OBJECTIVETo investigate clonal evolution of abnormal Philadelphia chromosome-negative cells (Ph- CE) after imatinib mesylate therapy in patients with Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+ CML).

METHODSBone marrow cells G-banding karyotype was evaluated every 3 months in 100 patients with Ph+ CML after achieving hematologic responses on the course of imatinib therapy. There were 54 patients in chronic phase (CP), 37 in accelerated phase (AP) and 9 in blast phase (BP).

RESULTSAfter a median follow-up of 32 months (ranged 25-34 months), 11 patients, including 5 cases in CP, 5 in AP and 1 in BP, developed transient, interrupted or continuous Ph- CE after 3 - 29 months on imatinib therapy. Ph- CE emerged at the beginning of Ph+ cells decreasing or after Ph+ cells disappearing. The proportion of Ph- CE, was negatively correlated with the proportion of Ph+ cells (P < 0.05). Ph- CE commonly included +8 (45.5%) and +Y (27.3%). Five patients had additional cytogenetic abnormalities besides Ph+ in Ph- CE. Seven of the patients with Ph- CE achieved a major cytogenetic response while 9 of them achieved a complete hematologic response. One patient with Ph- CE in AP progressed to BP 20 months after the initiation of the therapy while the rests remained in hematologic or cytogenetic responses.

CONCLUSIONPh- CE occurred in about 11% of the patients with Ph+ CML who achieved major or minor cytogenetic responses on imatinib therapy. After a median follow-up of more than 2 years, most of the patients with Ph- CE were in a stable status with no disease progression.

Adult ; Aged ; Antineoplastic Agents ; therapeutic use ; Benzamides ; Clone Cells ; drug effects ; metabolism ; pathology ; Female ; Follow-Up Studies ; Humans ; Imatinib Mesylate ; Karyotyping ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; drug therapy ; genetics ; pathology ; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative ; drug therapy ; genetics ; pathology ; Male ; Middle Aged ; Philadelphia Chromosome ; Piperazines ; therapeutic use ; Pyrimidines ; therapeutic use ; Treatment Outcome

OBJECTIVETo evaluate the efficacy and safety of imatinib in the treatment of adult patients with chronic granulocytic leukemia (CGL) in accelerated phase.

METHODSThirty patients with CGL in accelerated phase were orally administered with imatinib 400 or 600 mg daily for 7 approximately 9 months.

RESULTSHematological responses occurred in 28 of 30 patients (93.3%) in the treatment: 14 (46.7%) had a complete hematological response, 10 (33.3%) had a marrow response, and 4 (13.3%) returned to chronic phase. Bone pain and splenomegaly disappeared soon after the administration of imatinib. Eight patients relapsed 30 approximately 172 days after hematological responses. Six of them received imatinib with daily dose increment to 800 mg. Four of these 6 patients had no response and 2 returned to chronic phase again. The risk factors for relapse were blasts > or = 15% in bone marrow or in peripheral blood, extramedullary leukemia involvement, hemoglobin < 100 g/L before the administration of imatinib, and lack of a complete hematological response after the treatment. Cytogenetic remission occurred in 6 of 27 patients (21.4%) after 3 months treatment: 4 (14.3%) were complete cytogenetic response and 2 (7.1%) major cytogenetic response. Mild non-hematologic adverse effects occurred in most of the patients, but were manageable and tolerable, or disappeared automatically. Severe neutropenia or thrombocytopenia appeared in more than half of the patients.

CONCLUSIONSImatinib has substantial activity and is well-tolerated in the treatment of accelerated phase of CGL.

Adult ; Aged ; Antineoplastic Agents ; therapeutic use ; Benzamides ; Female ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; drug therapy ; Male ; Middle Aged ; Piperazines ; therapeutic use ; Pyrimidines ; therapeutic use ; Treatment Outcome

OBJECTIVESTo assess bone marrow morphologic changes in Philadelphia-chromosome positive chronic myeloid leukemia (Ph(+)-CML) patients treated with Imatinib, and to evaluate the correlation of the morphologic changes with hematological or cytogenetic responses.

METHODSOne hundred and seventeen patients with Ph(+) CML: 54 in chronic phase but failed to interferon-alpha treatment, 41 in accelerated phase, 22 in blastic phase received oral administration of Imatinib 400 or 600 mg once daily for more than 18 months.

RESULTSAll of the patients responded to the treatment, including complete hematological response, bone marrow response and return to chronic phase, bone marrow cellularity and myeloblast count reduced significantly to non-CML picture. Myeloid/erythroid ratio and megkaryocyte count were decreased significantly in most patients in chronic and accelerated phases (P < 0.05). Bone marrow hypoplasia or aplasia was associated with lower cytogenetic response rates in patients in chronic phase (58.8% vs 86.5%, P = 0.035), lower complete hematological response in patients in accelerated phase (26.3% vs 75.0%, P = 0.004), and 6-month overall survival in patients in blastic phase (77.8% vs 16.7%, P = 0.009). Patients in advanced stage obtained non-CML marrow picture in 1 month of treatment had better prognosis. 18-month disease progression rates were lower (25% vs 75%, P = 0.028) and overall survival rates higher (75.0% vs 11.8%, P = 0.004) in patients obtained non-CML picture marrows than in those with CML marrows picture in accelerated phase. Hematological response rate and overall survival of more than 6 months were higher in patients with non-CML marrows picture than those with CML marrows picture (100.0% vs 40.0%, P = 0.017 and 83.3% vs 26.7%, P = 0.046 respectively) in blastic phase.

CONCLUSIONSNormal marrow appearance can be sustained under continuous treatment of Imatinib in CML patients who achieved hematological responses.

Adolescent ; Adult ; Aged ; Benzamides ; Bone Marrow Cells ; cytology ; drug effects ; Female ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; drug therapy ; pathology ; Male ; Middle Aged ; Piperazines ; administration & dosage ; pharmacology ; Pyrimidines ; administration & dosage ; pharmacology ; Treatment Outcome ; Young Adult

OBJECTIVETo observe the pregnancy outcome among patients with chronic myelogenous leukemia (CML) treated with tyrosine kinase inhibitors (TKIs).

METHODSData associated with pregnancy, delivery and neonate from the patients or patient's spouse who conceived while receiving TKIs were collected retrospectively.

RESULTSTwo young female patients (who had been on imatinib therapy for 90 and 91 months, respectively) and spouses of 10 male patients (involving 7 patients who had received imatinib for a median of 60 months and 3 who had received dasatinib for 2.5 months to 7 months, respectively) with median age of 33.5 years (range 26 - 46 years) conceived and gave birth to 12 babies. One woman took imatinib throughout her pregnancy except one month. The other one took imatinib throughout her pregnancy and had breast-fed while on imatinib therapy for nearly half a year postpartum. Among the 12 babies, one was born prematurely with low birth weight and hypospadias (surgical repair after birth), the others were all healthy with no congenital defects. The median age of the children at the date of this report is 17.5 months (range 3 to 101 months), and they all have a normal pattern of growth and development.

CONCLUSIONSConception among patients with CML while receiving TKIs may result in normal pregnancies. The possible effects of TKIs on birth abnormalities cannot be ruled out. It is recommended that childbearing female patients should be advised to practice adequate methods of contraception and should not breast-feed while on TKIs therapy. In cases of accidental pregnancy, risk/benefit evaluations must be carried out carefully on an individual basis. No special precautions apply for male patients being treated with imatinib.

Adult ; Antineoplastic Agents ; therapeutic use ; Benzamides ; Dasatinib ; Female ; Humans ; Imatinib Mesylate ; Infant ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; drug therapy ; Male ; Middle Aged ; Piperazines ; therapeutic use ; Pregnancy ; Pregnancy Outcome ; Protein Kinase Inhibitors ; therapeutic use ; Protein-Tyrosine Kinases ; antagonists & inhibitors ; Pyrimidines ; therapeutic use ; Retrospective Studies ; Thiazoles ; therapeutic use ; Treatment Outcome

OBJECTIVETo evaluate the efficacy and safety of Gleevec (Imatinib) in the treatment of patients with Ph positive chronic myeloid leukemia in chronic phase (CML-CP).

METHODSA total of 54 CML-CP patients in whom previous therapy with interferon-alpha had been failed or untolerated, or relapsed after allogeneic stem cell transplantation (allo-SCT) were treated with 400 mg/d of oral Gleevec for 6 to 11 months.

RESULTFifty-three patients being able to evaluate achieved complete hematological response within 7 to 28 days. Fifty-two (98%) of them remained in this situation at last follow-up. One patient relapsed after 7 months' treatment, and progressed to accelerated phase. Gleevec induced major cytogenetic response in 37 patients (70%) and complete cytogenetic response in 27 (51%). Twenty-nine of 37 patients (78%) achieved major cytogenetic response within 3 months. Grade 3 neutropenia or thrombocytopenia occurred in about 10% of patients, which were manageable or tolerated. Grade 3 or 4 nonhematologic adverse effects were infrequent. Only 1 patient (2%) discontinued treatment because of drug-related adverse events.

CONCLUSIONSGleevec induced high rate of cytogenetic and hematologic responses in patients with CML-CP who failed in previous interferon therapy. The adverse effects were mild and manageable, or no need for treatment.

Adolescent ; Adult ; Antineoplastic Agents ; therapeutic use ; Benzamides ; Female ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; drug therapy ; genetics ; Male ; Middle Aged ; Piperazines ; adverse effects ; therapeutic use ; Pyrimidines ; adverse effects ; therapeutic use

Objective To evaluate the influence of laparoscopic uterine artery ligation on ovarian function. Methods In this retrospective study ,46 patients with laparoscopic myomectomy were selected and randomly divided into Ligation group and Non-Ligation group. The serum concentrations of follicular stimulating hormone (FSH), luteinizing hormone ( LH), estrogen ( E_2) were measured be-fore treatment and 1 ,3 ,6,12 months after treatment. Ovulating functions of ovary were monitored. All results were compared between two groups. Results All patients ovulated after 6 months. There were no significant differences between two groups in the levels of FSH, LH and E_2,.before and after treatment(P>0.05). Conclusions Laparoscopic uterine artery ligation do not affect ovarian function of pa-tients with uterine leiomyoma.

OBJECTIVETo evaluate the result of diagnosis and treatment of intracranial hematoma and multiple injuries caused by road traffic accidents.

METHODSTwenty-eight patients, aged from 1 to 14 years, receiving craniotomy and other surgical treatments were retrospectively reviewed.

RESULTSAmong the 28 cases, 23 cured with the recovery rate of 82.3%, 2 had a sequel of moderate disability, and 3 died from severe brain injury, hemorrhagic shock, and other visceral complications. The clinical symptoms and signs were severe and perplexing. The major characters included: severe head injury, usually combined by multiple injuries, and easy of access to missed diagnosis and misdiagnosis.

CONCLUSIONSThe occurrence of infection is high after traffic accidents as a result of depression of humoral and cellular immunity, long-term bed rest, and fractures of limbs. Hence, on the basis of maintaining vital signs, the management of primary wound is essential to reduce infection and underlying death. In addition to the management of brain injury, concurrent injuries should also be highlighted so as to reach a good result for their patients.

Accidents, Traffic ; Adolescent ; Child ; Child, Preschool ; Craniotomy ; Female ; Humans ; Infant ; Intracranial Hemorrhage, Traumatic ; etiology ; physiopathology ; surgery ; Male ; Multiple Trauma ; etiology ; physiopathology ; surgery

OBJECTIVETo investigate the effects of endothelin-1 (ET-1) overexpression on apoptosis of the rat pulmonary arterial microvascular smooth muscle cells (RPMC) in vitro.

METHODSPrimary RPMC obtained from the pulmonary artery and lung microvasculature were identified by immunofluorescence staining and electron microscope technique. The RPMC was transient transfected with the pMEXneo-ET1 and pCDNA5-FRT-TO-ET1-3'UTR plasmids as well as the empty vector respectively via lipofectamine. Flow cytometry was used to assess the cell cycle and apoptosis of RPMC. Akt and Caspase-3 expressions were detected by Western blot and real time RT-PCR.

RESULTSThe mRNA of ET(A) expression was significantly higher than that of ET(B) receptor in primary RPMC. Flow cytometry analysis revealed significantly reduced apoptosis in ET-1 transfected RPMC compared to that in vehicle transfected RPMC. Overexpression of ET-1 in RPMC also significantly increased the phosphorylation of Akt and reduced the cleaved Caspase-3 expression.

CONCLUSIONSOverexpression of the ET-1 inhibited RPMC apoptosis and activated Akt/PKB-Caspase-3 signaling pathway, which might be responsible for ET-1 induced the pulmonary microvascular arteries remodeling.

Animals ; Apoptosis ; Arteries ; metabolism ; Cells, Cultured ; Endothelin-1 ; metabolism ; Female ; Male ; Muscle, Smooth, Vascular ; cytology ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; Pulmonary Artery ; metabolism ; Rats ; Rats, Sprague-Dawley ; Signal Transduction

Purpose To investigate the expression of miR-200a and PTEN in colorectal carcinoma (CRC) and their relationships with clinicopathologic features. Methods In situ hybridization and immunohistochemistry ( EnVision method) for miR-200a and PTEN were performed in 87 CRCs and normal colorectal tissues distant from tumors. Relationship between expression of miR-200a and PTEN and clinicopathologic parameters of CRC was also analyzed. Results The in situ hybridization showed that the positive expression rate of the miR-200a in CRC was higher than those in normal colorectal mucosa (P<0. 01). The expression of miR-200a was correlated with the degree of tumor differentiation (rs =0. 503, P<0. 01). The immunohistochemistry showed that the positive expression rate of the PTEN in CRC was lower than those in normal colorectal mucosa (P<0. 01). The expression of miR-200a was correlated with the degree of tumor differentiation (rs = -0. 493, P<0. 01). Expression of miR-200a and PTEN was not correlated with age, sex, tumor size, depth of tumor invasion, lymph node metastasis and TNM stage (P>0. 05). The expression of miR-200a had a close negative correlation to that of PTEN in CRC (P<0. 01). Conclusions Overexpression of miR-200a might be associated with the occurrence and development by targeting PTEN, and they could be the indicators in the early diagnosis,treatment and prognosis of CRC.

OBJECTIVESTo evaluate the efficacy and safety of imatinib mesylate (imatinib) for patients with Philadelphia chromosome-positive (Ph+ ) chronic myeloid leukemia (CML) in accelerated and blastic phase.

METHODSSeventy-five Ph+ CML patients in accelerated phase and 49 in blastic phase were treated with 400 mg or 600 mg of imatinib once daily.

RESULTSFor patients in accelerated phase, the cumulative hematological response (HR) rate was 93.3%, including complete HR (CHR) rate 85.3%, and returning to chronic phase (RCP) rate 8% in a median follow-up of 23.0 (1.0 -64.0 ) months. Cumulative major cytogenetic response (MCyR) rate was 33.0%, and complete cytogenetic response (CCyR) rate 28.0%. For patients with CCyR, the major molecular response (MMoR) rate was 47.6%. The estimated 4-year progression-free survival (PFS) rate and overall survival (OS) rate were 48.2% and 52.2% in patients with HR, respectively. Severe leukocytopenia, anemia and thrombocytopenia occurred in 37.3%, 34.6% and 45.3% of all patients, respectively. For patients in blastic phase, the cumulative HR rate was 63.3%, including CHR rate 44.9%, and RCP rate 18.4% in a median follow-up of 4.5 (0.3 -63.0) months. Cumulative MCyR rate and CCyR rate were both 12.2%. For patients with CCyR, the MMoR rate was 33.3%. For patients with HR, the estimated 1-year/2-year PFS and OS rates were 32.8%/15.8% and 46.0%/ 21.0% respectively. Severe leukocytopenia, anemia and thrombocytopenia occurred in 75.5%, 71.4% and 73.5% of all patients, respectively.

CONCLUSIONSThe efficiency of imatinib was decreasing, and severer hematological toxicities increasing with the disease progressing in patients with Ph+ CML. Imatinib improves progression-free survival significantly in most patients in accelerated phase, particularly in those with continuous CCyR or MMoR. The response duration in majority of blastic phase patients is short, and the relapse rate is high.

Adult ; Aged ; Antineoplastic Agents ; therapeutic use ; Benzamides ; Blast Crisis ; drug therapy ; Female ; Follow-Up Studies ; Humans ; Imatinib Mesylate ; Leukemia, Myeloid, Accelerated Phase ; drug therapy ; Male ; Middle Aged ; Piperazines ; therapeutic use ; Prognosis ; Pyrimidines ; therapeutic use ; Treatment Outcome