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Objective:To investigate the accumulation of porphyrin metabolites [uroporphyrinogen (UP) Ⅰ and coproporphyrinogen (CP) Ⅲ] induced by 5-aminolevulinic acid (5-ALA) in the urine of rats with colorectal cancer.Methods:The rat model of colorectal cancer was established by dimethylhydrazine (DMH). Urine samples were collected from 30 colorectal cancer rats (colorectal cancer group) and 30 normal rats (normal group). Each animal was given 5-ALA (50 mg/kg) by gavage, and urine was collected after 2, 4, 6 and 8 h. The contents of urinary porphyromogen Ⅰ and porphyromogen faecalis Ⅲ in urine were detected by high performance liquid chromatography (HPLC).Results:There was no significant difference in the contents of UP Ⅰ and CP Ⅲ in urine between colorectal cancer group and normal group before oral administration of 5-ALA ( P>0.05). After oral administration of 5-ALA, the contents of UP Ⅰ and CP Ⅲ in urine of colorectal cancer group were significantly higher than those of normal group ( P<0.05). The contents of UP Ⅰ and CP Ⅲ in urine of colorectal cancer group reached the highest value at 4 hours. According to the receiver operating characteristic (ROC) curve drawn from 4-hour test results, the threshold value of UP Ⅰ for colorectal cancer diagnosis was 50.43 μmol/g, with corresponding sensitivity 96.7%, and the specificity 63.3%, respectively. The threshold value of CP Ⅲ for colorectal cancer diagnosis was 108.85 μmol/g, with corresponding sensitivity 66.7%, and the specificity 86.7%, respectively. Conclusions:The accumulation of porphyrin metabolites induced by 5-ALA in the urine of rats with colorectal cancer is significant. The porphyrin metabolites in urine may be a new tumor marker of colorectal cancer, which provides an experimental basis for the diagnosis of colorectal cancer.
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Objective:To explore the effect and mechanism of 5-Aminolevulinic Acid-Photodynamic Therapy (5-ALA-PDT) on the apoptosis of the human colonic carcinoma HT-29 cells.Methods:HT-29 cells were cultured in vivio and divided into four groups: blank control group, 5-ALA group, PDT group and 5-ALA-PDT group.The control group was not given photosensitizer and light treatment; 5-ALA group was given photosensitizer ; PDT group was given light treatment; 5-ALA-PDT group was given photosensitizer and light treatment at the same time. Flow cytometry was used to observe the apoptosis of HT-29 cells. Reverse transcription polymerase chain reaction (RT-PCR) was used to observe the expression of B-type lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax) in HT-29 cells. Ultraviolet spectrophotometry was used to detect the expression of Caspase-3. Results:The apoptotic rate of 5-ALA-PDT group was significantly higher than that of blank control group, 5-ALA group and PDT group ( P<0.05). Compared with the blank control group, 5-ALA-PDT group and PDT group, the expression of Bcl-2 in the 5-ALA-PDT group was statistically significant ( P<0.05), but there was no significant difference in Bax expression among the four groups ( P>0.05). The expression of Bax/Bcl-2 in 5-ALA-PDT group was significantly higher than that in blank control group, 5-ALA group and PDT group ( P<0.05). The expression of Caspase-3 in 5-ALA-PDT group was significantly higher than that in blank control group, 5-ALA group and PDT group ( P<0.05). Conclusions:5-ALA-PDT can induce apoptosis of HT-29 cells, and its mechanism may be related to the induction of apoptosis through Bax/Bcl-2 pathway.
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Objective:To investigate the changes of porphyrin metabolites in urine of patients with colorectal cancer before and after operation and their correlation with prognosis.Methods:One hundred patients with colorectal cancer were collected in First Affiliated Hospital of Hebei North University from June 2016 to December 2016, urine was collected before operation, 1 week after operation, 1 year after operation and before recurrence. The contents of urinary porphyrin metabolites of uroporphyrinogenI (UP Ⅰ) and coproporphyrinogen Ⅲ(CP Ⅲ) were detected by high performance liquid chromatography. Toanalyse the changes of UPⅠ and CPⅢ levels before and after operaction of colorectal cancer and their correlation with clinicopathologicalcharacteristics,and the recurrence and metastasis after operation.Results:The levels of UPⅠ and CPⅢ in urine of patients with colorectal cancer after operation were significantly lower than those before operation [(66.80 ± 17.62) μmol/g vs. (35.58 ± 9.32) μmol/g, (20.14 ± 3.14) μmol/g vs. (10.38 ± 0.85) μmol/g] ( P<0.05). The levels of UP Ⅰ and CP Ⅲ in urine of patients with Dukes C/D stage were significantly higher than those with Dukes A/B stage [(45.26 ± 5.26) μmol/g vs. (28.56 ± 3.45) μmol/g, (86.57 ± 6.58) μmol/g vs. (52.48 ± 3.36) μmol/g], the levels of UP Ⅰand CPⅢ in urine of patients with lymph node metastasis were significantly higher than those without lymph node metastasis [(45.44 ± 5.46) μmol/g vs. (30.27 ± 6.07) μmol/g, (86.67 ± 6.87) μmol/g vs. (56.10 ± 11.08) μmol/g], there were significant differences ( P<0.05). Urinary levels of UPⅠ and CPⅢ were independent risk factors for recurrence and metastasis of colorectal cancer after operation ( OR=1.149 and 1.065, P<0.05). Conclusions:Porphyrin metabolites (UPⅠ and CPⅢ) in urine may serve as a new marker for assessing colorectal cancer.
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Understanding the biomechanical properties of periodontal ligament is of great significance for orthodontic treatment. Due to the complexity of periodontal ligament structures, previous studies mainly used in vitro experiments, which had limitations. In order to obtain accurate and actual data, in vivo experiments on biomechanical properties of periodontal ligaments will become a trend of development in the future. In this article, the method, types, progress, advantages and disadvantages of in vivo experiments on biomechanical properties of periodontal ligaments were reviewed and prospected.
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Objective@#To study the application of urinary 5-aminolevulinic acid (5-ALA)detection in screening and identification of colorectal cancer and adenomatous polyps.@*Methods@#The clinical data of 500 high-risk patients(including 22 cases with colorectal cancer, 134 cases with adenomatous polyps, and 344 cases with other patients) at the First Affiliated Hospital of Hebei North University from January 2018 to October 2018 were collected. High performance liquid chromatography(HPLC) was used to detect urinary 5-ALA and fecal occult blood test was used to detect faeces. Sensitivity and specificity of two methods was compared. At the same time, urine samples of 431 cases(including 22 cases with colorectal cancer, 134 cases with adenomatous polyps and 275 cases with colorectal normal mucosa)were collected, and the difference of the content of urinary 5-ALA among three groups was compared.@*Results@#The sensitivity of urinary 5-ALA for the colorectal cancer screening was74.9%, and the specificity was 72.5%. The sensitivity of urinary 5-ALA for the adenomatous polyps screening was 70.1%, and the specificity was75.0%. The sensitivity of fecal occult blood test for the colorectal cancer screening was 63.6%, and the specificity was 62.1%. The sensitivity of fecal occult blood test for the adenomatous polyps screening was 42.3%, and the specificity was 62.5%. The content of urinary 5-ALA of the colorectal cancer group [(9.35 ± 0.46) μmol/g] was significantly higher than that of the adenomatous polyps group [(7.24 ± 0.64) μmol/g] (P < 0.05) and normal colorectal mucosa group [(3.12 ± 0.24) μmol/g] (P < 0.05), and the content of urinary 5-ALA of the adenomatous polyps group was significantly higher than that of colorectal normal mucosa group (P < 0.05).@*Conclusions@#For screening of colorectal cancer and adenomatous polyps, the content of urinary 5-ALA by HPLC is better than fecal occult blood test, and this approach can do great help to identify colorectal cancer, adenomatous polyps and normal colorectal mucosa.
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Objective To study the application of urinary 5-aminolevulinic acid (5-ALA) detection in screening and identification of colorectal cancer and adenomatous polyps. Methods The clinical data of 500 high-risk patients(including 22 cases with colorectal cancer, 134 cases with adenomatous polyps, and 344 cases with other patients) at the First Affiliated Hospital of Hebei North University from January 2018 to October 2018 were collected. High performance liquid chromatography (HPLC) was used to detect urinary 5-ALA and fecal occult blood test was used to detect faeces. Sensitivity and specificity of two methods was compared. At the same time, urine samples of 431 cases (including 22 cases with colorectal cancer, 134 cases with adenomatous polyps and 275 cases with colorectal normal mucosa)were collected, and the difference of the content of urinary 5-ALA among three groups was compared. Results The sensitivity of urinary 5-ALA for the colorectal cancer screening was 74.9% , and the specificity was 72.5% . The sensitivity of urinary 5-ALA for the adenomatous polyps screening was 70.1% , and the specificity was75.0% . The sensitivity of fecal occult blood test for the colorectal cancer screening was 63.6% , and the specificity was 62.1% . The sensitivity of fecal occult blood test for the adenomatous polyps screening was 42.3%, and the specificity was 62.5%. The content of urinary 5-ALA of the colorectal cancer group [(9.35 ± 0.46) μmol/g] was significantly higher than that of the adenomatous polyps group [(7.24 ± 0.64) μmol/g] (P<0.05) and normal colorectal mucosa group [(3.12 ± 0.24) μmol/g] (P<0.05), and the content of urinary 5-ALA of the adenomatous polyps group was significantly higher than that of colorectal normal mucosa group (P<0.05). Conclusions For screening of colorectal cancer and adenomatous polyps, the content of urinary 5-ALA by HPLC is better than fecal occult blood test, and this approach can do great help to identify colorectal cancer, adenomatous polyps and normal colorectal mucosa.
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Objective@#To explore the clinical features and prognostic factors of elderly MM patients.@*Methods@#A retrospectively analysis of clinical characteristics in 93 newly diagnosed MM patients with more than 70 years of old between August 2011 and August 2016. Based on age, basic activities of daily living scale, instrumental activities of daily living scale, Charlson comorbidity index at diagnosis, patients were divided into three groups: Fit (score=0, n=15) , Intermediate fitness (score=1, n=31) , Frail (score≥2, n=47) according to a geriatric assessment system proposed by Antonio Palumbo et al. The treatment response rate, progression free survival time (PFS) and overall survival (OS) of the three groups were analyzed.@*Results@#Complete remission was 60.0% in Fit, 22.6% in Intermediate fitness and 12.8% in Frail (Fisher χ2=12.398, P=0.002) . The median PFS for the three groups were 31 months, 24 months and 13 months (χ2=17.832, P<0.001) . The median OS was not reached for Fit, 58 months for Intermediate fitness and 25 months for Frail (χ2=40.678, P<0.001) . In 47 Frail cases, patients who received chemotherapy containing new drugs (proteasome inhibitor or immune-modulator) had a longer PFS (17 months vs 9 months, χ2=6.454, P=0.011) and patients who achieved CR had prolonged PFS and OS than non-CR (PFS: 24 months vs 12 months, χ2=4.117, P=0.042; OS: 37 months vs 25 months, χ2= 6.507, P=0.011) .@*Conclusion@#The health status of the elderly MM patients was associated with better response and longer PFS and OS. Given on those with poor health status, new drugs may have better PFS and prolonged OS.
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<p><b>OBJECTIVE</b>To observe treatment response, survival, safety and the improvement of ECOG in patients with refractory multiple myeloma (MM) with serious heart failure after the administration of continuous low-dose of cyclophosphamide combined with prednisone (CP).</p><p><b>METHODS</b>From January 2005 to September 2013, a total of 75 patients were treated by metronomic chemotherapy with continuous low-dose cyclophosphamide (50 mg/d) and prednisone (15 mg/d).</p><p><b>RESULTS</b>Among the 75 patients, 2 were lost for follow-up. In the 73 available patients, the overall response was 64.4%, including 2 patients (2.7%) with complete remission (CR), 4 cases (5.5%) very good partial remission (VGPR), and 24 patients (32.9%) partial remission (PR). The median survival was 12 months (1-70 months) with a median onset time of 90 days (16-120) and a median progressive freedom survival of 12 months (1-60). The level of B-type natriuretic peptide in responders declined significantly, as compared to no responders [(336.6 ± 30.3) ng/L vs (906.4 ± 104.8) ng/L, P<0.01]. Common adverse events were as follows: 32 (43.8%) cases of bone marrow suppression, 26 (35.6%) cases of infection, 8 cases of dizzy as well as sleepiness (11.0%), 7(9.6%) cases of Cushing syndrome, 4 (5.5%) cases of secondary diabetes mellitus, and 3 (4.1%) cases of edema respectively.</p><p><b>CONCLUSION</b>The metronomic chemotherapy of cyclophosphamide combined with prednisone had satisfactory impact on the treatment outcome, including the improvement of cardiac functions and physical capacities, better survival and safety in refractory MM with serious heart failure. It provides a novel regimen for such patients.</p>
Subject(s)
Humans , Antineoplastic Combined Chemotherapy Protocols , Clinical Protocols , Cyclophosphamide , Heart Failure , Multiple Myeloma , Prednisone , Remission Induction , Treatment OutcomeABSTRACT
Peripheral neuropathy (PN) is a major complication of multiple myeloma (MM),and is caused by MM itself and the drugs used to treat the disease.The complexity of PN differentials and subjective symptoms have made the diagnosis and treatment of PN difficult.
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Objective To evaluate the efficacy andtolerability of continuous low-dose cyclophosphamide and prednisone treatment of relapsed and refractory multiple myeloma. Methods84 relapsed and refractory multiple myeloma patients were enrolled, including 46 males and 38 females, the assess patients of 81 cases with average age of 69.7 (45-91)years. They were treated continuous with oral cyclophosphamide (50 mg/d) and prednisone (15 mg/d) and monthly follow-up.ResultsAverage follow-up time were 23.5(1-71)months.The assessed patients were 81 cases,with 52 cases (64.2 ％) responded.There were 2 cases(2.5 ％)CR,21 cases(25.9 ％) of PR,29 cases(35.8 ％)MR,19 cases(23.5 ％)NC and 10 cases (12.3 ％)PD.The median time to response was 2 months.In the patients who responded to the treatment,the median progression-free survival(PFS)and overall survival (OS) were 18(95 ％CI 12.8-23.2),29(95 ％CI 24.1-33.9)months.In the non-responding patients,the PFS and OS were 4(95 ％ CI 2.2-5.8) and 6(95 ％ CI 4.9-7.1)months.Two groups were statistically significant(P＜0.05).The most common toxicities included fatigue,nausea, neutropenia, hyperglycemia and lung infection. No patient withdrew from the study because of toxicity. Conclusions Continuous low-dose cyclophosphamide combined prednisone is a treatment options for relapsed and refractory MM patients.
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Objective To evaluate the efficacy and side effects of standard-dose of dexamethasone and low-dose dexamethasone combined with thalidomide in treatment of multiple myeloma. Methods Thirtynine patients with multiple myeloma were randomly divided into 2 groups, who were treated with chemotherapy of thalidomide (200 mg/d) plus dexamethasone (40 mg d1-46728 days in standard-dose group and 20 mg dl-4d/28 days in low-dose group), for a total of 4 courses. The efficacy, survival time and adverse events were compared between the two groups. Results Complete remission rate, partial remission rate and overall response rate of the standard-dose group were 26.3 %, 35 % and 75 %, respectively; and those of the low-dose group were 15.8% , 36.8 % and 68.4 %, respectively. No statistical difference between the two groups (P >0.05 ) was observed. Lung infections, blood pressure elevation, blood glucose elevation, shingles and other adverse reactions in the standard-dose group were statistically higher than those in the low-dose group (P <0.05). Conclusion Efficacy on multiple myeloma of standard-dose and low-dose dexamethasone are similar, but adverse reactions are significantly increased.
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Objective To assess the efficacy and tolerability of continuous low-dose cyclophosphamide and prednisone regimen(CP)as salvage therapy for multiple myeloma patients with severe complications.Methods The CP regimen consisted of oral cyclophosphamide at 50 mg and oral prednisone at 15 mg daily.The patients were withdrawn if the response was invalid or not improved after 6 months,and follow-up was carried on if CR maintained for 6 weeks.A total of 23 consecutive patients received the CP regimen,with 18 patients having severe complications,and 5 patients unwilling to accept conventional chemotherapy because of severe infection.All patients had received one to four regimens before.Results Among 23 patients with CP regimen,the overall response rate(CR+VGPR+PR)was 61%,with 1 CR,4 VGPR,9 PR,3 MR and 6 PD.The quality of life and physical conditions were improved significandy.Conclusion Our data showed that CP was an effective,well-tolerated,and convenient regimen as salvage therapy for MM with severe complications.