Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 27
Filter
1.
Transl Androl Urol ; 10(8): 3423-3431, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34532267

ABSTRACT

BACKGROUND: Benign prostatic hyperplasia (BPH) is a common micturition disorder in middle-aged and elderly males, and it is one of the most common urology-related diseases worldwide. However, standard therapeutic drugs (α1-receptor blockers + 5α reductase inhibitors) do not provide anti-inflammatory or anti-infective effects. The Phellodendron Bawei tablet is a proprietary Chinese medicine with anti-inflammatory and anti-infective effects. Here, we analyzed whether the combination of standard therapeutic drugs and Phellodendron Bawei tablets has more advantages than placebo with standard management in improving the lower urinary tract symptoms (LUTs), sleep quality, sexual function, and medication compliance in patients with BPH. METHODS: This study was a prospective, double-blind, single-center, 6-month clinical trial in patients with BPH. Male patients, 45-75 years old, a history of moderate-to-severe BPH/LUTs for more than 6 months, moderate-to-severe LUTs [International Prostate Symptom Score (IPSS) ≥8], maximum urine flow rate (Qmax) of <15 mL/s, and prostate volume (PV) of >30 mL. All patients were randomly divided into two cohorts at baseline. The standard management (SM) group was treated with tamsulosin + finasteride + placebo, while the experimental group was treated with tamsulosin + finasteride + Phellodendron Bawei tablets. The clinical indicators were as follows: Age, body mass index (BMI), blood prostate-specific antigen (PSA), PV, Qmax, IPSS; IPSS voiding subscore (IPSS-V), IPSS storage subscore (IPSS-S), and IPSS quality of life (IPSS-QOL)], five-item version of the International Index of Erectile Function (IEFF-5) score, Athens Insomnia Scale (AIS) score, and the Medication Adherence Questionnaire (MAQ). And adverse drug reactions were observed. Student's t-test was used to analyze results. RESULTS: We randomly divided 120 patients into two groups, with 60 patients in each group, and a total of 105 patients completed the study. IPSS-S (P=0.027) and AIS scores (P<0.001) improved more significantly in the Phellodendron Bawei tablets + SM group, and the MAQ score in this group was lower (P=0.003). CONCLUSIONS: Phellodendron Bawei tablets combined with α1-receptor blockers and 5α-reductase inhibitors can improve lower urinary tract symptoms associated with urine storage, sleep quality, and medication compliance in patients with benign prostatic hyperplasia compared to placebo with standard management. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100046463.

2.
Ann Transl Med ; 9(15): 1246, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34532383

ABSTRACT

BACKGROUND: Benign prostatic hyperplasia (BPH) is a common urological condition in aging men. While dihydroartemisinin (DHA) exhibits a wide range of pharmacological activities, to date, there have been no studies examining the effects of DHA on BPH. METHODS: An in vivo BPH model was constructed in rats via daily subcutaneous injection of testosterone propionate (TP) for 28 consecutive days. Rats were randomly distributed into four groups and treated as follows: (I) control; (II) TP treatment; (III) TP and finasteride treatment (positive control); and (IV) TP and DHA treatment. At the end of the experiment, rats were sacrificed and the prostate weight, prostate index, thickness of the epithelium, collagen deposition, serum dihydrotestosterone (DHT) levels, 5α-reductase 2 (5AR-2) expression, and proliferating cell nuclear antigen (PCNA) levels in the prostate were examined. Normal human prostatic epithelial RWPE-1 cells were used in in vitro experiments to further investigate the anti-proliferative effects of DHA. RESULTS: TP increased the prostate weight and prostate index in rats, and this effect was reduced with DHA treatment. In addition, DHA attenuated the morphological changes and collagen deposition in the prostate tissue induced by TP. Furthermore, DHA reduced the expression of PCNA, serum DHT, and prostatic 5AR-2 in rats with TP-induced BPH. In vitro analysis revealed that DHA significantly inhibited the proliferation of TP-treated RWPE-1 cells. CONCLUSIONS: DHA significantly inhibited the development of BPH by suppressing serum DHT levels, prostatic 5AR-2 expression, and the proliferation of benign prostatic epithelial cells. Thus, DHA is a novel medicinal agent with potential therapeutic efficacy in the treatment of patients with BPH.

3.
Nanomaterials (Basel) ; 10(4)2020 Apr 24.
Article in English | MEDLINE | ID: mdl-32344620

ABSTRACT

First-principles calculations were performed to investigate the effects of boron/nitrogen dopant on the geometry, electronic structure and magnetic properties of the penta-graphene system. It was found that the electronic band gap of penta-graphene could be tuned and varied between 1.88 and 2.12 eV depending on the type and location of the substitution. Moreover, the introduction of dopant could cause spin polarization and lead to the emergence of local magnetic moments. The main origin of the magnetic moment was analyzed and discussed by the examination of the spin-polarized charge density. Furthermore, the direction of charge transfer between the dopant and host atoms could be attributed to the competition between the charge polarization and the atomic electronegativity. Two charge-transfer mechanisms worked together to determine which atoms obtained electrons. These results provide the possibility of modifying penta-graphene by doping, making it suitable for future applications in the field of optoelectronic and magnetic devices.

4.
J Laparoendosc Adv Surg Tech A ; 27(6): 623-628, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28051910

ABSTRACT

OBJECTIVE: To describe a newly developed transperitoneal intravesical technique for laparoscopic ureteral reimplantation in patients with terminal ureteral stenosis. METHODS: Between July 2009 and May 2015, laparoscopic transperitoneal intravesical ureteral reimplantation was performed in 16 patients with terminal ureteral stenosis without vesicoureteral reflux (VUR). An incision was made in the superior bladder wall of the affected side with an electric hook. The bladder mucosa was then circumferentially cut away from the ureteral orifice to a distance of 0.5 cm, and the intramural portion of the ureter was freed from the bladder wall and dissected until 4 to 5 cm of terminal ureter was mobilized. The stenotic segment was resected, and a longitudinal cut was made in the mobilized ureter. The terminal ureter was then evaginated and sutured to the bladder wall to form a papilla. All patients underwent standard postoperative examinations. RESULTS: All of the 16 operations were successful, and none required conversion to an extravesical approach or open surgery. The operation time ranged from 85 to 135 minutes (mean 98 minutes), and the estimated blood loss was ∼30-60 mL (mean 42 mL). There were no obvious intraoperative or postoperative complications. Resolution of hydronephrosis was achieved in all 16 patients, and VUR of the operated ureter was not detected at postoperative follow-up. CONCLUSIONS: The transperitoneal intravesical technique of laparoscopic ureteral reimplantation that we describe was safe and feasible in our 16 patients and may be an alternative surgical treatment for terminal ureteral stenosis in patients without VUR.


Subject(s)
Peritoneum/surgery , Ureter/surgery , Ureteral Obstruction/surgery , Adolescent , Adult , Constriction, Pathologic/surgery , Female , Humans , Laparoscopy/methods , Male , Middle Aged , Postoperative Complications/etiology , Replantation/methods , Treatment Outcome , Urologic Surgical Procedures/methods , Vesico-Ureteral Reflux/surgery , Young Adult
5.
Leuk Res ; 39(4): 424-8, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25721158

ABSTRACT

OBJECTIVE: The open-label, prospective, observational study aimed to evaluate whether decitabine (DAC) plus thalidomide versus DAC monotherapy improved progression-free (PFS), overall survival (OS) and acute myeloid leukemia-free survival (AML-FS) for risk-tailored elderly patients with myelodysplastic syndromes (MDS). METHOD: Enrolled 107 patients (age: 65-82 years) received DAC (52/107) or DAC plus thalidomide (55/107) therapy for MDS. RESULTS: 35/52 patients (67.3%) with DAC therapy reached overall response (OR), compared with 36/55 patients (65.5%) in DAC+thalidomide regimen (P>0.05). DAC+thalidomide administered did not gain more profits of PFS and OS than DAC monotherapy. Risk-tailored analysis showed that DAC+thalidomide therapy did not enhance PFS (48.9% versus 42.8%, P>0.05) and OS (78.6% versus 71.2%, P>0.05) when compared with simple DAC regimen. Nevertheless, DAC+thalidomide markedly improved OS over DAC monotherapy (50.6% versus 40.2%, P<0.05) in high risk profile. Meanwhile, low risk group was superior to high risk group in AML-FS (57.2% versus 21.3%, P<0.01), but DAC+thalidomide still did not prolong 2-year AML-FS when compared with DAC (32.4% versus 27.8%, P<0.05). Moreover, thalidomide had a favorable toxicity profile as a single agent. In comparison with DAC monotherapy, the DAC+thalidomide regimen was relatively well tolerated. There was no severe non-hematological toxicity appearing in elderly patients with MDS. CONCLUSIONS: The study demonstrated that DAC+thalidomide improved 2-year OS for high risk patients. Thalidomide's proven activity and low toxicity profile made it an alternative treatment option for risk-tailored elderly patients with MDS.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Myelodysplastic Syndromes/drug therapy , Myelodysplastic Syndromes/mortality , Aged , Aged, 80 and over , Azacitidine/administration & dosage , Azacitidine/analogs & derivatives , Decitabine , Female , Follow-Up Studies , Humans , Male , Middle Aged , Myelodysplastic Syndromes/pathology , Neoplasm Staging , Prognosis , Prospective Studies , Risk Factors , Survival Rate , Thalidomide/administration & dosage
6.
Med Oncol ; 31(10): 233, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25213763

ABSTRACT

This open-label, prospective, observational study aimed to evaluate disease-free survival (DFS), overall survival (OS), PML-RARα polymerase chain reaction (PCR) monitoring and safety in elderly patients with de novo acute promyelocytic leukemia (APL) who were treated with either arsenic trioxide (As2O3) or medium-dose cytosine arabinoside (MiDAC) as frontline consolidation regimens. A total of 167 patients (age≥65 years old) received all-trans retinoic acid + daunorubicin as induction therapy. Of these patients, 22 died before attaining complete remission; the remaining 145 subjects received MiDAC- or As2O3-based consolidation therapy. As2O3 was superior to MiDAC for improving DFS and OS. This benefit appeared to result from the longer 5-year DFS (92.0 vs. 69.1%, P<0.01) and OS (94.5 vs. 79.7%, P<0.05) of As2O3 compared to MiDAC. PCR monitoring demonstrated that As2O3 promoted a lower positive rate than MiDAC (21.7 vs. 4.5%, P<0.05), but this treatment had no advantage for maintaining a low positive rate in the high-risk group. The most common life-threatening adverse drug effects in patients with MiDAC were platelet counts<25×10(9)/L (85.7%), leukocyte counts<1.0×10(9)/L (81.4%) and severe infection (84.3%). In contrast, the As2O3 regimen rarely caused leukocyte counts<1.0×10(9)/L (22.7%, P<0.01), platelet counts<25×10(9)/L (37.3%, P<0.01) or severe infection (21.3%, P<0.01). These data confirm that MiDAC should not be added during the initial consolidation of patients with APL because this treatment is far less effective, particularly in patients with a low-risk profile, and far more toxic than As2O3.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Leukemia, Promyelocytic, Acute/drug therapy , Aged , Aged, 80 and over , Arsenic Trioxide , Arsenicals/administration & dosage , Cytarabine/administration & dosage , Daunorubicin/administration & dosage , Disease-Free Survival , Female , Humans , Leukemia, Promyelocytic, Acute/mortality , Leukemia, Promyelocytic, Acute/pathology , Male , Oxides/administration & dosage , Polymerase Chain Reaction , Prospective Studies , Survival Rate , Tretinoin/administration & dosage
7.
Leuk Res ; 38(10): 1177-83, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25069759

ABSTRACT

OBJECTIVE: This open-label, prospective, observational study aimed to evaluate treatment response, efficacy therapy and safety to IFN α-2b for the essential thrombocythemia (ET) and polycythemia vera (PV) with JAK2V617F positive mutation. METHOD: A total of 123 ET patients received IFNα-2b therapy with JAK2V617F positive or negative mutation; and 136 PV patients with JAK2V617F(+) received IFNα-2b or hydroxyurea (HU) therapy according to random number assignment (ages 18-65 years old). RESULT: ET patients receiving IFN α-2b with JAK2V617F(+) had a greater advantage in overall hematologic response (OHR) than JAK2V617F(-) (83.3% versus 61.4%, P<0.01). For PV patients with JAK2V617F(+), IFN had no OHR superiority to HU (70.3% versus 70.8%, P>0.05), but which gained a greater satisfactory molecular response than HU (54.7% versus 19.4%, P<0.01). IFN significantly decreased the phlebotomy rate, which was better than HU for MPDs patients with OHR than HU (3.6% versus 65.7%, P<0.01). Furthermore, ET patients with JAK2V617F(+) demonstrated a definite advantage over JAK2V617F(-) in five-year PFS (75.9% versus 47.6%, P<0.05). For PV patients with JAK2V617F(+), IFN α-2b was superior to HU in five-year PFS (66.3% versus 46.7%, P<0.01). Moreover, IFN α-2b also contributed to improved vasomotor symptoms in MPDs, and especially significantly decreased the incidence of distal paresthesias (14.1% versus 37.5%) and erythromelalgia (9.4% versus 29.2%) better than HU (P<0.01). Meanwhile, IFN did not observe the severe hematological adverse events in patients with PV or ET. CONCLUSION: The data confirmed that IFN α-2b benefited the patients with ET or PV, particularly for JAK2V617F(+) mutation.


Subject(s)
Interferon-alpha/therapeutic use , Janus Kinase 2/genetics , Polycythemia Vera/drug therapy , Thrombocythemia, Essential/drug therapy , Adult , Aged , Female , Humans , Hydroxyurea , Interferon alpha-2 , Kaplan-Meier Estimate , Male , Middle Aged , Mutation , Polycythemia Vera/genetics , Polycythemia Vera/mortality , Recombinant Proteins/therapeutic use , Thrombocythemia, Essential/genetics , Thrombocythemia, Essential/mortality
8.
Med Oncol ; 31(8): 104, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24985882

ABSTRACT

The open-label, prospective, observational study aimed to evaluate whether the addition of maintenance rituximab (MR) improved progression-free survival (PFS) and overall survival (OS), after fludarabine, cyclophosphamide, and rituximab (FCR) for cytogenetic risk-tailored elderly patients with chronic lymphocytic leukemia (CLL). Enrolled 201 patients (ages 65-84 years) who received FCR and gained an overall response. One hundred and four of 201 patients were in the observation (OBS) arm while 97/201 patients continued to receive MR therapy. After FCR, no more benefits were provided by MR versus OBS in cytogenetic better intermediate-risk cohort. PFS at 10 years reached 68.6 versus 58.1 % (P > 0.05). Ten-year OS was 81.8 versus 74.6 % (P > 0.05). However, the improvement of PFS and OS were as dramatic as the improvements of being MR treating versus OBS mainly in the poor-risk cohort. PFS at 10 years reached 57.1 versus 22.7 % (P < 0.01), and 10-year OS was 71.2 versus 41.7 % (P < 0.01). Compared with OBS, no severe hematologic adverse events (AEs) (Grades 3-4) appeared in patients with MR; only some mild non-hematologic AEs incurred (nausea-vomiting 0.96 %, allergy 1.9 % and infection 1.9 %) during the maintenance treatment. The study showed that MR improved 10-year RFS and OS for cytogenetic poor-risk patients with CLL.


Subject(s)
Antibodies, Monoclonal, Murine-Derived/adverse effects , Antibodies, Monoclonal, Murine-Derived/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Aged , Aged, 80 and over , Antibodies, Monoclonal, Murine-Derived/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cyclophosphamide/administration & dosage , Disease-Free Survival , Female , Follow-Up Studies , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/mortality , Male , Prospective Studies , Risk Factors , Rituximab , Treatment Outcome , Vidarabine/administration & dosage , Vidarabine/analogs & derivatives
9.
Med Oncol ; 31(5): 962, 2014 May.
Article in English | MEDLINE | ID: mdl-24743870

ABSTRACT

The open-label, prospective study aimed to evaluate the efficacy and safety for standard intensive chemotherapy compared with attenuated therapy in elderly patients with acute myeloid leukemia (AML). A total of 297 patients between 65 and 82 years were enrolled in the study. The 141 patients received standard-dose therapy (daunorubicin 45 mg/m(2) × 3 days with cytarabine 100 mg/m(2) × 7 days for induction therapy, while post-induction therapy consisted of high-dose cytarabine 1.5 g/m(2) × 4 days), and the attenuated treatment (daunorubicin 30 mg/m(2) × 3 days with cytarabine 75 mg/m(2) × 7 days for induction therapy, while post-induction therapy consisted of attenuated high-dose Ara-C 1.0 g/m(2) × 3 days) was administered to the remaining 156 patients, based on a random number assigned. Total 168 patients (56.6%) achieved complete remission with an incomplete blood recovery (CR)/CRi. No significant differences were observed between the two treatments (P = 0.60). Attenuated chemotherapy improved overall survival (OS) and progression-free survival (PFS) compared to standard-dose therapy; 5-year OS values for these two groups were 39 and 24 months, respectively (P < 0.001), and the PFS values for these two groups were 35 versus 23 months (P < 0.001). In addition, the attenuated treatment with a poor risk profile overcame the negative impact and yielded OS and PFS values similar to those of the standard-dose chemotherapy with a better-to-intermediate risk profile. Five-year OS values for these two groups were 28 versus 28 months (P = 0.89), and the 5-year PFS values were 27 and 28 months, respectively (P = 0.89). The most common adverse drug effect for chemotherapy was agranulocytosis (98.3%). There was a significant difference in early mortality between the attenuated and standard-dose treatment groups (0.64% vs. 7.1%, respectively, P < 0.01). Standard intensive chemotherapy is less effective and far more toxic than attenuated induction and post-induction regimen in elderly patients with AML.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Leukemia, Myeloid, Acute/drug therapy , Aged , Aged, 80 and over , Cytarabine/administration & dosage , Daunorubicin/administration & dosage , Female , Follow-Up Studies , Humans , Leukemia, Myeloid, Acute/mortality , Leukemia, Myeloid, Acute/pathology , Male , Neoplasm Staging , Prognosis , Prospective Studies , Remission Induction , Survival Rate
10.
J Cancer Res Clin Oncol ; 140(2): 303-9, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24337419

ABSTRACT

BACKGROUND: This was an open-label, observational, prospective assessment. We conducted an analysis of the impact of bortezomib-based therapy (PAD: bortezomib, doxorubicin, high-dose dexamethasone vs. CBd: cyclophosphamide bortezomib, low-dose dexamethasone) on the survival rates and adverse events in elderly patients with newly diagnosed multiple myeloma (MM). METHODS: Out of 303 patients, 128 received the PAD regimen and the other 175 patients received the CBd induction therapy (age 65-89 years). Baseline patient characteristics between the two cohorts were balanced in age (P = 0.69), international staging system (ISS) prognostic stages (P = 0.90), serum calcium (P = 0.70), and serum creatinine (P = 0.52). RESULTS: Overall response (OS) after the induction chemotherapy was achieved in 214 of 303 patients (70.6 %), with no significant differences observed between the two treatment groups (71.9 vs. 69.7 %, P = 0.68). Patients with ISS stage 2 reached the same 5-year OS advantages compared to patients with ISS stage 1, because they received bortezomib-based PAD or CBd treatments. Patients receiving CBd protocol gained similar satisfactory progression-free survival (PFS) results when compared to the PAD regimen group: PFS at 5 years reached 58.2 versus 58.9 % (P = 0.85). Five-year OS in the CBd arm had significant advantages compared to the PAD group, 79.9 versus 49.9 % (P < 0.05). The overall safety profiles showed that 26 of 128 (20.3 %) patients died in the PAD arm, while 13 of 175 patients died (7.4 %) in the CBd group (P < 0.01). Similarly, the PAD arm had a higher serious infection rate than that of the CBd arm (39.2 vs. 13.1 %, P < 0.01). CONCLUSIONS: Bortezomib benefits elderly patients with newly diagnosed MM; they achieve satisfactory treatment responses and survival advantages. Further, patients treated with CBd have superior treatment advantages, with a predictable safety profile, when compared to the PAD regimen.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Multiple Myeloma/drug therapy , Aged , Aged, 80 and over , Boronic Acids/administration & dosage , Bortezomib , Cyclophosphamide/administration & dosage , Dexamethasone/administration & dosage , Doxorubicin/administration & dosage , Female , Follow-Up Studies , Humans , Male , Multiple Myeloma/mortality , Multiple Myeloma/pathology , Neoplasm Staging , Prognosis , Prospective Studies , Pyrazines/administration & dosage , Survival Rate
11.
Can J Gastroenterol ; 27(8): 467-75, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23936877

ABSTRACT

BACKGROUND AND OBJECTIVES: The diagnostic value of stool DNA (sDNA) testing for colorectal neoplasms remains controversial. To compensate for the lack of large-scale unbiased population studies, a meta-analysis was performed to evaluate the diagnostic value of sDNA testing for multiple markers of colorectal cancer (CRC) and advanced adenoma. METHODS: The PubMed, Science Direct, Biosis Review, Cochrane Library and Embase databases were systematically searched in January 2012 without time restriction. Meta-analysis was performed using a random-effects model using sensitivity, specificity, diagnostic OR (DOR), summary ROC curves, area under the curve (AUC), and 95% CIs as effect measures. Heterogeneity was measured using the χ(2) test and Q statistic; subgroup analysis was also conducted. RESULTS: A total of 20 studies comprising 5876 individuals were eligible. There was no heterogeneity for CRC, but adenoma and advanced adenoma harboured considerable heterogeneity influenced by risk classification and various detection markers. Stratification analysis according to risk classification showed that multiple markers had a high DOR for the high-risk subgroups of both CRC (sensitivity 0.759 [95% CI 0.711 to 0.804]; specificity 0.883 [95% CI 0.846 to 0.913]; AUC 0.906) and advanced adenoma (sensitivity 0.683 [95% CI 0.584 to 0.771]; specificity 0.918 [95% CI 0.866 to 0.954]; AUC 0.946) but not for the average-risk subgroups of either. In the methylation subgroup, sDNA testing had significantly higher DOR for CRC (sensitivity 0.753 [95% CI 0.685 to 0.812]; specificity 0.913 [95% CI 0.860 to 0.950]; AUC 0.918) and advanced adenoma (sensitivity 0.623 [95% CI 0.527 to 0.712]; specificity 0.926 [95% CI 0.882 to 0.958]; AUC 0.910) compared with the mutation subgroup. There was no significant heterogeneity among studies for subgroup analysis. CONCLUSION: sDNA testing for multiple markers had strong diagnostic significance for CRC and advanced adenoma in high-risk subjects. Methylation makers had more diagnostic value than mutation markers.


Subject(s)
Adenoma/diagnosis , Biomarkers, Tumor/analysis , Colonic Neoplasms/diagnosis , DNA/analysis , Feces/chemistry , Rectal Neoplasms/diagnosis , Area Under Curve , DNA Methylation/genetics , Humans , Mutation/genetics , ROC Curve , Risk Assessment , Sensitivity and Specificity
12.
Clin Colorectal Cancer ; 11(4): 280-90, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22609129

ABSTRACT

BACKGROUND: Stool-based DNA testing for colorectal cancer is becoming a favored alternative to existing DNA screening tests. However, current methods of analysis often become more complicated and costly with increased sensitivity. The high-resolution melting assay (HRMA) is a simple and rapid mutation scanning method with low cost and superb accuracy. In this study, we verified the accuracy of HRMA for screening KRAS/TP53 mutations in stool-isolated DNA from patients with colorectal cancer. MATERIALS AND METHODS: Comparing to direct DNA sequencing, the accuracy of HRMA was verified by detecting KRAS/TP53 mutations in 2 independent stages. In study stage I, both tissue and stool samples from colorectal neoplasm patients were analyzed. In study stage II, stool samples from patients with colorectal neoplasms, and normal controls in clinical screening settings were examined. RESULTS: In study stage I, the HRMA identified 14 of 17 target mutations (82.4%) in stools from cancer patients, and 4 of 5 (80.0%) target mutations in stools from advanced adenoma patients. The mutation detection rate in fecal samples (45.0%; 18/40) and referred tissue samples (55.0%; 22/40) was highly consistent (κ = 0.79). The HRMA detected 1% mutant DNA in a background of wild type DNA. In study stage II, the HRMA assay detected 58.8% (20/34) mutations in tumor samples, 41.5% (17/41) in advanced adenomas samples, and 3.33% (2/60) in age-matched normal control samples. The results from HRMA and DNA sequencing revealed 100% sensitivity and specificity in both tissue and stool samples. CONCLUSION: HRMA is a simple, reliable, and sensitive method for detecting DNA mutations in the stool samples from patients with colorectal neoplasms.


Subject(s)
Adenocarcinoma, Mucinous/diagnosis , Adenocarcinoma/diagnosis , Colorectal Neoplasms/diagnosis , DNA/genetics , Feces/chemistry , Mutation/genetics , Transition Temperature , Adenocarcinoma/genetics , Adenocarcinoma, Mucinous/genetics , Adult , Aged , Aged, 80 and over , Case-Control Studies , Colorectal Neoplasms/genetics , Female , Follow-Up Studies , Humans , Male , Mass Screening , Middle Aged , Neoplasm Grading , Neoplasm Staging , Polymerase Chain Reaction , Prognosis , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins p21(ras) , Sensitivity and Specificity , Tumor Suppressor Protein p53/genetics , ras Proteins/genetics
13.
J Cancer Res Clin Oncol ; 138(1): 125-32, 2012 Jan.
Article in English | MEDLINE | ID: mdl-22057732

ABSTRACT

BACKGROUND: In international prognostic index (IPI) risk-tailored adult patients with diffuse large B-cell lymphoma (DLBCL), it is still unclear whether the addition of maintenance rituximab (MR) improves progression-free (PFS) and overall survival (OS), after RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) therapy. METHODS: In our study, 207 patients (age: 21-59 years) received six 14-day cycles of RCHOP and gained overall response. After RCHOP, 98 patients were enrolled in the observation (OBS) arm. 109 patients continued to receive MR therapy. RESULTS: In IPI risk <2 profile, PFS at 5 years reached 72.9% (MR arm) versus 56% (OBS arm) (P = 0.033). In IPI risk ≥2 profile, PFS estimation at 5 years was 44.9% (MR arm) versus 33.5% (OBS arm) (P = 0.006). It is noteworthy that patients with IPI ≥2 who received MR achieved PFS similar to that for patients in the OBS arm with the IPI <2, 44.9% versus 56% (P = 0.97). In patients with an IPI <2, OS at 5 years was 83.2% (MR arm) versus 81.2% (OBS arm) (P = 0.708). In patients with an IPI ≥2, 5-year OS estimation was 44.6% (MR arm) versus 40.5% (OBS arm) (P = 0.067). Subgroup analysis of patients with an IPI ≥3 risk profile shows a survival benefit for patients receiving MR. OS at 5 years was 62% (MR arm) versus 49% (OBS arm), (P = 0.033). CONCLUSIONS: In conclusion, maintenance rituximab after RCHOP improves progression-free survival. In addition, overall survival is improved for patients with an IPI ≥3 risk profile receiving MR.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, Large B-Cell, Diffuse/drug therapy , Adolescent , Adult , Antibodies, Monoclonal, Murine-Derived/administration & dosage , Cyclophosphamide/administration & dosage , Disease-Free Survival , Doxorubicin/administration & dosage , Drug Administration Schedule , Humans , Maintenance Chemotherapy , Middle Aged , Prednisone/administration & dosage , Rituximab , Vincristine/administration & dosage , Young Adult
14.
Med Oncol ; 29(3): 2088-94, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22038728

ABSTRACT

The purpose of the study was to evaluate event-free survival (EFS), overall survival (OS) and safety for early addition of arsenic trioxide (As(2)O(3)) as frontline consolidation therapy compared to high-dose arabinoside (HiDAC) in adult patients with de novo acute promyelocytic leukemia (APL). 271 patients (aged 17-65 years) received consolidation therapy containing As(2)O(3) (two 21-day courses) or HiDAC regimen. EFS at 5 years was 75% versus 54% (P < 0.001), and OS at 5 years was 83% versus 71% (P = 0.002) in As(2)O(3) and HiDAC treatment arms. 139 patients treated with As(2)O(3), EFS at 5 years reached 79% versus 56% (P = 0.014), but OS at 5 years was 77% versus 84% (P = 0.32) in low-risk (WBC ≤ 10 × 10(9)/L) and high-risk (WBC > 10 × 10(9)/L) cohorts. Further, patients treated with As(2)O(3) rarely incurred agranulocytosis (1.4%, P < 0.001), or severe infection (0.7%, P < 0.001). It is still very well tolerated compared to HiDAC. We confirmed that As(2)O(3) as a first-line consolidation regimen provided significant benefits of OS to patients with APL. The As(2)O(3) regimen made low-risk patients gain more EFS benefits than high-risk group. The high-risk cohort receiving As(2)O(3) overcame the negative impact, yielding OS similar to that for with the low-risk patients treated with As(2)O(3).


Subject(s)
Antineoplastic Agents/therapeutic use , Arsenicals/therapeutic use , Consolidation Chemotherapy/methods , Cytarabine/therapeutic use , Leukemia, Promyelocytic, Acute/drug therapy , Oxides/therapeutic use , Adolescent , Adult , Aged , Antineoplastic Agents/adverse effects , Antineoplastic Combined Chemotherapy Protocols , Arsenic Trioxide , Arsenicals/adverse effects , Cytarabine/administration & dosage , Cytarabine/adverse effects , Daunorubicin , Disease-Free Survival , Female , Humans , Kaplan-Meier Estimate , Leukemia, Promyelocytic, Acute/mortality , Male , Middle Aged , Oxides/adverse effects , Tretinoin/therapeutic use , Young Adult
15.
PLoS One ; 6(12): e28078, 2011.
Article in English | MEDLINE | ID: mdl-22194806

ABSTRACT

BACKGROUND: High Resolution Melting Analysis (HRMA) is becoming the preferred method for mutation detection. However, its accuracy in the individual clinical diagnostic setting is variable. To assess the diagnostic accuracy of HRMA for human mutations in comparison to DNA sequencing in different routine clinical settings, we have conducted a meta-analysis of published reports. METHODOLOGY/PRINCIPAL FINDINGS: Out of 195 publications obtained from the initial search criteria, thirty-four studies assessing the accuracy of HRMA were included in the meta-analysis. We found that HRMA was a highly sensitive test for detecting disease-associated mutations in humans. Overall, the summary sensitivity was 97.5% (95% confidence interval (CI): 96.8-98.5; I(2) = 27.0%). Subgroup analysis showed even higher sensitivity for non-HR-1 instruments (sensitivity 98.7% (95%CI: 97.7-99.3; I(2) = 0.0%)) and an eligible sample size subgroup (sensitivity 99.3% (95%CI: 98.1-99.8; I(2) = 0.0%)). HRMA specificity showed considerable heterogeneity between studies. Sensitivity of the techniques was influenced by sample size and instrument type but by not sample source or dye type. CONCLUSIONS/SIGNIFICANCE: These findings show that HRMA is a highly sensitive, simple and low-cost test to detect human disease-associated mutations, especially for samples with mutations of low incidence. The burden on DNA sequencing could be significantly reduced by the implementation of HRMA, but it should be recognized that its sensitivity varies according to the number of samples with/without mutations, and positive results require DNA sequencing for confirmation.


Subject(s)
DNA Mutational Analysis/methods , Disease/genetics , Mutation/genetics , Nucleic Acid Denaturation , Humans , Likelihood Functions , Multivariate Analysis , Odds Ratio , Regression Analysis
16.
Mol Biol Cell ; 21(20): 3601-14, 2010 Oct 15.
Article in English | MEDLINE | ID: mdl-20810788

ABSTRACT

Cyclin-dependent kinase 5 (Cdk5) plays a key role in the development of the mammalian nervous system; it phosphorylates a number of targeted proteins involved in neuronal migration during development to synaptic activity in the mature nervous system. Its role in the initial stages of neuronal commitment and differentiation of neural stem cells (NSCs), however, is poorly understood. In this study, we show that Cdk5 phosphorylation of p27(Kip1) at Thr187 is crucial to neural differentiation because 1) neurogenesis is specifically suppressed by transfection of p27(Kip1) siRNA into Cdk5(+/+) NSCs; 2) reduced neuronal differentiation in Cdk5(-/-) compared with Cdk5(+/+) NSCs; 3) Cdk5(+/+) NSCs, whose differentiation is inhibited by a nonphosphorylatable mutant, p27/Thr187A, are rescued by cotransfection of a phosphorylation-mimicking mutant, p27/Thr187D; and 4) transfection of mutant p27(Kip1) (p27/187A) into Cdk5(+/+) NSCs inhibits differentiation. These data suggest that Cdk5 regulates the neural differentiation of NSCs by phosphorylation of p27(Kip1) at theThr187 site. Additional experiments exploring the role of Ser10 phosphorylation by Cdk5 suggest that together with Thr187 phosphorylation, Ser10 phosphorylation by Cdk5 promotes neurite outgrowth as neurons differentiate. Cdk5 phosphorylation of p27(Kip1), a modular molecule, may regulate the progress of neuronal differentiation from cell cycle arrest through differentiation, neurite outgrowth, and migration.


Subject(s)
Cell Differentiation , Cyclin-Dependent Kinase 5/metabolism , Cyclin-Dependent Kinase Inhibitor p27/metabolism , Neural Stem Cells/cytology , Neural Stem Cells/enzymology , Phosphothreonine/metabolism , Amino Acid Sequence , Animals , Apoptosis , Cell Proliferation , Cyclin-Dependent Kinase 5/deficiency , Cyclin-Dependent Kinase Inhibitor p27/chemistry , Mice , Molecular Sequence Data , Mutation/genetics , Neurites/metabolism , Neurogenesis , Phosphorylation , Phosphoserine/metabolism , Protein Transport , RNA, Small Interfering/metabolism , Substrate Specificity , Transfection
17.
Neurosci Lett ; 412(3): 233-8, 2007 Feb 02.
Article in English | MEDLINE | ID: mdl-17178437

ABSTRACT

Cyclin-dependent kinase 5 (cdk5) is a ubiquitous protein activated by neuron-specific activators, p35 and p39. Cdk5 regulates neuronal migration, differentiation, axonogenesis, synaptic transmission and apoptosis. However, its role in primary neurogenesis remains unexplored. Here, we have cloned and characterized the zebrafish cdk5 ortholog. Zebrafish cdk5 is 96% identical to its human counterpart. In situ hybridization analyses demonstrated that zebrafish cdk5 transcripts are ubiquitously expressed as early as the blastula stage. At 11.5h of development, cdk5 transcripts were present in the neural plate at the domains where primary neurons begin to be specified. RT-PCR analyses showed equal levels of cdk5 transcripts up to 72 h of development. SiRNA-mediated cdk5 knockdown resulted in a reduction in primary sensory neurons of the trigeminal ganglia of the peripheral nervous system, suggesting that cdk5 plays a crucial role in the development of the peripheral nervous system.


Subject(s)
Cyclin-Dependent Kinase 5/genetics , Cyclin-Dependent Kinase 5/metabolism , Gene Expression Regulation, Developmental/physiology , Zebrafish/genetics , Animals , Cloning, Molecular , Embryonic Development/drug effects , Embryonic Development/physiology , Gene Expression Regulation, Developmental/drug effects , Humans , In Situ Hybridization/methods , Mice , RNA, Small Interfering/pharmacology
18.
Mol Biol Cell ; 18(2): 404-13, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17108320

ABSTRACT

Cdk5, a cyclin-dependent kinase, is critical for neuronal development, neuronal migration, cortical lamination, and survival. Its survival role is based, in part, on "cross-talk" interactions with apoptotic and survival signaling pathways. Previously, we showed that Cdk5 phosphorylation of mitogen-activated protein kinase kinase (MEK)1 inhibits transient activation induced by nerve growth factor (NGF) in PC12 cells. To further explore the nature of this inhibition, we studied the kinetics of NGF activation of extracellular signal-regulated kinase (Erk)1/2 in cortical neurons with or without roscovitine, an inhibitor of Cdk5. NGF alone induced an Erk1/2-transient activation that peaked in 15 min and declined rapidly to baseline. Roscovitine, alone or with NGF, reached peak Erk1/2 activation in 30 min that was sustained for 48 h. Moreover, the sustained Erk1/2 activation induced apoptosis in cortical neurons. Significantly, pharmacological application of the MEK1 inhibitor PD98095 to roscovitine-treated cortical neurons prevented apoptosis. These results were also confirmed by knocking down Cdk5 activity in cortical neurons with Cdk5 small interference RNA. Apoptosis was correlated with a significant shift of phosphorylated tau and neurofilaments from axons to neuronal cell bodies. These results suggest that survival of cortical neurons is also dependent on tight Cdk5 modulation of the mitogen-activated protein kinase signaling pathway.


Subject(s)
Apoptosis , Cyclin-Dependent Kinase 5/metabolism , Mitogen-Activated Protein Kinases/metabolism , Neurons/physiology , Animals , Cell Survival/drug effects , Cerebral Cortex/cytology , Cerebral Cortex/enzymology , Cyclin-Dependent Kinase 5/antagonists & inhibitors , Cyclin-Dependent Kinase 5/genetics , Cytoskeletal Proteins/metabolism , MAP Kinase Kinase 1/antagonists & inhibitors , MAP Kinase Kinase 1/metabolism , Mitogen-Activated Protein Kinase 1/antagonists & inhibitors , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/antagonists & inhibitors , Mitogen-Activated Protein Kinase 3/metabolism , Mitogen-Activated Protein Kinases/antagonists & inhibitors , Neurons/drug effects , Neurons/enzymology , PC12 Cells , Phosphorylation , Purines/pharmacology , RNA, Small Interfering/pharmacology , Rats , Roscovitine , Signal Transduction
19.
J Neurochem ; 99(1): 251-9, 2006 Oct.
Article in English | MEDLINE | ID: mdl-16911583

ABSTRACT

Cyclin-dependent kinase 5 (cdk5), a member of the cyclin-dependent kinase family, is expressed predominantly in post-mitotic cell populations. Unlike the other cdks, cdk5 is abundant and most active in differentiated neurons. Here, we describe the function of a cdk5 ortholog in zebrafish. Cdk5 catalytic activity is meager but present in early stages of development. However, at 24 h post-fertilization (hpf), the activity is remarkably higher and continues to be high through 48 and 72 hpf. Knocking down cdk5 by micro-injection of a specific siRNA resulted in decreased cdk5 protein level accompanied by reduced kinase activity. In the cdk5 siRNA-injected embryos, the number of primary sensory Rohon-Beard (RB) neurons was significantly reduced and there were more apoptotic cells in the brain. These phenotypes were rescued by co-injection of cdk5 mRNA. Within the first two days of development, RB neurons undergo apoptosis in zebrafish. To examine whether cdk5 has a role in RB neuron survival, cdk5 mRNA was injected into the one- to two-cell embryos. In these embryos, RB neuron apoptosis was inhibited compared with the uninjected control embryos. These results suggest that in zebrafish, cdk5 influences RB neuron survival and potentially regulates early neuronal development.


Subject(s)
Cyclin-Dependent Kinase 5/genetics , Cyclin-Dependent Kinase 5/metabolism , Neurons/cytology , Neurons/enzymology , Zebrafish Proteins/metabolism , Animals , Cell Death , Cell Survival , Embryo, Nonmammalian/cytology , Embryonic Development , Gene Expression Regulation, Developmental , Immunohistochemistry , RNA, Small Interfering/genetics , Zebrafish/embryology , Zebrafish Proteins/genetics
20.
Drug News Perspect ; 17(4): 258-66, 2004 May.
Article in English | MEDLINE | ID: mdl-15334175

ABSTRACT

Muscarinic acetylcholine receptors (mAChRs) belong to the G-protein-coupled receptor superfamily that transduces signals through multiple intracellular signaling cascades to regulate a wide variety of physiological responses. Recently, it has been discovered that subtypes of mAChRs are expressed in proliferative neuroepithelial cells of the ventricular zone and in basic fibroblast growth factor-expanded neural stem and progenitor cell cultures. Activation of the mAChRs by ACh or its analogue carbachol leads to increased DNA synthesis and neurogenesis. The mitogenic effects of muscarinic agonists are likely mediated via mAChR-activated multisignaling pathways. The exact intracellular mechanisms underlying mAChR-modulated DNA synthesis and neurogenesis are not fully understood. However, several pathways through Ras-mitogen-activated protein kinase, phosphatidylinositol 3-kinase-Akt, protein kinase C, c-Src and Ca(2+) signaling have been shown to play roles in this dynamic process. These novel signaling cascades may improve our understanding of the intracellular mechanisms underlying mAChR-stimulated neural progenitor proliferation and provide insights for therapeutic drug development.


Subject(s)
Neurons/physiology , Receptors, Muscarinic/drug effects , Signal Transduction/drug effects , Stem Cells/physiology , Animals , Cell Division/drug effects , Cell Division/physiology , Humans , MAP Kinase Signaling System/drug effects , Muscarinic Agonists/pharmacology , Neurons/drug effects , Phosphatidylinositol 3-Kinases/physiology , Protein Kinase C/physiology , Receptor Cross-Talk/drug effects , Receptor Cross-Talk/physiology , Receptors, Muscarinic/physiology , Stem Cells/drug effects
SELECTION OF CITATIONS
SEARCH DETAIL
...