Temozolomide, an alkylating agent, initially used in the treatment of gliomas was expanded to include pituitary tumors in 2006. After 12 years of use, temozolomide has shown a notable advancement in ...pituitary tumor treatment with a remarkable improvement rate in the 5-year overall survival and 5-year progression-free survival in both aggressive pituitary adenomas and pituitary carcinomas. In this paper, we review the mechanism of action of temozolomide as alkylating agent, its interaction with deoxyribonucleic acid repair systems, therapeutic effects in pituitary tumors, unresolved issues, and future directions relating to new possibilities of targeted therapy.
O 6 -Methylguanine-DNA-methyltransferase (MGMT) is a unique protein, which both repairs O 6 -alkylguanine lesions stoichiometrically without a multi-enzymatic pathway and self-inactivates. It has ...recently been linked
to the therapeutic success of alkylating agent chemotherapy, specifically temozolomide treatment. This drug affects the MGMT
pathway to induce cell death in tumor tissue. Low levels of functional MGMT have been correlated with success of treatment,
while high levels bring about failure of therapy. Expression of MGMT protein varies in normal and tumoral tissue. Furthermore,
its epigenetic silencing due to promoter methylation has been linked to its lack of expression in many types of tumor, including
gliomas. Great enthusiasm surrounds the utility of this protein in cancer treatment. Not only has there been success in manipulating
MGMT levels to enhance alkylating agent therapy, but studies also suggest a possible role of MGMT in protecting hematopoietic
cells from the myelosuppressive effects of high-dose chemotherapy. Innovative research into this protein will no doubt be
rewarding. This review presents a summary of what is known about this unique protein, including its structure, function in
its pathway, polymorphisms, expression in normal and tumoral tissue, relation to alkylating agent therapy, and possible future
applications.
Autophagy in the endocrine glands Weckman, Andrea; Di Ieva, Antonio; Rotondo, Fabio ...
Journal of molecular endocrinology,
04/2014, Volume:
52, Issue:
2
Journal Article
Peer reviewed
Open access
Autophagy is an important cellular process involving the degradation of intracellular components. Its regulation is complex and while there are many methods available, there is currently no single ...effective way of detecting and monitoring autophagy. It has several cellular functions that are conserved throughout the body, as well as a variety of different physiological roles depending on the context of its occurrence in the body. Autophagy is also involved in the pathology of a wide range of diseases. Within the endocrine system, autophagy has both its traditional conserved functions and specific functions. In the endocrine glands, autophagy plays a critical role in controlling intracellular hormone levels. In peptide-secreting cells of glands such as the pituitary gland, crinophagy, a specific form of autophagy, targets the secretory granules to control the levels of stored hormone. In steroid-secreting cells of glands such as the testes and adrenal gland, autophagy targets the steroid-producing organelles. The dysregulation of autophagy in the endocrine glands leads to several different endocrine diseases such as diabetes and infertility. This review aims to clarify the known roles of autophagy in the physiology of the endocrine system, as well as in various endocrine diseases.
DICER1 gene mutations in endocrine tumors Solarski, Michael; Rotondo, Fabio; Foulkes, William D ...
Endocrine-related cancer,
03/2018, Volume:
25, Issue:
3
Journal Article
Peer reviewed
Open access
In this review, the importance of the DICER1 gene in the function of endocrine cells is discussed. There is conclusive evidence that DICER1 mutations play a crucial role in the development, ...progression, cell proliferation, therapeutic responsiveness and behavior of several endocrine tumors. We review the literature of DICER1 gene mutations in thyroid, parathyroid, pituitary, pineal gland, endocrine pancreas, paragangliomas, medullary, adrenocortical, ovarian and testicular tumors. Although significant progress has been made during the last few years, much more work is needed to fully understand the significance of DICER1 mutations.
Aggressive pituitary adenomas have a high risk of recurrence, a lack of therapeutic response, and resistance to conventional treatment. So far, no satisfactory biomarkers are available for predicting ...their behavior. Some specific pituitary adenoma histotypes are more prone to follow an aggressive behavior. Pituitary carcinomas are rare and show cerebrospinal and/or systemic metastasis. They have worse prognosis than aggressive adenomas, and radiation is of limited use in their treatment.
Background
Electromyographic studies have shown that external anal sphincter activity is modified in response to distension in animals with spinal cord injury. Gonadotropin-releasing hormone and its ...agonist leuprolide acetate have neurotrophic properties in animals with spinal cord injury.
Aim
This study was to determine the effects of leuprolide acetate treatment on electromyographic activity of the external anal sphincter and anorectal manometry in ovariectomized rats with spinal cord injury.
Methods
Adult ovariectomized rats were divided in three groups: (a) sham of spinal cord injury, (b) spinal cord injury treated with saline solution, and (c) spinal cord injury treated with leuprolide acetate. The spinal cord injury was induced by clamping at level T9. Leuprolide acetate dosage of 10 μg/kg was proctored intramuscular for 5 weeks, commencing the day after the lesion. Electromyography of the external anal sphincter, anorectal manometry, and volume of the cecum were evaluated in all groups.
Results
The electromyographic study of the external anal sphincter activity showed a significant improvement in injured rats treated with leuprolide acetate. Manometric analysis and cecum volume data obtained in animals with leuprolide acetate were very similar to those found in the sham group.
Conclusions
These results demonstrate that leuprolide acetate treatment improves the neurogenic colon in ovariectomized rats with spinal cord injury.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Introduction
Histologic, immunohistochemical and electron microscopic studies have provided conclusive evidence that a marked diversity exists between tumors which secrete growth hormone (GH) in ...excess. GH cell hyperplasia can also be associated with acromegaly in patients with extrapituitary GH—releasing hormone secreting tumors or in familial pituitary tumor syndromes.
Materials and methods
A literature search was performed for information regarding pathology, GH-producing tumors and acromegaly.
Results
This review summarizes the current knowledge on the morphology of GH-producing and silent GH adenomas, as well as GH hyperplasia of the pituitary.
Conclusion
The importance of morphologic classification and identification of different subgroups of patients with GH-producing adenomas and their impact on clinical management is discussed.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Although the relationship between acromegaly and depression has been ascribed to the effects of chronic disease, the role of growth hormone (GH), and insulin like growth factor-1 (IGF-1) is not ...clear.
To determine whether related hormones levels in acromegalics are correlated with depressive symptoms and whether these symptoms are ameliorated following surgery.
A prospective cohort study was conducted on patients diagnosed with acromegaly (
= 15) or non-functioning pituitary adenomas (NFPA;
= 20, as controls) and undergoing first-time surgery, who completed the Center for Epidemiological Studies Depression (CES-D) questionnaire both pre-surgery and post-surgery. The primary outcome was the patient's severity of depression symptomatology using the CES-D score; GH, IGF-1 levels, and tumor characteristics were also measured.
Hormone levels (GH and IGF-1) and depression scores in acromegaly patients showed significant reductions following surgery (
< 0.05). The average change in CES-D score was 5.73 ± 2.58 (mean ± SE). A moderate correlation was found between GH levels and CES-D scores (
= 0.52,
< 0.01). The depressed affect subscale accounted for the most improvement in CES-D scores postoperatively and correlated most highly with GH levels. We did not find similar declines in the matched cohort of NFPA patients.
Surgical resection of the pituitary tumor in acromegaly patients leads to reduction in GH levels that is correlated with reduction in CES-D scores. The results suggest a role for GH in depression and provide a stronger foundation on which to build the hypothesis that GH impacts affect. The study also suggests that hormones should be factored into the matrix that entails the neuro-biological underpinnings of depressive disorders. Future work could explore the mechanisms involved, further brain and neuropeptide interactions, and, novel potential therapeutic targets in depressive and other mental health disorders.
Chronic subdural hematomas (CSDHs) are a common neurological condition, whose incidence is expected to increase with an aging population. Although surgical evacuation is the mainstay of treatment, it ...results in a recurrence requiring reoperation (RrR) in 3–30% of cases. Recurrence is thought to be driven by a combination of inflammatory and angiogenic processes occurring within the CSDH outer membrane. Pathological specimens of 72 primary CSDHs were examined for eosinophilic infiltrate. For each case, the pre-operative computed tomography (CT) scan was graded according to the Nakaguchi grading scheme as homogeneous, laminar, separated, or trabecular. Rate of RrR was compared based on eosinophilic infiltrate and CT grade. A dense eosinophilic infiltrate was observed in 22% of specimens. The rate of RrR among specimens with a dense eosinophilic infiltrate was 0%, whereas it was 14.3% among specimens without a dense eosinophilic infiltrate. Incidence among homogeneous, laminar, separated, and trabecular CT subtypes was 4%, 27%, 58%, and 24%, respectively. A dense eosinophilic infiltrate found within the outer membrane of a CSDH may be a marker of hematoma maturation, signaling a transition toward healing and fibrosis, and a lower risk of RrR.
Summary The behavior of clear cell renal cell carcinoma can be difficult to predict. Angiogenesis has proven to be a useful prognostic indicator in different malignancies. Endoglin (CD105) is a new ...marker of angiogenesis found to have prognostic utility in various tumors. Here, we provide the first automated digital assessment of intratumoral microvascular density in clear cell renal cell carcinoma using endoglin and CD31 and assess their utility as predictors of clinical outcome. Both endoglin and CD31 expression showed association with advanced tumor stage ( P = .025 and P = .011, respectively). There was a significant correlation between CD31 and tumor grade ( P = .034). Kaplan-Meier survival curves showed that patients with higher endoglin expression had significantly shorter progression-free survival ( P = .010). Patients with higher CD31 expression tended to have a worse prognosis, although this was not statistically significant ( P = .082). In univariate analysis using endoglin as a continuous variable, increased endoglin was strongly associated with reduced survival (hazard ratio, 1.74; 95% CI, 1.39-2.18; P = <.001). CD31 also correlated with poor outcomes (hazard ratio, 1.52; 95% CI, 1.24-1.86; P = .001). There was no correlation between CD31 and endoglin expression ( r = −0.090, P = .541). Receiver operating characteristic analysis showed the area under the curve to be 0.749 for endoglin and 0.550 for CD31. In conclusion, increased endoglin and CD31 expression are associated with a higher tumor stage and decreased progression-free survival. Our automated approach overcomes many limitations of manual quantification. Advances in digital assessment of immunohistochemical markers can be helpful in standardizing the evaluation of tumor biomarkers.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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