scholarly journals Characterization of a base-resolution common deletion region within CDKN2A gene in cancers and its biological and clinical significances

Author(s):  
Juanli Qiao ◽  
Rui Xing ◽  
Zhiyuan Fan ◽  
Jing Zhou ◽  
Yuan Tian ◽  
...  

Background: Frequency of somatic copy number deletion of CDKN2A gene is upto 60% in human esophageal squamous cell cancer. However, it is unknown whether CDKN2A deletion could be a biomarker for esophageal squamous cell dysplasia (ESCdys) due to absence of a feasible detection method. Methods: Information on base-resolution common deletion region (CDR) for CDKN2A were extracted from published articles and confirmed with whole genome sequencing (WGS). A quantitative PCR targeted to the CDR (P16-Light) was established and used to detect CDKN2A copy number in ESCdys biopsies from patients (n=205) enrolled in a multicentre follow-up study. Results: A 5.1-kb CDR from the CDKN2A/P16INK4A promoter to intron-2 was firstly characterized in 90% (83/92) of cancer cell lines and confirmed with WGS. The CDR covers CDKN2A exon-2 which is the essential coding exon for both P16INK4a and P14ARF. And CDKN2A exon-2 deletion markedly promoted the proliferation and invasion and inhibited the apoptosis of HEK293T cells. In the follow-up study, both somatic CDKN2A deletion and amplification are prevalent in mild/moderate (m/M) ESCdys. CDKN2A deletion was less common among 70 patients whose ESCdys regressed than among 135 patients whose ESCdys progressed or remained stable, and CDKN2A amplification was more common in the patients who regressed than in the patients whose m/M ESCdys persisted or progressed over a median of 37 months of follow-up (p<0.0001). Conclusion: There is A 5.1-kb CDR within CDKN2A gene in many cancers. CDR deletion could inactivate both P16INK4a and P14ARF and associate with prognosis of ESCdys.

2021 ◽  
Vol 8 (25) ◽  
pp. 2149-2154
Author(s):  
Alok Ranjan ◽  
Nisha Khanna ◽  
Vivek Ranjan ◽  
Ashwin Kumar

BACKGROUND Rasburicase (recombinant urate oxidase) has been proven to be an effective therapy for prevention of tumour lysis syndrome (TLS). The recommended daily dosing regimen of rasburicase is 0.2 mg/kg/day for 5 days which is expensive and unaffordable to many patients in the developing countries. The purpose of the present study was to evaluate the effect of single 1.5 mg dose rasburicase in the management of tumour lysis syndrome. METHODS This is a follow-up study done at our institute. Fifty (50) patients with tumour lysis syndrome who received rasburicase from August 2015 to January 2020 were enrolled in this study RESULTS Single dose of rasburicase is effective in decreasing serum uric acid level in significant number (N = 41) of patients. Percentage of patients having uric acid less than 7 mg after single dose of rasburicase in 48 hours - 82.9 % (N = 34) while 17 % (N = 7) were found to have uric acid levels of more than 7 mg/dl. The percentage of patients with uric acid levels more than 7 mg/dl reduced from 36.5 % after 24 hours to 17 % after 48 hours. This indicates that the uric acid levels show a declining trend even after 24 hours without giving an additional dose of rasburicase. There was no relationship between uric acid levels at 24 hours and percentage change in creatinine level from baseline to 24 hours (correlation coefficient (r) = -0.047, P = 0.770. Patients who required additional dose (N = 9) had high base line value of uric acid and their high value was maintained over the follow up period of three days. Patients with pre exiting kidney disease and high level of baseline uric acid also needed dialysis (N = 3). CONCLUSIONS In majority of patients, a single 1.5 mg dose of rasburicase is an effective way to reduce raised uric acid in appropriate circumstances. KEYWORDS Single Dose, Recombinant Urate Oxidase, Uric Acid, Leukemia, Tumour Lysis Syndrome, Rasburicase


Author(s):  
Etsuo Murata ◽  
Kazutaka Tokita ◽  
Shigeyuki Tsurusaki ◽  
Hidetaka Murata

We have developed ethanol therapy for infectious atheroma based on the experience of two cases in which ethanol was injected into the liver cyst and the cyst shrank. For 64 infectious atheromas, atheroma contents were excreted and the cyst wall was contacted with 76% ethanol gauze for 5 minutes. Postoperatively, the cyst was washed daily as an open drainage. All cases were cured 10 days postoperatively, and no side effects. Postoperative follow up study results in 36 cases showed no recurrence in an average of 5 years. Pathological examination revealed koilocytosis in 14 of 25 cases (56%), which is considered to be an in direct finding of viral infection. The changes in human papillomavirus (HPV 16) before and after ethanol therapy in 25 cases using the Bi Digital O Ring Test (BDORT) decreased significantly from 10 26 ng (BDORT units) preoperatively to 1.6 ng (BDORT units) postoperatively. In also 12 cases follow up study without microscopy HPV 16 same decreased from 1064ng to 1.2 ng (BDORT unit) using BDORT with atheroma photographs. In total, HPV 16 could be demonstrated in 37 of 64 cases (57.8%) using BDOR T. Temporal changes of HPV 16 used for BDORT in 7 cases after contact with ethanol were inactivated after 3 minutes 30 seconds. The involvement of HPV 16 is suggested as the cause of atheroma. It is speculated that ethanol inactivated HPV 16 of atheroma, which stopped the turnover of the squamous epithelium and prevented recurrence. Ethanol therapy for infectious atheroma is useful as an original new one stage surgery because it is a simple procedure and has no side effects or recurrence.


Diabetes Care ◽  
1992 ◽  
Vol 15 (4) ◽  
pp. 525-527 ◽  
Author(s):  
R. E. Maser ◽  
D. J. Becker ◽  
A. L. Drash ◽  
D. Ellis ◽  
L. H. Kuller ◽  
...  

2017 ◽  
Vol 89 (10) ◽  
pp. 17-21 ◽  
Author(s):  
L L Bolotskaya ◽  
E G Bessmertnaya ◽  
M V Shestakova ◽  
M Sh Shamkhalova ◽  
L V Nikankina ◽  
...  

Aim. To assess the time course of changes in the level of glycated hemoglobin (HbA1c) for 20 years after the onset of type 1 diabetes mellitus (T1DM) and to compare its correlation with the development of microvascular complications, such as diabetic retinopathy (DR) and diabetic nephropathy (DN). Subjects and methods. A total of 187 children with new-onset T1DM were registered in Moscow in 1994. During the 20-year follow-up study, these patients underwent regular check-ups at the Endocrinology Research Center, Ministry of Health of the Russian Federation, which included assessment of physical data, HbA1c 2-4 times a year, biochemical blood and albuminuria tests (once per year), and ophthalmologic examination (twice a year). A total of 155 people fully completed the 20-years follow-up study. Results. During the 20-year follow-up period after the onset of T1DM, 86 of the 155 patients developed microvascular complications: DR and DN in 86 (55.5%) and 24 (15.5%) cases, respectively; while DR concurrent with DN were noted in 20 patients. By the time of their last visit, 69 (44.5%) patients had no evidence suggesting the presence of microvascular complications. The level of HbA1c at the onset of the disease in patients who later developed the complications was higher than in those without complications (10.2±0.6 and 8.5±0.2%, respectively (p = 0.003). The statistically significant differences in HbA1c levels between the groups persisted during subsequent 15 years of follow-up, averaging 9.2±1.5, 9.7±0.9, and 8.1±0.7% after 5, 10, and 15 years, respectively, in the complication group and 7.1±0.3, 8.1±0.4, and 7.2±0.2% in the non-complication group (p < 0.01). Over the last 5 years of the follow-up, the mean HbA1c level between the groups was not significantly different, which at the end of the 20-year follow-up period was 7.8±0.3 and 7.4±0.6%, respectively (p > 0.05). The mean duration of T1DM, in which DR developed, was 9.6±6.2, 11.0±2.0, and 13.6±4.6 years for the non-proliferative, pre-proliferative, and proliferative stages, respectively. That of T1DM, in which DN developed, was 11.8±0.6 years for microalbuminuria and 16.1±1.3 years for macroalbuminuria. Conclusion. The 20-year clinical follow-up of patients who had fallen ill with T1DM in childhood showed that diabetic microangiopathies developed with the long-term preservation of poor blood glucose control (BGC) starting at the onset of the disease. At the same time, the complications progressed to more severe stages, despite a clear trend toward better BGC. This may be suggestive of the negative metabolic memory phenomenon, which necessitates stable BGC, starting at the onset of the disease, for the prevention of microvascular complications.


Ophthalmology ◽  
2020 ◽  
Author(s):  
Oren Tomkins-Netzer ◽  
Susan L. Lightman ◽  
Alyce E. Burke ◽  
Elizabeth A. Sugar ◽  
Lyndell L. Lim ◽  
...  

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