scholarly journals DICER1 mutation and pituitary prolactinoma

2018 ◽  
Vol 2018 ◽  
Author(s):  
Ellena Cotton ◽  
David Ray
Keyword(s):  
Case Reports ◽  
Early Death ◽  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
List Type ◽  
Non Coding Rna ◽  
Increased Risk ◽  
Non Coding Rnas ◽  
Learning Points

Summary A young woman carrying germline DICER1 mutation was discovered to have a pituitary microprolactinoma when she became amenorrhoic. The mutation was identified as a result of family screening following the early death of the patient’s daughter with ovarian cancer. The patient was in follow-up screening for thyroid disease, and investigations were initiated when she became amenorrhoic. MR scan revealed a 6 mm diameter pituitary microadenoma and raised prolactin. The prolactin was efficiently suppressed with low-dose cabergoline, and her menstrual cycles resumed. Dicer is an RNase enzyme, which is essential for processing small non-coding RNAs. These molecules play pleiotropic roles in regulating gene expression, by targeting mRNA sequences for degradation. DICER1 plays different roles depending on cell context, but is thought to be a functional tumour suppressor gene. Accordingly, germline mutation in one DICER1 allele is insufficient for oncogenesis, and a second hit on the other allele is required, as a result of postnatal somatic mutation. Loss of DICER1 is linked to multiple tumours, with prominent endocrine representation. Multinodular goitre is frequent, with increased risk of differentiated thyroid cancer. Rare, developmental pituitary tumours are reported, including pituitary blastoma, but not reports of functional pituitary adenomas. As DICER1 mutations are rare, case reports are the only means to identify new manifestations and to inform appropriate screening protocols. Learning points: DICER1 mutations lead to endocrine tumours. DICER1 is required for small non-coding RNA expression. DICER1 carriage and microprolactinoma are both rare, but here are reported in the same individual, suggesting association. Endocrine follow-up of patients carrying DICER1 mutations should consider pituitary disease.

scholarly journals Proteinuria in frasier syndrome

2013 ◽  
Vol 141 (9-10) ◽  
pp. 685-688
Author(s):  
Amira Peco-Antic ◽  
Fatih Ozaltin ◽  
Vojislav Parezanovic ◽  
Gordana Milosevski-Lomic ◽  
Verica Zdravkovic
Keyword(s):  
Renin Angiotensin System ◽  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
Frasier Syndrome ◽  
Angiotensin System ◽  
Increased Risk ◽  
Risk Of Malignancy ◽  
End Stage ◽  
Ras Inhibitors

Introduction. Frasier syndrome (FS) is a genetic form of glomerulopathy, which results from mutations in the Wilms? tumour suppressor gene (WT1). Proteinuria in FS has been traditionally considered unresponsive to any medication and FS inevitably progresses to end stage renal failure. Case Outline. We present a patient with FS who had atypical clinical manifestation and unusual beneficial antiproteinuric response to renin-angiotensin system (RAS) inhibitors given in combination with indomethacin. After 13 years of follow-up, the patient is now 17-year old with normal renal functions and no proteinuria. Conclusion. RAS inhibitors combined with indomethacin showed beneficial effect in our patient. Thus, this combination might be the initial treatment of patients with FS. If this treatment strategy was not satisfied for at least 3 months, then CsA would be considered to be administered taking account of the nephrotoxicity and the increased risk of malignancy. Further prospective study is required to clarify this issue.

scholarly journals Role of miR-193a in Cancer: Complexity and Factors Control the Pattern of its Expression

2018 ◽  
Vol 18 (7) ◽  
pp. 618-628 ◽  
Author(s):  
Afraa Mamoori ◽  
Vinod Gopalan ◽  
Alfred K-Y Lam
Keyword(s):  
Genetic Factors ◽  
Expression Patterns ◽  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
Epigenetic Factors ◽  
Biological Behaviour ◽  
Non Coding Rna ◽  
Different Types ◽  
Non Coding Rnas

Background: There is emerging data suggesting that the non-coding RNA (microRNA 193a or miR-193a) plays key roles in different types of cancers. Objective: This review aims to investigate the functional significance of miR-193a in different cancers according to the information of literature. Method: All the literature concerning miR-193a in cancer in PubMed are analysed. Results: Several studies proved the association of miR-193a expression patterns with cancer’s stages, grades, response to the chemotherapy and even patient survival. Also, miR-193a can be used to differentiate some types of cancer. In cancer, miR-193a can act as a tumour suppressor gene or as an oncogene. Till now, several genetic factors (MAX, RXR α, XB130, P63, P73, AEG-1, HIFs, EGFR, Drosha, DGCR8, Dicer) and epigenetic factors (DNA methylation and long non-coding RNAs) were predicted to control miR-193a expression. They have fundamental effects on its biological behaviour in different types of cancers. Conclusion: miR-193a has significant roles in cancer and can be targeted in the future for cancer therapy by better understanding of the factors that control its biological behaviour.

scholarly journals Orbital Leiomyosarcoma After Bilateral Retinoblastoma Treated With Chemotherapy And Radiotherapy

2020 ◽  
Vol 2 (3) ◽  
Author(s):  
Aoife Smyth ◽  
Elizabeth M. McElnea ◽  
Penelope McKelvie ◽  
Alan McNab
Keyword(s):  
Healthcare Professionals ◽  
Genetic Defect ◽  
Soft Tissue Sarcomas ◽  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
Secondary Malignancy ◽  
Bilateral Retinoblastoma ◽  
Increased Risk ◽  
One Year ◽  
Symptoms And Signs

A 23-year old man presented with a swelling medially in his left orbit. He had had bilateral retinoblastoma as an infant and was treated with bilateral enucleation, chemotherapy and radiotherapy. Histological examination confirmed the lesion to be leiomyosarcoma. A genetic defect in the RB1 tumour suppressor gene underlies the development of hereditary retinoblastoma and renders patients at substantially increased risk of developing subsequent non-ocular malignancies including soft tissue sarcomas. This risk is enhanced by radiotherapy particularly if administered before the age of one year. Awareness, by both patients and healthcare professionals, of this risk of secondary malignancy, is extremely important. Identification and aggressive investigation of new symptoms and signs may allow for the earlier detection of secondary malignancy which may, in turn, improve outcomes.

Is AraC Required In the Treatment of Standard Risk APL? Long Term Results of a Randomized Trial (APL 2000) From the French Belgian Swiss APL Group

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 13-13 ◽  
Author(s):  
Lionel Ades ◽  
Emmanuel Raffoux ◽  
Sylvie Chevret ◽  
Stephane de Botton ◽  
Agnes Guerci ◽  
...  
Keyword(s):  
Group Treatment ◽  
Early Death ◽  
Long Term Results ◽  
Newly Diagnosed ◽  
Treatment Regimens ◽  
Increased Risk ◽  
Wbc Count ◽  
Standard Risk

Abstract Abstract 13 Background: The combination of ATRA and anthracycline based chemotherapy (CT) is the reference induction and consolidation treatment of newly diagnosed APL. Whereas in high risk pts (ie with baseline WBC>10G/L), AraC is often considered useful in combination with an anthracycline to prevent relapse, CT with idarubicin alone appears sufficient to yield very low relapse rates in standard risk APL (with WBC< 10G/L) (Ades, Blood 2008, 111:1078-84). On the other hand our APL2000 trial, where standard risk pts were randomized between ATRA with DNR+AraC and ATRA with DNR without AraC, was prematurely terminated after the first interim analysis due to significantly more relapses and shorter survival in the arm without AraC (JCO 2006, 24:5703-10). We reevaluated those results, 6 years after the last patient inclusion. Methods In APL 2000 trial newly diagnosed APL patients < 60 years with WBC < 10G/L were randomized between the AraC+ group: induction with ATRA 45mg/m2/d until CR and DNR 60 mg/m2/d x3 + AraC 200mg/m2/d x7 started on day 3; first consolidation with the same CT course, second consolidation with DNR 45 mg/m2/d x3d and AraC 1g/m2/12h x4d; maintenance during two years with intermittent ATRA (15 d/ 3 months) and continuous 6 MP + MTX, and the AraC- group: same treatment, but without AraC. Pts < 60 years with WBC > 10 G/l (high WBC Group) were not randomized but received the AraC+ group treatment, but with higher AraC dose during the second consolidation (2 g/m2/12 hx 5 days). The current analysis was made at the reference date of 1 January 2010, 72 months after inclusion of the last pt. Results: Overall, 340 pts entered APL 2000 trial between July 2000 and Feb, 2004 (pts included in APL2000 trial after termination of inclusion in the AraC- group, until 2006 are not analyzed here). The AraC+ and AraC- groups (95 and 101 pts, resp) were well balanced for all pretreatment characteristics except WBC count that was higher in the AraC+ arm (mean 2.8 vs. 2.4 Giga/L). In the AraC+, group, 94 pts (99 %) achieved CR and one had early death (ED), as compared to 95 (94 %) CR in the AraC- group (p= 0.12), while there were 1 vs. 4 early deaths (ED), and 0 vs. 2 resistant leukemias in the two arms. The 5-year cumulative incidence of relapse, EFS and survival were 13.4 % vs. 29.0% (p = 0.013), 82.2% vs. 64.8% (p = 0.01), and 92.9% vs. 83.3% (p = 0.07) in the AraC + and AraC- group, respectively. Of the 23 relapses in the AraC- group, 20 were Hematological Relapses and 3 were Molecular Relapses, as compared to 10 and 2, respectively, for the 12 relapses in the AraC+ group. In the high WBC group (where there was no randomization and all pts received AraC), the CR rate, 5-year CIR, 5-year EFS and 5-year survival were 97%, 7.5%, 82.5%, and 89.8%, ie an outcome that appeared slightly superior to that of standard risk pts treated without AraC. Conclusion: With longer follow up, our findings suggest that, in standard risk APL(WBC < 10G/l), avoiding AraC for chemotherapy may lead to an increased risk of relapse when the anthracycline used is DNR. Our results caution against the use, in standard risk APL, of very effective treatment regimens without AraC like the PETHEMA 99 trial (Sanz, Blood 112:3130-34), but where idarubicin would be replaced by DNR. Disclosures: Fenaux: CELGENE, JANSSEN CILAG, AMGEN, ROCHE, GSK, NOVARTIS, MERCK, CEPHALON: Honoraria, Research Funding.

Outcome of congenital acute lymphoblastic leukemia treated on the Interfant-99 protocol

Blood ◽  
2009 ◽  
Vol 114 (18) ◽  
pp. 3764-3768 ◽  
Author(s):  
Marieke H. van der Linden ◽  
Maria Grazia Valsecchi ◽  
Paola De Lorenzo ◽  
Anja Möricke ◽  
Gritta Janka ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Case Reports ◽  
Lymphoblastic Leukemia ◽  
Early Death ◽  
Curative Intent ◽  
Treatment Delays ◽  
Strong Trend ◽  
B Lineage ◽  
Induction Failure

Abstract Acute lymphoblastic leukemia (ALL) diagnosed in the first month of life (congenital ALL) is very rare. Although congenital ALL is often assumed to be fatal, no studies have been published on outcome except for case reports. The present study reports the outcome of 30 patients with congenital ALL treated with the uniform Interfant-99 protocol, a hybrid regimen combining ALL treatment with elements designed for treatment of acute myeloid leukemia. Congenital ALL was characterized by a higher white blood cell count and a strong trend for higher incidence of MLL rearrangements and CD10-negative B-lineage ALL compared with older infants. Induction failure rate was 13% and not significantly different from that in older infants (7%, P = .14), but relapse rate was significantly higher in congenital ALL patients (2-year cumulative incidence [SE] was 60.0 [9.3] vs 34.2 [2.3], P < .001). Two-year event-free survival and survival of congenital ALL patients treated with this protocol was 20% (SE 9.1%). Early death in complete remission and treatment delays resulting from toxicity were not different. The survival of 17% after last follow-up, combined with a toxicity profile comparable with that in older infants, justifies treating congenital ALL with curative intent. This trial was registered at www.clinicaltrials.gov as no. NCT 00015873, and at www.controlled-trials.com as no. ISRCTN24251487.

scholarly journals Phaeochromocytoma presenting with polyuria: an uncommon presentation of a rare tumour

2014 ◽  
Vol 2014 ◽  
Author(s):  
N Atapattu ◽  
K A C P Imalke ◽  
M Madarasinghe ◽  
A Lamahewage ◽  
K S H de Silva
Keyword(s):  
Correct Diagnosis ◽  
List Type ◽  
Rare Tumour ◽  
Uncommon Presentation ◽  
The Family ◽  
History Of ◽  
Associated Conditions ◽  
Complete Physical Examination ◽  
Learning Points

Summary Children rarely present with phaeochromocytoma. Their presentation differs from that of adults. The classic triad of sweating, headache and palpitation may not always present in children with phaeochromocytoma. In this study, we present a 6-year-old girl who came to us with polyuria and polydipsia for evaluation of suspected diabetes insipidus. She gave a clear history of increased sweating in the recent past. On clinical examination, she was noted to have high blood pressure. Subsequent investigations revealed a phaeochromocytoma. Her polyuria and hypertension resolved immediately after the surgery. We did not have the facilities to arrange for genetic tests; however, the patient and the family members are under follow-up for other associated conditions. Learning points Polyuria and polydipsia are rare symptoms of phaeochromocytoma. Complete physical examination prevented unnecessary investigations for polyuria and led to a correct diagnosis. Classic features are not always necessary for diagnostic evaluation of rare diseases.

scholarly journals Genome-wide CNV study and functional evaluation identified CTDSPL as tumour suppressor gene for cervical cancer

2018 ◽  
Author(s):  
Dan Chen ◽  
Shuai Wang ◽  
Zhenli Li ◽  
Tao Cui ◽  
Yao Chen ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Hela Cells ◽  
Zinc Finger Protein ◽  
Tumour Volume ◽  
Suppressor Gene ◽  
Copy Number Variations ◽  
Tumour Suppressor Gene ◽  
Functional Evaluation ◽  
Nucleotide Polymorphisms ◽  
Increased Risk

AbstractWe have investigated copy number variations (CNVs) in relation to cervical cancer by analyzing 731,422 single-nucleotide polymorphisms (SNPs) in 1,034 cervical cancer cases and 3,948 controls, followed by replication in 1,396 cases and 1,057 controls. We found that a 6367bp deletion in intron 1 of the CTD small phosphatase like gene (CTDSPL) was associated with 2.54-fold increased risk of cervical cancer (odds ratio =2.54, 95% confidence interval =2.08-3.12, P=2.0×10−19). This CNV is one of the strongest genetic risk variants identified so far for cervical cancer. The deletion removes the binding sites of zinc finger protein 263, binding protein 2 and interferon regulatory factor 1, and hence downregulates the transcription of CTDSPL. HeLa cells expressing CTDSPL showed a significant decrease in colony-forming ability. Compared with control groups, mice injected with HeLa cells expressing CTDSPL exhibited a significant reduction in tumour volume. Furthermore, CTDSPL-depleted immortalized End1/E6E7 could form tumours in NOD-SCID mice.

scholarly journals Late presentation of acromegaly in medically controlled prolactinoma patients

2016 ◽  
Vol 2016 ◽  
Author(s):  
Ekaterina Manuylova ◽  
Laura M Calvi ◽  
Catherine Hastings ◽  
G Edward Vates ◽  
Mahlon D Johnson ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Dopamine Agonists ◽  
Late Presentation ◽  
List Type ◽  
Biochemical Control ◽  
Current Recommendation ◽  
Long Term Follow Up ◽  
Learning Points

Summary Co-secretion of growth hormone (GH) and prolactin (PRL) from a single pituitary adenoma is common. In fact, up to 25% of patients with acromegaly may have PRL co-secretion. The prevalence of acromegaly among patients with a newly diagnosed prolactinoma is unknown. Given the possibility of mixed GH and PRL co-secretion, the current recommendation is to obtain an insulin-like growth factor-1 (IGF-1) in patients with prolactinoma at the initial diagnosis. Long-term follow-up of IGF-1 is not routinely done. Here, we report two cases of well-controlled prolactinoma on dopamine agonists with the development of acromegaly 10–20 years after the initial diagnoses. In both patients, a mixed PRL/GH-cosecreting adenoma was confirmed on the pathology examination after transsphenoidal surgery (TSS). Therefore, periodic routine measurements of IGF-1 should be considered regardless of the duration and biochemical control of prolactinoma. Learning points: Acromegaly can develop in patients with well-controlled prolactinoma on dopamine agonists. The interval between prolactinoma and acromegaly diagnoses can be several decades. Periodic screening of patients with prolactinoma for growth hormone excess should be considered and can 
lead to an early diagnosis of acromegaly before the development of complications.

scholarly journals THE ALCOHOL CONSUMPTION IS AMENDED AFTER BARIATRIC SURGERY? AN INTEGRATIVE REVIEW

2016 ◽  
Vol 29 (suppl 1) ◽  
pp. 111-115 ◽  
Author(s):  
Valeria Duarte GREGORIO ◽  
Roselma LUCCHESE ◽  
Ivânia VERA ◽  
Graciele C. SILVA ◽  
Andrecia SILVA ◽  
...  
Keyword(s):  
Bariatric Surgery ◽  
Alcohol Consumption ◽  
Case Reports ◽  
Integrative Review ◽  
Alcohol Metabolism ◽  
Inclusion Criteria ◽  
Manual Search ◽  
Increased Risk ◽  
Postoperative Time

ABSTRACT Background Bariatric surgery has been an alternative when conservative methods of weight loss fail. Patients undergoing bariatric surgery have an increased risk of up to 6.5% of problems related to alcohol Objective: Integrative review out to analyze the change of alcohol consumption in this public Method: Database was accessed from June of 2015 to January of 2016 by searching "bariatric surgery" AND "alcoholism", and their Portuguese equivalents. ScienceDirect, PubMed, Lilacs and Medline, besides manual search, were searched. To be included, the paper should have been published between 2005-2016 and related to bariatric surgery and alcoholism. Theses, dissertations, unpublished papers, case reports and theoretical studies were excluded, and a database was subsequently composed Results: In 2005 there was only a review of change in alcohol metabolism in patients undergoing bariatric surgery. There were no publications in 2006. In 2007, only one study was published, and it did not meet the inclusion criteria. In 2010, there was an increase of 13% in publications and of 20% in 2012, reaching 40% in 2013 Conclusion: The prevalence and incidence of alcohol consumption in relation to the postoperative time was six months to three years with higher incidence for follow-up treatment by men. Roux-en-Y gastric bypass showed greater association with increased consumption of alcohol during the postoperative period. Alcohol consumption proved to be essential to be faced in bariatric surgery.

scholarly journals 035 Valproate-induced parkinsonism ‘an early warning’: case reports and review of literature

2019 ◽  
Vol 90 (e7) ◽  
pp. A12.2-A12
Author(s):  
Shoaib Dal ◽  
Scott Whyte
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Case Reports ◽  
The Elderly ◽  
Time Frame ◽  
List Type ◽  
Review Of The Literature ◽  
Hand Tremor ◽  
Wheel Rigidity

IntroductionWe describe two cases of valproate-induced parkinsonism, where the parkinsonian features develop after commencing valproate (VPA), in a time frame and manner well described by previous publications.1 In contrast to the published literature, that has short duration of follow-up, we have had a prolonged follow-up of these two cases, who initially improved on ceasing valproate, but then after a period progressed again, with the development of levodopa-responsive asymmetrical Parkinson’s disease.2Cases67 years old man, on VPA 500 mg twice a day for seizures since 2008, developed new rest, re-emergent left hand tremor and hypomimia in 2012. Within months, the parkinsonism progressed to decremental bradykinesia, cog-wheel rigidity and hypophonia. The symptoms initially improved with changing VPA to levetiracetam; however, the disease reappeared after 6 months and although levodopa-responsive, it has been progressive since then.88 years old man, on VPA 700 mg twice a day for seizures since 2010, developed upper limb decremental bradykinesia, cog-wheel rigidity, camptocormia and rest, re-emergent tremor in hands in 2011. The parkinsonism improved significantly with cessation of VPA; however, the disease re-emerged after 2 years and has been progressive since then.ConclusionVPA may be responsible for unmasking underlying subclinical parkinsonism and these patients represent an earlier onset of Parkinson’s disease related to VPA exposure, rather than a purely drug related parkinsonian dysfunction. These cases also highlight the importance of long-term follow up in VPA-induced parkinsonism. These observations are an important consideration for clinicians treating patients with parkinsonian features secondary to VPA exposure.ReferencesBrugger F, Bhatia KP, Besag FM. Valproate-associated parkinsonism: a critical review of the literature. CNS Drugs 2016;30(6):527–540.Mahmoud F, Tampi RR. Valproic acid-induced parkinsonism in the elderly: a comprehensive review of the literature. Am J Geriatr Pharmacother 2011;9(6):405–412.

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