Similar response to therapy of pituitary adenomas with and without SOX2-expressing cells

2013 ◽  
Author(s):  
Mihail Coculescu ◽  
Anca Campean ◽  
Cristina Stancu ◽  
Cristina Capatina ◽  
Gheorghiu Monica Livia ◽  
...  
Keyword(s):  
Pituitary Adenomas ◽  
Response To Therapy ◽  
Similar Response

scholarly journals Adoptive therapy with CMV-specific cytotoxic T lymphocytes depends on baseline CD4+ immunity to mediate durable responses

2021 ◽  
Vol 5 (2) ◽  
pp. 496-503
Author(s):  
Vanessa A. Fabrizio ◽  
M. Irene Rodriguez-Sanchez ◽  
Audrey Mauguen ◽  
Parastoo B. Dahi ◽  
Ekaterina Doubrovina ◽  
...  
Keyword(s):  
Overall Survival ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Hematopoietic Cell Transplantation ◽  
Adoptive Cell Therapy ◽  
Response To Therapy ◽  
Third Party ◽  
Similar Response ◽  
Adoptive Therapy ◽  
Initiation Of Therapy

Abstract Adoptive cell therapy using cytomegalovirus (CMV)-specific cytotoxic T lymphocytes (CMV-CTLs) has demonstrated efficacy posttransplant. Despite the predicted limited engraftment of CMV-CTLs derived from third-party donors, partially matched third-party donor–derived CMV-CTLs have demonstrated similar response rates to those derived from primary hematopoietic cell transplantation donors. Little is known about the mechanisms through which adoptive cellular therapies mediate durable responses. We performed a retrospective analysis of patients receiving CMV-CTLs for treatment of CMV viremia and/or disease after allogeneic transplant between September of 2009 and January of 2018. We evaluated whether response to adoptively transferred CMV-CTLs correlated with immune reconstitution (IR), using validated CD4+ IR milestones of 50 × 106/L and 200 × 106/L. In this analysis, a cohort of 104 patients received CMV-CTLs derived from a primary transplant donor (n = 25), a third-party donor (n = 76), or both (n = 3). Response to therapy did not increase the likelihood of achieving CD4+ IR milestones at 1 (P = .53 and P > .99) or 2 months (P = .12 and P = .33). The origin of CMV-CTLs did not impact subsequent CD4+ IR. CMV-CTLs appeared to interact with host immunity in mediating responses. Recipients with a baseline CD4 >50 × 106/L had higher response to therapy (P = .02), improved overall survival (P < .001), and protection from CMV-related death (P = .002). Baseline endogenous immunity appears to improve CMV-related and overall survival in this cohort and can be an important marker at the initiation of therapy.

scholarly journals REVA: a rank-based multi-dimensional measure of correlation

2018 ◽  
Author(s):  
Bahman Afsari ◽  
Alexander Favorov ◽  
Elana J. Fertig ◽  
Leslie Cope
Keyword(s):  
Cancer Cells ◽  
Correlation Coefficient ◽  
Cancer Biology ◽  
Expression Profiles ◽  
Correlation Coefficients ◽  
Response To Therapy ◽  
Similar Response ◽  
Finite Sample ◽  
Distance Correlation ◽  
Two Samples

AbstractThe neighbors principle implicit in any machine learning algorithm says that samples with similar labels should be close to one another in feature space as well. For example, while tumors are heterogeneous, tumors that have similar genomics profiles can also be expected to have similar responses to a specific therapy. Simple correlation coefficients provide an effective way to determine whether this principle holds when features and labels are both scalar, but not when either is multivariate. A new class of generalized correlation coefficients based on inter-point distances addresses this need and is called “distance correlation”. There is only one rank-based distance correlation test available to date, and it is asymmetric in the samples, requiring that one sample be distinguished as a fixed point of reference. Therefore, we introduce a novel, nonparametric statistic, REVA, inspired by the Kendall rank correlation coefficient. We use U-statistic theory to derive the asymptotic distribution of the new correlation coefficient, developing additional large and finite sample properties along the way. To establish the admissibility of the REVA statistic, and explore the utility and limitations of our model, we compared it to the most widely used distance based correlation coefficient in a range of simulated conditions, demonstrating that REVA does not depend on an assumption of linearity, and is robust to high levels of noise, high dimensions, and the presence of outliers. We also present an application to real data, applying REVA to determine whether cancer cells with similar genetic profiles also respond similarly to a targeted therapeutic.Author summarySometimes a simple question arises: how does the distance between two samples in multivariate space compare to another scalar value associated with each sample. Here, we propose theory for a nonparametric test to statistically test this association. This test is independent of the scale of the scalar data, and thus generalizable to any comparison of samples with both high-dimensional data and a scalar. We apply the resulting statistic, REVA, to problems in cancer biology motivated by the model that cancer cells with more similar gene expression profiles to one another can be expected to have a more similar response to therapy.

scholarly journals Temozolomide therapy for aggressive functioning pituitary adenomas refractory to surgery and radiation: a case series

2017 ◽  
Vol 5 (1) ◽  
pp. 64-68 ◽  
Author(s):  
Justin T Jordan ◽  
Julie J Miller ◽  
Tucker Cushing ◽  
Marlon Seijo ◽  
Tracy T Batchelor ◽  
...  
Keyword(s):  
Pituitary Adenomas ◽  
Case Series ◽  
Pituitary Tumors ◽  
Retrospective Chart Review ◽  
Progression Free Survival ◽  
Response To Therapy ◽  
Chemotherapeutic Regimen ◽  
Free Survival ◽  
Tumor Pathology ◽  
Multimodality Approach

Abstract Background Treatment of aggressive pituitary adenomas typically involves a multimodality approach based on histopathological features and may include pharmacotherapy, surgery, and occasionally radiation therapy. In cases of treatment-refractory tumor progression, chemotherapy may be considered; however, no standard chemotherapeutic regimen has been established. Literature review suggests that temozolomide may have a beneficial role in a subset of cases. To understand the efficacy of temozolomide in progressive pituitary tumors, we reviewed the outcomes of cases at our center. Methods We performed a retrospective chart review to report the outcome and unique features of 7 patients with aggressive functioning pituitary adenomas or carcinomas treated with temozolomide. Tumor pathology included somatotroph (n = 1), corticotroph (n = 3), and lactotroph (n = 3) tumors. Results Four of the 7 patients had at least 2 prior resections, and all had prior radiation and surgery before treatment with temozolomide. Notably, all patients showed response to therapy, defined as either stable disease (43%) or partial response (57%). Median progression-free survival was 1.66 years, and median overall survival was 4 years. Conclusion Our data suggest that temozolomide has an important role in the management of aggressive functioning pituitary tumors that are resistant to standard therapies, and that optimization of therapy with temozolomide may involve individualized regimens. Future prospective clinical trials should be considered.

Good usage of epoetin alpha biosimilar: A subanalysis of the orheo study.

2014 ◽  
Vol 32 (31_suppl) ◽  
pp. 217-217 ◽  
Author(s):  
Mauricette Michallet ◽  
Pierre Soubeyran ◽  
Elisabeth Luporsi ◽  
Jean-Emmanuel Kurtz ◽  
Helene Albrand
Keyword(s):  
Response To Therapy ◽  
Solid Tumours ◽  
Recommended Dose ◽  
Similar Proportion ◽  
Similar Response ◽  
Patients With Cancer ◽  
Epoetin Alpha ◽  
Post Marketing ◽  
Colorectal Lymphoma ◽  
Clinical Trial Information

217 Background: Chemotherapy-induced anaemia (CIA) is a frequent complication of patients with cancer. The ORHEO (place of biOsimilaRs in the therapeutic management of anaemia secondary to chemotherapy in HaEmatology and Oncology) study was a post-marketing, observational, multicentre study conducted in France that evaluated the changes in haemoglobin (Hb) level in patients with solid tumours, lymphoma or myeloma, treated with an epoetin alfa biosimilar (EAB) (Retacrit, Hospira Inc.). In this subanalysis of the ORHEO study, we compare the usage of EAB in relation to the dosage recommendations of the European Organisation for Research and Treatment of Cancer (EORTC) guidelines, regarding two criteria: efficacy and safety profile. Methods: Patients with CIA receiving chemotherapy for solid tumours (breast, lung, colorectal), lymphoma or myeloma, and prescribed EAB were monitored at the start of the EAB therapy (D0), at 3 months (M3) and 6 months (M6). Hb response was defined as achievement of target Hb without blood transfusions in the preceding 3 weeks and during treatment or Hb ≥10 g/dL orHb increase ≥1 g/dL since inclusion. The prescribed dosage of EAB according to body weight and the tolerability of EAB at that recommended dosage were analysed at each time point. Results: Data from 2310 patients were analysed. Throughout the study 43.8% of patients received the recommended dose of EAB as determined by their weight. Overall, the percentage of responders was 81.6% at M3 and 86.5% at M6. Responses to treatment (meeting predefined Hb target levels) at M6 were similar whether or not EAB was prescribed at the recommended dose throughout the study. A similar proportion of patients receiving the recommended dose of EAB reported adverse events (AEs) at M6 compared with patients who did not receive the recommended dose (9.9% vs 9.0%). Overall, the incidence of thromboembolic events was 3.5% over the duration of the study (M3 2.4%; M6 1.5%). Conclusions: Of the 2310 patients with CIA included in this analysis, less than half (43.8%) received the recommended dose of EAB over the six-month course of the study. The majority of patients had a similar response to therapy regardless of dose. The frequency of overall AEs at M6 did not vary depending on dose. Clinical trial information: NCT02140736.

scholarly journals Quantitative analysis of somatostatin receptor subtype (SSTR1–5) gene expression levels in somatotropinomas and non-functioning pituitary adenomas

2007 ◽  
Vol 156 (1) ◽  
pp. 65-74 ◽  
Author(s):  
Giselle F Taboada ◽  
Raul M Luque ◽  
Wildebranham Bastos ◽  
Renata F C Guimarães ◽  
Jorge B Marcondes ◽  
...  
Keyword(s):  
Pituitary Adenomas ◽  
Somatostatin Receptor ◽  
Response To Therapy ◽  
Receptor Subtype ◽  
Mrna Levels ◽  
Octreotide Lar ◽  
Variable Expression ◽  
Igf I ◽  
Percent Decrease ◽  
Non Functioning Pituitary Adenomas

Objective: It is believed that the variable effectiveness of somatostatin analogs in post-surgical management of somatotropinomas and non-functioning pituitary adenomas (NFPA) may be due in part to variable expression of somatostatin receptor isoforms (SSTR1–5), within and between pituitary tumor types. Design and methods: Quantitative real-time RT-PCR was used to compare absolute mRNA copy numbers for all five SSTR isoforms in 23 somatotropinomas and 19 NFPA. Results: Somatostatin receptor subtype 5 mRNA was present at the highest level in somatotropinomas, followed by SSTR2>SSTR3≫SSTR1⋙SSTR4. In contrast, SSTR3 mRNA was present at the highest level in NFPA, followed by SSTR2, while SSTR1, SSTR4, and SSTR5 transcripts were only detectable in select tumors. Among somatotropinomas, a positive correlation was found between SSTR2 mRNA levels and the percent decrease of GH (%GH) after 3 and 6 months of therapy with octreotide long acting repeatable (LAR) (r=0.51 and r=0.66; P=0.05 and P=0.008). Also the percent decrease of IGF-I (%IGF-I) after 3 months of octreotide LAR was negatively correlated with SSTR5 and %IGF-I after 6 months of octreotide LAR was positively correlated with SSTR2. Conclusions: The present report is a large series examining SSTR mRNA levels in somatotropinomas and NFPA. These initial findings suggest that detailed knowledge of the SSTR mRNA expression profile in somatotropinomas can help to predict the hormonal response to therapy with LAR. Also, it appears that SSTR3 in NFPA may be a potential target for SSTR3 preferential or universal ligands such as pasireotide.

scholarly journals Low- Versus High-Dose Radiotherapy for Graves’ Ophthalmopathy: A Randomized, Single Blind Trial

2000 ◽  
Vol 85 (1) ◽  
pp. 102-108 ◽  
Author(s):  
George J. Kahaly ◽  
Hans-Peter Rösler ◽  
Susanne Pitz ◽  
Gerhard Hommel
Keyword(s):  
Rectus Muscle ◽  
Response To Therapy ◽  
High Dose ◽  
Similar Response ◽  
Eye Muscle ◽  
Orbital Radiotherapy ◽  
Graves Ophthalmopathy ◽  
Significant Amelioration ◽  
Group A ◽  
Satisfaction Rates

Orbital radiotherapy (Rx) is a commonly used treatment for Graves’ ophthalmopathy (GO), but controlled clinical trials evaluating different Rx doses and application forms have not been performed. In euthyroid patients with moderately severe GO, we randomly compared the efficacy and tolerability of three Rx protocols. Orbital Rx (telecobalt) was administered either in 20 divided fractions of 1 Gray (Gy) weekly over 20 weeks (group A) or in 10 fractions of 1 Gy (B) and 2 Gy (C) daily over 2 weeks. Before and 24 weeks after starting Rx, ophthalmic investigation and magnetic resonance imaging were performed. Response to therapy, defined as a significant amelioration of three objective parameters, was noted in 12 A (67%), 13 B (59%), and 12 C (55%) subjects (C vs. A, P = 0.007). Ophthalmic symptoms and signs regressed most in group A; changes in lid fissure width were −1.5, −0.5, and 0 mm in the A, B, and C groups, respectively (A vs. C, P = 0.005), whereas changes in intraocular pressure (upgaze) were −3, +1, and −1.5 mm Hg, respectively (A vs. B, P = 0.002). The median decreases in proptosis were −2 mm (A, P = 0.0001),− 1.5 mm (B, P = 0.02), and −1 mm (C, P = 0.007; A vs. C, P = 0.0380. Visual acuity (+0.15; P = 0.02) and eye muscle motility (bulbar elevation, 30° vs. 37°, P = 0.03, A vs. C, P = 0.0020; abduction, 45 vs. 49°, P = 0.02; A vs. C, P = 0.017) improved in group A only. A significant change in all rectus muscle areas was noted in 14 A (78%), 12 B (55%), and 9 C (41%) subjects (C vs. A, P = 0.002). A decrease in the NOSPECS classes was observed in 12 A (67%), 13 B (59%), and 13 C (59%) patients (A vs. B/C, P = 0.01). Rx-induced conjunctivitis was not observed in group A, but was seen in 4 B (18%) and 8 C (36%) subjects (C vs. A, P= 0.003). At 24 weeks, satisfaction rates were 67%, 59%, and 55% in the A, B, and C groups, respectively (C vs. A, P = 0.008). Thus, in patients with moderately severe GO, similar response rates were observed for low and high Rx doses, but the 1 Gy/week protocol was more effective and better tolerated than the short arm regimens.

Ultrastructural Investigation of Spontaneous Pituitary Adenomas in Aging Sprague-Dawley Rats

1982 ◽  
Vol 40 ◽  
pp. 216-217
Author(s):  
D. J. McComb ◽  
J. Beri ◽  
F. Zak ◽  
K. Kovacs
Keyword(s):  
Microscopic Study ◽  
Pituitary Adenomas ◽  
Wistar Rats ◽  
Microscopic Level ◽  
Sprague Dawley ◽  
Prolactin Cells ◽  
Light Microscopic Level ◽  
Ultrastructural Investigation ◽  
Sprague Dawley Rats ◽  
Long Evans

Investigation of the spontaneous pituitary adenomas in rat have been limited mainly to light microscopic study. Furth et al. (1973) described them as chromophobic, secreting prolactin. Kovacs et al. (1977) in an ul trastructural investigation of adenomas of old female Long-Evans rats, found that they were composed of prolactin cells. Berkvens et al. (1980) using immunocytochemistry at the light microscopic level, demonstrated that some spontaneous tumors of old Wistar rats could contain GH, TSH or ACTH as well as PRL.

Ultrastructural comparison of prolactin adenomas of pituitary in men and women

1988 ◽  
Vol 46 ◽  
pp. 346-347
Author(s):  
R.C. Caughey ◽  
U.P. Kalyan-Raman
Keyword(s):  
Endoplasmic Reticulum ◽  
Electron Microscope ◽  
Phosphate Buffer ◽  
Pituitary Adenomas ◽  
Osmium Tetroxide ◽  
Secretory Granules ◽  
Uranyl Acetate ◽  
En Bloc ◽  
Men And Women ◽  
Transmission Electron

Prolactin producing pituitary adenomas are ultrastructurally characterized by secretory granules varying in size (150-300nm), abundance of endoplasmic reticulum, and misplaced exocytosis. They are also subclassified as sparsely or densely granulated according to the amount of granules present. The hormone levels in men and women vary, being higher in men; so also the symptoms vary between both sexes. In order to understand this variation, we studied 21 prolactin producing pituitary adenomas by transmission electron microscope. This was out of a total of 80 pituitary adenomas. There were 6 men and 15 women in this group of 21 prolactinomas.All of the pituitary adenomas were fixed in 2.5% glutaraldehyde, rinsed in Millonig's phosphate buffer, and post fixed with 1% osmium tetroxide. They were then en bloc stained with 0.5% uranyl acetate, rinsed with Walpole's non-phosphate buffer, dehydrated with graded series of ethanols and embedded with Epon 812 epoxy resin.

Fine Structural Classification of Chromophobe Adenomas of the Human Pituitary Gland

1975 ◽  
Vol 33 ◽  
pp. 378-379
Author(s):  
K. Kovacs ◽  
E. Horvath
Keyword(s):  
Pituitary Adenomas ◽  
Secretory Activity ◽  
Microscopic Investigation ◽  
Uranyl Acetate ◽  
Electron Microscopic Investigation ◽  
Electron Microscopic ◽  
Human Pituitary ◽  
Cytoplasmic Staining ◽  
Human Pituitary Gland ◽  
Microscopic Features

Chromophobe pituitary adenomas arise from adenohypophysial cells and fail to exhibit cytoplasmic staining with conventional acid or basic dyes by light microscopy. The aim of the present work was to study the electron microscopic features of these tumors, to separate them into distinct entities and to correlate their fine structural appearances with secretory activity.Among 48 surgically removed various pituitary adenomas 30 tumors were found which, based on the tinctorial characteristics of the cytoplasm, corresponded to chromophobe adenomas. For electron microscopic investigation pieces of these tumors were fixed in 2.5 per cent glutaraldehyde in Sorensen's buffer, post fixed in 1 per cent osmium tetroxide in Millonig's buffer, dehydrated in graded ethanol and embedded in Epon 812. Ultrathin sections were stained with uranyl acetate and lead citrate.By electron microscopy it was possible to separate chromophobe adenomas into 3 distinct entities: 1) adenomas consisting of sparsely granulated growth hormone cells (7 cases).

Ultrastructural Immunocytochemistry of Five Rat Pituitary Adenomas

1980 ◽  
Vol 38 ◽  
pp. 724-725
Author(s):  
D. J. McComb ◽  
N. Ryan ◽  
E. Horvath ◽  
K. Kovacs ◽  
E. Nagy ◽  
...  
Keyword(s):  
Pituitary Adenomas ◽  
Pituitary Tumors ◽  
Electron Microscopic ◽  
Electron Microscopic Immunocytochemistry ◽  
Transmission Electron ◽  
Rat Pituitary ◽  
Radiation Induced ◽  
Group 5 ◽  
Group 2 ◽  
Microscopic Techniques

Conventional light and electron microscopic techniques failed to clarify the cellular composition and derivation of spontaneous and induced, intrasellar and transplanted pituitary adenomas in rats (1). In the present work, electron microscopic immunocytochemistry was applied to evaluate five adenohypo-physial tumors using a technique described by Moriarty and Garner (2). Spontaneously occurring pituitary adenomas (group 1) were harvested from aging female Long-Evans rats. R-Amsterdam rats were treated with 2 x 1.0 mg estrone acetate (HogivaI) s.c. weekly for 6 months. Pituitary adenomas in excess of 30 mg were removed from these animals to make up the tumors of group 2. Groups 3 and 4 consisted of estrogen-induced autonomous transplan¬ted pituitary tumors MtT.WlO and MtT.F4. Group 5 was a radiation-induced transplanted autonomous pituitary tumor MtT.W5. The tumors of groups 3,4 and 5 were allowed to proliferate in host rats 6-8 weeks prior to removal for processing. Tissue was processed for transmission electron microscopy (glutaraldehyde fixation, OsO4 postfixation and epoxy resin embedding), and electron microscopic immunocytochemistry (3% paraformaldehyde fixation and Araldite embedding).

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