme liked immunosorbent assay (ELISA) and real-time quantitative reverse transcription polymerase chain reaction (RQ-RT-PCR) were used to examine pdcd5 gene expression in plasma and marrow cells in 45 MM patients and 20 normal controls. The results showed that serum levels of PDCD5 protein in 45 MM patients were lower significantly compared with the normal controls and 20 responsive patients after chemotherapy, their plasma levels were (16.91 +/- 0.28) ng/ml, (19.11 +/- 0.29) ng/ml and (17.94 +/- 0.154) ng/ml respectively (p < 0.05). The pdcd5 gene expression levels detected by RQ-RT-PCR in 45 MM patients were lower significantly compared with the normal controls, their pdcd5 gene expression levels were 0.64 +/- 0.47 and 1.28 +/- 1.21 respectively (p < 0.05). It is concluded that the PDCD5 protein expression levels are low in patients with MM. These findings suggest that abnormal expression of pdcd5 may be involved in the pathogenesis of MM.
Adult ; Aged ; Apoptosis Regulatory Proteins ; genetics ; Bone Marrow Cells ; pathology ; Case-Control Studies ; Female ; Gene Expression ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; genetics ; pathology ; Neoplasm Proteins ; genetics ; Young Adult

This study was aimed to detect the expression level of cmtm 5 (CKLF-like MARVEL transmembrane domain containing member 5) gene in the bone marrow cells from patients with multiple myeloma (MM), and to investigate the correlation between the expression level of cmtm5 and various clinical characteristics. Real-time quantitative reverse transcription polymerase chain reaction (RQ-RT-PCR) was used to measure the expression levels of cmtm5 gene in the bone marrow cells collected from MM patients, and the MM cell lines, namely, RPMI8226 and CZ1 cells. The normal donor marrow specimens were used as the reference. The ratio of cmtm5 copy number to abl (Abelson murine leukemia viral oncogene homolog) gene copy number was used for indicating the expression level. The results showed that the expression level of cmtm5 gene was significantly down-regulated in bone marrow cells of 51 untreated or relapsed/refractory MM patient as compared to those of normal donor marrow cells (0.047+/-0.062 for the untreated or relapsed/refractory MM patients versus 0.255+/-0.333 for the normal, p<0.01). According to the International Staging System (ISS), the cmtm5 expression level in marrow cells of patients in ISS III stage was significantly lower than that in patients in ISS I stage (0.034+/-0.034 for the ISS III stage versus 0.103+/-0.109 for ISSI stage, p<0.01). Similarly, lower expression levels of cmtm5 gene were also found in two human MM cell lines (0.014+/-0.009 for RPMI8226 cells and 0.004+/-0.006 for CZ1 cells). After the MM patients were effectively treated, their expression levels of cmtm5 gene significantly increased (0.020+/-0.005 for the untreated patients versus 0.227+/-0.038 for the effectively treated patients, p<0.01). A significant negative correlation was observed between the expression level of cmtm5 gene and the number of bone marrow plasma cells (r=-0.307, p<0.05). However, the correlation was not found between the expression level of cmtm5 gene and the clinical characteristics, such as gender, age, hemoglobin level, or M-protein level, etc. It is concluded that the expression level of cmtm5 gene is abnormally lower in the bone marrow cells from the MM patients, and are associated with ISS stages. Furthermore, the expression level of cmtm5 gene is negatively correlated with the number of bone marrow abnormal plasma cells in MM patients, which suggests that the abnormally lower expression of cmtm5 may be involved in the pathogenesis of the MM patients.
Adult ; Aged ; Aged, 80 and over ; Bone Marrow Cells ; metabolism ; pathology ; Case-Control Studies ; Chemokines ; genetics ; metabolism ; Female ; Humans ; MARVEL Domain-Containing Proteins ; Male ; Middle Aged ; Multiple Myeloma ; metabolism ; pathology ; Neoplasm Staging ; Tumor Suppressor Proteins ; genetics ; metabolism ; Young Adult

OBJECTIVETo investigate the expression of Notch1 on the membrane of bone marrow CD38(+)CD138(+) plasma cells in the patients with multiple myeloma (MM), and explore the importance of Notch signaling pathway in the formation and progression of MM.

METHODSThirty three MM patients and 15 healthy controls were enrolled in this study. The expression of Notch1 on the membrane of bone marrow CD38(+)CD138(+) and CD38(+)CD138(-) plasma cells were analyzed by flow cytometry. The clinical data of MM patients were also analyzed.

RESULTSThe ratio of Notch1 on the membrane of CD38(+)CD138(+) plasma cells of MM patients was (60.21 ± 25.06)% which was significantly higher than those of CD38(+)CD138(-) plasma cells of MM patients (39.84 ± 18.94)% (P = 0.000) and controls (38.34 ± 19.39)% (P = 0.004). There was no statistical difference between the two latter groups (P > 0.05). The expression of Notch1 on CD38(+)CD138(+)plasma cells from 24 newly diagnosed MM patients was correlated to the level of malignant plasma cells in there bone marrow (r = 0.914, P = 0.000), serum level of lactate dehydrogenase (LDH) (r = 0.754, P = 0.007), and β(2)-MG(r = 0.716, P = 0.013). The ratio of Notch1 on the membrane of CD38(+)CD138(+) plasma cells of MM patients who had renal dysfunction was correlated to their abnormal serum creatinine levels. The expression of Notch1 on CD38(+)CD138(+) plasma cells from 17 MM patients who received VD (bortezamib and dexamethasone) chemotherapy was correlated to the ratio of plasma cell reduction after the first VD chemotherapy (r = 0.842, P = 0.000).

CONCLUSIONThe expression of Notch1 on the membrane of CD38(+)CD138(+) plasma cells of MM patients was significantly higher than those of CD38(+)CD138(-) plasma cells of MM patients and controls. Notch1 overexpressed plasma cells were sensitive to the early VD therapy, and correlated to the progression and long term outcome of MM.

ADP-ribosyl Cyclase 1 ; immunology ; Adult ; Aged ; Aged, 80 and over ; Bone Marrow ; metabolism ; Case-Control Studies ; Cell Count ; Female ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; immunology ; metabolism ; Plasma Cells ; immunology ; metabolism ; Prognosis ; Receptor, Notch1 ; metabolism ; Syndecan-1 ; immunology

OBJECTIVETo explore a good way of the reconstruction of severe tibial shaft fractures by using different flaps and external fixators.

METHODSEighty-five patients of Type IIIC tibial shaft fractures with average age of 42.5 years were treated in our hospital from 1990 to 2005. Injuries were caused by motorcycle accidents in 66 patients, by machine accidents in 16 patients, and by stone bruise in 3 patients. The management procedures consisted of administration of antibiotics, serial debridment, bone grafting if needed, application of different flaps, such as free thoracoumbilical flaps, fasciocutaneous flaps, saphenous neurocutaneous vascular flaps, sural neurocutaneous vascular flaps and gastrocnemius muscular flaps, and different external fixations, for instance, half-ring fixators, unilateral axial dynamic fixators, AO fixators, Weifang fixators, and Hybrid fixators. The average follow up was 6.3 years.

RESULTSAll flaps survived. Eighty-three cases had bone healed. The average bone healing time of different external fixations was 5.5 months in 47 cases with half-ring fixators, 9.2 months in 4 cases treated with unilateral axial dynamic fixators, 8.5 months in 6 cases with AO fixators, 10.7 months in 16 cases with Weifang fixators, and 7.8 months in 10 cases with assembly fixators. Except half-ring fixation, other fixations all needed necessary bone graft. Two cases treated with unilateral axial dynamic fixators had nonunion of bone and developed osteomyelitis. The wounds healed after the removal of the fixators and immobilization by plaster. The last follow up examination showed ankle and knee motion was normal and no pain was noted.

CONCLUSIONSThe combination of half-ring external fixators with various flaps provides good results for Type IIIC tibial shaft fractures.

Adolescent ; Adult ; Aged ; Bone Transplantation ; Child ; Child, Preschool ; Debridement ; Female ; Fracture Fixation ; methods ; Fracture Healing ; Humans ; Leg Injuries ; surgery ; Male ; Middle Aged ; Reconstructive Surgical Procedures ; methods ; Retrospective Studies ; Surgical Flaps ; Tibial Fractures ; surgery ; Treatment Outcome