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 investigate the expression and regulation mechanism of mismatch repair (MMR) genes in chronic myeloid leukemia (CML).

METHODSExpression of MMR genes hMSH2, hMSH3, hMSH6, hMLH1 and hPMS2 mRNAs in 62 CML patients and K562 cell line were detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). Expression of bcr-abl mRNA and MMR genes mRNA were detected by RT-PCR in 26 CML patients with allogeneic peripheral blood stem cell transplantation (allo-PBSCT) and 4 CML patients on imatinib treatment. Expression of bcr-abl mRNA was detected by RT-PCR and tyrosine phosphorylation of BCR-ABL fusion protein by Western blot.

RESULTSExpression of hMSH2, hMSH3 and hMLH1 mRNA was significantly lower in CML and K562 cells than in normal control (P < 0.05). In 26 CML with allo-PBSCT and 4 CML patients on imatinib treatment, expressions of hMSH2, hMSH3 and hMLH1 mRNA was enhanced while expression of bcr-abl mRNA decreased. In CML MNC after imatinib treatment and in K562 cells, expression of hMSH2, hMSH3 and hMLH1 mRNA was enhanced while tyrosine phosphorylation of BCR-ABL fusion protein decreased.

CONCLUSIONExpressions of hMSH2, hMSH3 and hMLH1 mRNA were down-regulated by bcr-abl fusion gene.

Adult ; Aged ; Antineoplastic Agents ; pharmacology ; Benzamides ; DNA Mismatch Repair ; Female ; Fusion Proteins, bcr-abl ; genetics ; metabolism ; Gene Expression ; Gene Expression Regulation, Neoplastic ; Humans ; Imatinib Mesylate ; K562 Cells ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; genetics ; Male ; Middle Aged ; Piperazines ; pharmacology ; Pyrimidines ; pharmacology ; RNA, Messenger ; genetics ; Reverse Transcriptase Polymerase Chain Reaction

This study was aimed to investigate the expression and regulation mechanism of DNA-dependent protein kinase catalylic subunit (DNA-PKcs) in chronic myeloid leukemia (CML) and its role in blast crisis of CML. Expression of DNA-PKcs mRNA was detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and DNA-PKcs protein by Western blot in 62 CML patients and K562, as compared to those of 23 normal individual controls. In 26 CML patients received allogeneic peripheral blood stem cell transplantation (allo-PBSCT) and 4 CML patients treated with imatinib, the expression of bcr-abl mRNA and DNA-PKcs protein was detected by RT-PCR and Western blot, respectively. After treatment with imatinib in mononuclear cell (MNC) of CML patients and K562 in vitro, expression of DNA-PKcs mRNA was detected by RT-PCR and DNA-PKcs protein level, tyrosine phosphorylation of bcr-abl fusion protein were detected by Western blot. The results showed that the expression of DNA-PKcs protein was significantly lower in CML and K562 than those in normal control (P<0.05). In 26 CML patients received allo-PBSCT and 4 CML patients treated with imatinib, the expression of DNA-PKcs protein was enhanced while the expression of bcr-abl mRNA decreased. After treatment of MNC of CML and K562 with imatinib in vitro, the expression of DNA-PKcs protein was enhanced while tyrosine phosphorylation of bcr-abl fusion protein decreased. It is concluded that the expression of DNA-PKcs protein is down-regulate by bcr-abl fusion gene, and the bcr-abl fusion gene down-regulate the expression of DNA-PKcs protein by post-transcriptional mechanism; the decrease of DNA-PKcs protein expression may be one of mechanisms underlying the acute transformation of CML.
Adult ; Aged ; Benzamides ; Bone Marrow Cells ; metabolism ; DNA-Activated Protein Kinase ; biosynthesis ; genetics ; Female ; Fusion Proteins, bcr-abl ; biosynthesis ; genetics ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; genetics ; therapy ; Male ; Middle Aged ; Peripheral Blood Stem Cell Transplantation ; Piperazines ; therapeutic use ; Pyrimidines ; therapeutic use ; RNA, Messenger ; biosynthesis ; genetics

After antibiotic prophylaxis with metronidazole and levofloxacin, a transrectal sextant biopsy was performed under the guide of transrectal ultrasonography (TRUS) for a 75-year-old suspicious patient with prostate adenocarcinoma. Although antibiotics were also given after this procedure, the patient still developed fever, anxious, agrypnia and headache. Blood cultures remained negative. Lumbar puncture was performed and was consistent with Escherichia coli bacterial meningitis.
Adenocarcinoma ; pathology ; Aged ; Anti-Infective Agents ; administration & dosage ; Anti-Infective Agents, Urinary ; administration & dosage ; Biopsy ; adverse effects ; Escherichia coli Infections ; drug therapy ; etiology ; Humans ; Levofloxacin ; Male ; Meningitis ; etiology ; microbiology ; prevention & control ; Metronidazole ; administration & dosage ; Ofloxacin ; administration & dosage ; Prostatic Neoplasms ; pathology ; Ultrasound, High-Intensity Focused, Transrectal

Adult ; Carcinoma, Hepatocellular ; epidemiology ; pathology ; virology ; DNA, Viral ; blood ; genetics ; Female ; Genotype ; Hepatitis B ; epidemiology ; virology ; Hepatitis B Surface Antigens ; blood ; Hepatitis B virus ; genetics ; Humans ; Liver Neoplasms ; epidemiology ; pathology ; virology ; Male ; Middle Aged ; Neoplasm Staging ; Polymerase Chain Reaction ; methods

OBJECTIVETo evaluated the impact of baseline ABL kinase domain point mutations on responses to nilotinib in imatinib-resistant or-intolerant patients with chronic myeloid leukemia (CML).

METHODS34 CML patients after imatinib failure or intolerance received oral administration of 400 mg nilotinib twice daily. The median follow-up duration of nilotinib therapy was 14 (1.5-50) months. ABL kinase domain point mutations were detected from bone marrow of CML patients at baseline and once every 6 months before and after nilotinib therapy. Hematologic, cytogenetic, molecular response and progression were evaluated respectively at the same time.

RESULTSAmong 34 patients, 13 were in chronic phase (CP), 11 were in accelerated phase (AP), 10 were in blastic crisis (BC). Major cytogenetic response (MCyR) was achieved in 70% of patients with CP, 30% of patients with AP and BC (P = 0.027). Complete cytogenetic response (CCyR) was achieved in 70% of patients with CP and 20% of patients with AP and BP, respectively (P = 0.005). The 4-year progressive free survival of patients with CP and AP was (81.8 +/- 11.6)% and (20.5 +/- 12.9)%, respectively (P < 0.01). The cases of ABL kinase domain point mutations at baseline was 17 (50%). CHR was achieved in 56%, MCyR in 43%, CCyR in 37%, MMR in 31% of patients with baseline mutations versus 59% (P > 0.05), 53% (P > 0.05), 41% (P > 0.05), 18% (P > 0.05), respectively, of patients without baseline mutations. The CHR, MCyR, CCyR and MMR in patients who harbored mutations with high sensitivity to nilotinib in vitro (IC50 < or = 150 nmol/L) or mutations with unknown nilotinib sensitivity in vitro were equivalent to those responses in patients without mutations. Patients with mutations less sensitive to nilotinib in vitro (IC50 > 150 nmol/L, Y253H, F359V/C, T315I) achieved 17% of CHR and MCyR, none of them (6 cases) achieved CCyR, and 6 cases had disease progression within 24 mouth after treatment.

CONCLUSIONSNilotinib is a more effective option for imatinib-resistant or-intolerant CML patients. Response for patients with CP was better than patients with AP and BC. Mutational status at baseline may influence response. Less sensitive mutations may be associated with less favorable responses to nilotinib.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Benzamides ; Female ; Fusion Proteins, bcr-abl ; genetics ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; drug therapy ; genetics ; Male ; Middle Aged ; Piperazines ; pharmacology ; therapeutic use ; Point Mutation ; Protein-Tyrosine Kinases ; genetics ; Pyrimidines ; pharmacology ; therapeutic use ; Treatment Outcome ; Young Adult

OBJECTIVETo evaluate the factors for the conversion of transurethral resection of the prostate (TURP) to open prostatectomy and to provide clinical evidence for surgical options.

METHODSFrom January 1997 to March 2005, we performed 1 086 TURP and made retrospective analyses of 11 risk factors concerning the demographics, clinical history, laboratory data, ultrasound results, and intraoperative complications of the patients. In addition, multivariate logistic regression was used to determine those variables predicting the conversion of TURP.

RESULTSThirty-nine (3.59%) of the TURP cases required conversion, mostly because of uncontrollable hemorrhage (71.79%). Multivariate analyses showed that a prostate volume > 85.2 ml (OR = 2.568, P < 0.01), intraoperative slit of capsula prostatic (OR = 1.916, P < 0.01) and a second midstream bladder specimen (VB2) white blood cell count of the urine > 13.5/HP (OR = 1.486, P < 0.01) predicted the conversion to open prostatectomy.

CONCLUSIONBenign prostatic hyperplasia (BPH) patients with a huge prostate and those with intraoperative slit of capsula prostatic undergoing TURP are more likely to be converted. And uncontrollable hemorrhage, huge prostate and poor endoscopic vision are the major reasons for the conversion.

Aged ; Aged, 80 and over ; Humans ; Logistic Models ; Male ; Middle Aged ; Multivariate Analysis ; Postoperative Hemorrhage ; etiology ; Prostatectomy ; methods ; Prostatic Hyperplasia ; surgery ; Retrospective Studies ; Risk Factors ; Transurethral Resection of Prostate ; adverse effects ; methods ; Treatment Outcome

UNLABELLEDTo study the androgen dependence of the neurotransmitter, calcitonin gene-related peptide (CGRP) in rat penis.

METHODSForty-four Sprague-Dawley rats were randomly divided into Group A (intact controls), Group B (castrated) and Group C (gavaged with finasteride 4.5 mg.kg(-1).day(-1)). Four and ten weeks later respectively, half of rats in each group were anaesthetized. Blood samples were taken for the measurement of serum testosterone and dihydrotestosterone (DHT) by means of radioimmunoassay. Penile samples were harvested for the investigation of calcitonin gene related peptide (CGRP)-immunoreactive nerve fibers with immunohistochemistry. The computer-assisted imaging analysis system was applied to calculate the area proportion of the CGRP-positive nerve fibers (CGRP-PNF) in each group.

RESULTS1) Both 4 and 10 weeks later, testosterone and DHT levels in Group B decreased significantly compared with those in Group A, (P <0.05, P <0.01, respectively); DHT level in Group C was also significantly decreased in comparison with that in Group A for both 4- and 10- week animals (P <0.05); 2) There was no significant differences in area proportion of CGRP-PNF among Groups A, B and C 4 weeks after treatments (P >0.05); However, 10 weeks later, the proportion of CGRP-PNF in Groups B and C was significantly less than that in Group A (P <0.01); 3) The proportion of CGRP-PNF of 4-week animals in Groups B and C was significantly higher than that of 10-week animals (P <0.05).

CONCLUSIONThe expression of neurotransmitter, CGRP may depend on androgens, including testosterone and DHT in rat penis.

Androgens ; metabolism ; Animals ; Calcitonin Gene-Related Peptide ; metabolism ; Dihydrotestosterone ; blood ; Gene Expression Regulation ; Immunohistochemistry ; Male ; Penis ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Testosterone ; blood

AIMTo clarify the ultrastructural changes of penile tunica albuginea (TA) in streptozotocin (STZ)-induced diabetic rats.

METHODSIntraperitoneal injection of STZ was used to induce diabetes mellitus (DM) in 12 Sprague Dawley rats. Ten rats (age and weight-matched) were used as control. Blood samples from the tail snips of the rats were used for the determination of serum glucose levels with SureStep Plus Blood Meter. At week 4 and 10 after the injection, half of the rats in each group were sacrificed and penile samples were obtained from the middle third of the penile shaft for the examination of TA under scanning electron microscopy.

RESULTSIn the diabetic group, the serum glucose levels were higher (P<0.01 at both time points) and the TA were thinner (P<0.05) than those of the controls. In the control group, the fibers of TA were rich and arranged regularly and undulated, while in the diabetic group, the fibers were diminished, lost the undulations and were arranged irregularly.

CONCLUSIONIn rats, DM appeared to impair the penile TA ultrastructures and this impairment could contribute to diabetic erectile dysfunction in part by impairing the veno-occlusive function.

Animals ; Blood Glucose ; metabolism ; Diabetes Mellitus, Experimental ; pathology ; Male ; Microscopy, Electron, Scanning ; Penis ; pathology ; ultrastructure ; Rats ; Rats, Sprague-Dawley

This study was aimed to verify the efficacy of home-made LSI bcr/abl ES probe for detection of bcr/abl fusion gene and derivative chromosome 9 deletions in chronic myeloid leukemia (CML). Fluorescence in situ hybridization (FISH) was carried out with dual color bcr/abl extra signal (ES) probe in 97 cases of CML based on morphology and cytogenetic karyotype and 129 cases of non-hematological malignancies/non-myeloproliferative diseases with normal cytogenetic karyotype. For the patients with signals of 1R1G1F indicating der(9) deletions, FISH were done using ASS DNA probe. The results showed that 91 cases with standard t(9;22) and 6 cases with variant translocation of t(9;22) were detected by conventional G banding technique. All of the 97 patients displayed bcr/abl fusion gene by ES-FISH, including 16 cases with signal patterns of 1R1G1F showing der(9) deletions. Among the 16 cases with der(9) deletions, 13 cases were detected to have deletions of ASS gene. Meanwhile, none of the 129 cases of negative control showed bcr/abl fusion gene by ES-FISH. It is concluded that home-made LSI bcr/abl ES probe is effective to identify the bcr/abl fusion gene and der(9) deletions in CML, and the ES-FISH results are consistent with conventional cytogenetic karyotype.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; Chromosome Aberrations ; Chromosomes, Human, Pair 9 ; DNA Probes ; genetics ; Female ; Fusion Proteins, bcr-abl ; analysis ; genetics ; Gene Deletion ; Humans ; In Situ Hybridization, Fluorescence ; methods ; Karyotyping ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; diagnosis ; genetics ; Male ; Middle Aged ; Sequence Deletion ; Young Adult