Pineal Tumors and Associated Lesions: The Effect of Ethnicity on Tumor Type and Treatment

2003 ◽  
Vol 38 (6) ◽  
pp. 307-323 ◽  
Author(s):  
David S. Knierim ◽  
Shokei Yamada
Keyword(s):  
Tumor Type ◽  
Pineal Tumors ◽  
Associated Lesions

Ultrastructural investigation of spontaneous pituitary gonadotroph cell adenomas in aging Sprague-Dawley rats

1983 ◽  
Vol 41 ◽  
pp. 702-703
Author(s):  
D. J. McComb ◽  
J. Beri ◽  
F. Zak ◽  
K. Kovacs
Keyword(s):  
Electron Microscopy ◽  
Animal Model ◽  
Epoxy Resin ◽  
Immunoelectron Microscopy ◽  
Tumor Type ◽  
Gonadal Function ◽  
Sprague Dawley ◽  
Male And Female ◽  
Reticulin Fibers ◽  
Sprague Dawley Rats

Gonadotroph cell adenomas of the pituitary are infrequent in human patients and are not invariably associated with altered gonadal function. To date, no animal model of this tumor type exists. Herein, we describe spontaneous gonadotroph cell adenomas in old male and female Sprague-Dawley rats by histology, immunocytology and electron microscopy.The material consisted of the pituitaries of 27 male and 38 female Sprague Dawley rats, all 26 months of age or older, removed at routine autopsy. Sections of formal in-fixed, paraffin-embedded tissue were stained with hematoxylin-phloxine-saffron (HPS), the PAS method and the Gordon-Sweet technique for the demonstration of reticulin fibers. For immunostaining, sections were exposed to anti-rat β-LH, anti-ratβ-TSH, anti-rat PRL, anti-rat GH and anti-rat ACTH 1-39. For electron microscopy, tissue was fixed in 2.5% glutaraldehyde, postfixed in 1% OsO4 and embedded in epoxy-resin. Tissue fixed in 10% formalin, embedded in epoxy resin without osmification, was used for immunoelectron microscopy.

The Role of Arthroscopy in the Treatment of Gouty Arthritis of the Knee Case presentation

2018 ◽  
Vol 69 (8) ◽  
pp. 2236-2239
Author(s):  
Marius Moga ◽  
Mark Edward Pogarasteanu ◽  
Dumitru Ferechide ◽  
Antoine Edu ◽  
Chen Feng Ifrim
Keyword(s):  
Gouty Arthritis ◽  
Surgical Techniques ◽  
Term Treatment ◽  
Clinical Aspects ◽  
Associated Lesions ◽  
Number Of Patients ◽  
Long Term Treatment ◽  
Functional Scores ◽  
Urate Crystals

Gout is a metabolic disease involving the impregnation of joints and other tissues with urate crystals. The onset is often brutal, and it manifests itself with pain and inflammation in the affected joint. The treatment usually involves rest, ice, NSAIDs and anti-gout medication. The long-term treatment involves medication and dietary changes. In the joint, urate crystals are deposited in the synovial, in the cartilage and in the menisci. In the arthroscopic practice, the gouty knee is a rare occurrence. We present a relevant case, that of a 57 years old patient without a prior gout diagnosis where we found urate crystal deposits covering the synovium, cartilage and meniscus, and we discuss the current and recent year Pub Med indexed literature in order to evaluate the possibilities for arthroscopic treatment of this pathology. We looked at the number of patients involved, their characteristics, and the surgical techniques used. We also looked at the temporal relation of the arthroscopic intervention to the recent gout attacks, and at the described lesions that were found. Also, we evaluated the papers for joint liquid analysis, gout drug treatment, and description of clinical aspects involved and associated lesions. Finally, we looked at the follow-up, at the functional scores used to monitor the patient�s evolution, at the associated medication and at the long-term outcomes, if described. We have found opinions to vary. In the end, we draw conclusions pertaining to the practical short-term and long-term use of knee arthroscopy in the treatment of gout.

The Tumor Suppressor Role of the Ras Association Domain Family 10

2020 ◽  
Vol 20 (18) ◽  
pp. 2207-2215
Author(s):  
Yulong Hou ◽  
Shuofeng Li ◽  
Wei Du ◽  
Hailong Li ◽  
Rumin Wen
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Gene Promoter ◽  
Disease Free Survival ◽  
Suppressor Gene ◽  
Detection Methods ◽  
Tumor Type ◽  
Domain Family ◽  
Invasion And Migration ◽  
Cancer Breast

The Ras association domain family 10(RASSF10), a tumor suppressor gene, is located on human chromosome 11p15.2, which is one of the members homologous to other N-terminal RASSF families obtained through structural prediction. RASSF10 plays an important role in inhibiting proliferation, invasion, and migration, inducing apoptosis, making cancer cells sensitive to docetaxel, and capturing G2/M phase. Some studies have found that RASSF10 may inhibit the occurrence and development of tumors by regulating Wnt/β-catenin, P53, and MMP2. Methylation of tumor suppressor gene promoter is a key factor in the development and progression of many tumors. Various methylation detection methods confirmed that the methylation and downregulation of RASSF10 often occur in various tumors, such as gastric cancer, lung cancer, colon cancer, breast cancer, and leukemia. The status of RASSF10 methylation is positively correlated with tumor size, tumor type, and TNM stage. RASSF10 methylation can be used as a prognostic factor for overall survival and disease-free survival, and is also a sign of tumor diagnosis and sensitivity to docetaxel chemotherapy. In this review, we mainly elucidate the acknowledged structure and progress in the verified functions of RASSF10 and the probably relevant signaling pathways.

scholarly journals QOL-36. USE OF CANNABINOIDS IN THE PEDIATRIC CENTRAL NERVOUS SYSTEM TUMOR POPULATION

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii438-iii438
Author(s):  
Kathleen Dorris ◽  
Jessica Channell ◽  
Ashley Mettetal ◽  
Molly Hemenway ◽  
Natalie Briones ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Central Nervous System ◽  
Nervous System ◽  
Cell Activity ◽  
Cns Tumors ◽  
Low Grade ◽  
Tumor Type ◽  
Central Nervous System Tumor ◽  
The Impact

Abstract BACKGROUND Cannabinoids, including cannabidiol (CBD) and tetrahydrocannabinol (THC), are a class of compounds found in marijuana. Numerous studies in adults have examined cannabinoid use in management of cancer-related symptoms such as nausea, anorexia, and pain. Less is known about the use in the pediatric oncology population. METHODS A prospective observational study has been ongoing since 2016 at Children’s Hospital Colorado to evaluate cannabinoids’ impact using PedsQL™ modules on quality of life of pediatric patients with central nervous system (CNS) tumors who are 2–18 years old. Laboratory assessments of T-cell activity and pharmacokinetics of CBD, THC and associated metabolites are in process. Diaries with exploratory information on cannabinoid use patterns are being collected. RESULTS Thirty-three patients (14:19; male:female) have been enrolled with a median age of 6.4 years (range, 2.9–17.7 years). The most common tumor type in enrolled patients is embryonal tumors (13/33; 39%). Nine (27%) patients have low-grade glial/glioneuronal tumors, and eight (24%) had high-grade/diffuse midline gliomas. The remaining patients had ependymoma or craniopharyngioma. The median time on cannabinoids is 9 months. Most (n=20) patients have used oral products with CBD and THC. One patient continues on cannabinoid therapy in follow up. Preliminary immune function analyses identified impaired neutrophil superoxide anion production and chemotaxis in patients taking cannabinoids at early time points on therapy. CONCLUSIONS Families of children with various CNS tumors are pursuing cannabinoid therapy for both antitumor and supportive care purposes. Analysis of the impact of cannabinoids on patients’ quality of life is ongoing.

scholarly journals Intrabodies targeting human papillomavirus 16 E6 and E7 oncoproteins for therapy of established HPV-associated tumors

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Francesca Paolini ◽  
Carla Amici ◽  
Mariantonia Carosi ◽  
Claudia Bonomo ◽  
Paola Di Bonito ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Antitumor Activity ◽  
Tumor Growth ◽  
Tumor Progression ◽  
Cellular Transformation ◽  
Neoplastic Progression ◽  
Single Chain ◽  
Hpv16 E6 ◽  
Associated Lesions ◽  
E6 And E7

Abstract Background The oncogenic activity of the high risk human papillomavirus type 16 (HPV16) is fully dependent on the E6 and E7 viral oncoproteins produced during viral infection. The oncoproteins interfere with cellular homeostasis by promoting proliferation, inhibiting apoptosis and blocking epithelial differentiation, driving the infected cells towards neoplastic progression. The causal relationship between expression of E6/E7 and cellular transformation allows inhibiting the oncogenic process by hindering the activity of the two oncoproteins. We previously developed and characterized some antibodies in single-chain format (scFvs) against the HPV16 E6 and E7 proteins, and demonstrated both in vitro and in vivo their antitumor activity consisting of protective efficacy against tumor progression of HPV16-positive cells. Methods Envisioning clinical application of the best characterized anti-HPV16 E6 and –HPV16 E7 scFvs, we verified their activity in the therapeutic setting, on already implanted tumors. Recombinant plasmids expressing the anti-HPV16 E6 scFvI7 with nuclear targeting sequence, or the anti-HPV16 E7 scFv43M2 with endoplasmic reticulum targeting sequence were delivered by injection followed by electroporation to three different preclinical models using C57/BL6 mice, and their effect on tumor growth was investigated. In the first model, the HPV16+ TC-1 Luc cells were used to implant tumors in mice, and tumor growth was measured by luciferase activity; in the second model, a fourfold number of TC-1 cells was used to obtain more aggressively growing tumors; in the third model, the HPV16+ C3 cells where used to rise tumors in mice. To highlight the scFv possible mechanism of action, H&E and caspase-3 staining of tumor section were performed. Results We showed that both the anti-HPV16 E6 and HPV16 E7 scFvs tested were efficacious in delaying tumor progression in the three experimental models and that their antitumor activity seems to rely on driving tumor cells towards the apoptotic pathway. Conclusion Based on our study, two scFvs have been identified that could represent a safe and effective treatment for the therapy of HPV16-associated lesions. The mechanism underlying the scFv effectiveness appears to be leading cells towards death by apoptosis. Furthermore, the validity of electroporation, a methodology allowed for human treatment, to deliver scFvs to tumors was confirmed.

scholarly journals Machine learning analysis using 77,044 genomic and transcriptomic profiles to accurately predict tumor type

2021 ◽  
Vol 14 (3) ◽  
pp. 101016 ◽  
Author(s):  
Jim Abraham ◽  
Amy B. Heimberger ◽  
John Marshall ◽  
Elisabeth Heath ◽  
Joseph Drabick ◽  
...  
Keyword(s):  
Machine Learning ◽  
Tumor Type ◽  
Learning Analysis

scholarly journals Pan-cancer analysis of CD274 (PD-L1) mutations in 314,631 patient samples and subset correlation with PD-L1 protein expression

2021 ◽  
Vol 9 (6) ◽  
pp. e002558
Author(s):  
Richard S.P. Huang ◽  
Brennan Decker ◽  
Karthikeyan Murugesan ◽  
Matthew Hiemenz ◽  
Douglas A. Mata ◽  
...  
Keyword(s):  
Protein Expression ◽  
Checkpoint Inhibitors ◽  
Endometrial Adenocarcinoma ◽  
Primary Melanoma ◽  
B Cell Lymphoma ◽  
Unknown Primary ◽  
Future Research ◽  
Tumor Type ◽  
Missense Mutations ◽  
L1 Protein

BackgroundThe effects of non-amplification short variant (SV) mutations in CD274 (programmed death-ligand 1 (PD-L1)) on PD-L1 protein expression and immune checkpoint inhibitors (ICPIs) therapy are unknown. Here, we present a retrospective analysis of CD274 mutations detected by comprehensive genomic profiling (CGP) and correlate these results with tumor-cell PD-L1 immunohistochemistry (IHC)-based expression assessment to better understand the relationship between mutations and protein expression of PD-L1.MethodsCGP was performed on hybridization-captured, adaptor ligation-based libraries using DNA and/or RNA extracted from 314,631 tumor samples that were sequenced for up to 406 cancer-related genes and select gene rearrangements. PD-L1 IHC was performed on a subset of cases (n=58,341) using the DAKO 22C3 PD-L1 IHC assay and scored with the tumor proportion score (TPS).ResultsOverall, the prevalence of CD274 SV mutations was low (0.3%, 1081/314,631) with 577 unique variants. The most common CD274 SV mutations were R260H (n=51), R260C (n=18), R125Q (n=12), C272fs*13 (n=11), R86W (n=10), and R113H (n=10). The prevalence of CD274 mutations varied depending on tumor type with diffuse large B-cell lymphoma (1.9%, 19/997), cutaneous squamous cell carcinoma (1.6%, 14/868), endometrial adenocarcinoma (1.0%, 36/3740), unknown primary melanoma (0.9%, 33/3679), and cutaneous melanoma (0.8%, 32/3874) having the highest frequency of mutations. Of the R260H cases concurrently tested with PD-L1 IHC, most (81.8%, 9/11) had no PD-L1 expression, which contrasts to the five E237K cases where most (80%, 4/5) had PD-L1 expression. In addition, we saw a significantly lower level of PD-L1 expression in samples with a clonal truncating variant (nonsense or frameshift indel) when compared with samples with a subclonal truncating variants (mean: TPS=1 vs TPS=38; p<0.001), and also in clonal versus subclonal missense mutations (mean: TPS=11 vs TPS=22, respectively; p=0.049)ConclusionsWe defined the landscape of CD274 mutations in a large cohort of tumor types that can be used as a reference for examining CD274 mutations as potential resistance biomarkers for ICPI. Furthermore, we presented novel data on the correlation of CD274 mutations and PD-L1 protein expression, providing important new information on the potential functionality of these mutations and can serve as a basis for future research.

scholarly journals Extrapolation of pharmacokinetics and pharmacodynamics of sunitinib in children with gastrointestinal stromal tumors

2021 ◽  
Author(s):  
Reza Khosravan ◽  
Steven G. DuBois ◽  
Katherine Janeway ◽  
Erjian Wang
Keyword(s):  
Body Size ◽  
Solid Tumors ◽  
Gastrointestinal Stromal Tumors ◽  
Drug Exposure ◽  
Tumor Type ◽  
Plasma Drug ◽  
Safety And Efficacy ◽  
Stromal Tumors ◽  
Mixed Effects Modeling ◽  
Starting Dose

Abstract Purpose The starting dose of sunitinib in children with gastrointestinal stromal tumors (GIST) was extrapolated based on data in adults with GIST or solid tumors and children with solid tumors. Methods Integrated population pharmacokinetics (PK), PK/pharmacodynamics (PD), and exposure–response analyses using nonlinear mixed-effects modeling approaches were performed to extrapolate PK and PD of sunitinib in children with GIST at projected dose(s) with plasma drug exposures comparable to 50-mg/day in adults with GIST. The analysis datasets included PK/PD data in adults with GIST and adults and children with solid tumors. The effect of covariates on PK and safety/efficacy endpoints were explored. Results Two-compartment models with lag time were successfully used to describe the PK of sunitinib and its active metabolite SU012662. PK/PD models were successfully built to describe key continuous safety and efficacy endpoints. The effect of age on sunitinib apparent clearance (CL/F) and body surface area on SU012662 CL/F was statistically significant (P ≤ 0.001): children who were younger or of smaller body size had lower CL/F; however, age and body size did not appear to negatively affect safety or efficacy response to plasma drug exposure. Conclusion Based on PK, safety, and efficacy trial simulations, a sunitinib starting dose of ~ 25 mg/m2/day was predicted to provide comparable plasma drug exposures in children with GIST as in adults with GIST treated with 50 mg/day. However, in the absence of a tumor type effect of sunitinib on CL/F in children, the projected equivalent dose for this population would be ~ 20 mg/m2/day.

scholarly journals Risk Factors for NON-HPV16/18 Cervical Infections and Associated Lesions Among HPV-DNA-Negative Women Vaccinated Against HPV16/18 in the Costa Rica Vaccine Trial (CVT)

2020 ◽  
Author(s):  
Mónica S Sierra ◽  
Sabrina H Tsang ◽  
Shangying Hu ◽  
Carolina Porras ◽  
Rolando Herrero ◽  
...  
Keyword(s):  
Sexual Behavior ◽  
Vaccine Trial ◽  
Smoking Behavior ◽  
Related Factors ◽  
Hpv Dna ◽  
Associated Lesions ◽  
Risk Of Progression ◽  
Specific Incident ◽  
Injectable Contraceptives ◽  
Baseline Bmi

Abstract Background Factors that lead human papillomavirus (HPV) infections to persist and progress to cancer are not fully understood, especially among vaccinated women. We evaluated co-factors for acquisition, persistence and progression of non-HPV16/18 infections in a cohort of HPV-vaccinated women. Methods We analyzed 2,153 18-25-year-old women randomized to the HPV-vaccine arm of CVT. Women were HPV-DNA-negative for all types at baseline and followed for ~11 years. Acquisition was a type-specific cervical infection not present/detected at the previously scheduled visit. Persistence was a type-specific incident infection that persisted for ≥1-year with no intervening negatives. Progression of persistent incident infections to CIN2+ was based on histological findings by expert pathologists. GEE methods were used to account for correlated observations. Time-dependent factors evaluated were age, sexual behavior, marital status, hormonal-related factors, number of full-term pregnancies (FTP), smoking behavior, and baseline-BMI. Results 1,777 incident oncogenic non-HPV16/18 infections were detected in 12,292 visits (average 0.14 infections per visit). Age and sexual behavior-related variables were associated with oncogenic non-HPV16/18 acquisition. 26% of incident infections persisted for ≥1-year. None of the factors evaluated were statistically associated with persistence of oncogenic non-HPV16/18 infections. Risk of progression to CIN2+ increased with increasing age (p-trend=0.001), injectable contraceptives use [relative risk 2.61 (95%CI 1.19–5.73) ever vs. never] and increasing FTP (p-trend=0.034). Conclusion In a cohort of HPV16/18-vaccinated women, age and sexual behavior variables are associated with acquisition of oncogenic non-HPV16/18 infections, no notable factors are associated with persistence of acquired oncogenic non-HPV16/18 infections, and age, parity and hormonally-related exposures are associated with progression to CIN2+.

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