-
International Journal of Molecular... Feb 2021The altered cell cycle is associated with aberrant growth factor signaling in somatotroph adenoma, which is the primary cause of acromegaly. The aim of the present study...
The altered cell cycle is associated with aberrant growth factor signaling in somatotroph adenoma, which is the primary cause of acromegaly. The aim of the present study was to investigate the pathological role of the INK4 family and evaluate the effectiveness of CDK4 inhibitor, palbociclib, in somatotroph adenoma. RNA‑Seq, RT‑PCR, and immunohistochemistry were applied to measure the levels and correlations of the INK4 family with angiogenesis, CDKs, EMT, and therapeutic targets. MTS, flow cytometry, and ELISA were used to investigate the bio‑activity in GH3 and GT1‑1 cell lines after palbociclib treatment. Compared with lactotroph adenoma, gonadotroph adenoma, and corticotroph adenoma, somatotroph samples demonstrated higher expression of CDKN2A and SSTR2 but a lower expression of EGFR, CDK4, and CDH2 (P<0.05). CDKN2A positively correlates with SSTR2, and negatively with CDK4, EGFR, and CDH2. Patients with lower CDKN2A had larger tumor size (P=0.016) and more invasive potential (P=0.023). Palbociclib inhibited cell proliferation, induced G1 phase arrest, reduced GH/IGF‑1 secretion of GH3 and GT1‑1 cell lines (P<0.05), and had a more prominent role in GH3 cells (P<0.05). CDKN2A inhibited the bio‑activity by modulating CDK4, and high CDKN2A predicted the insensitivity to CDK4 inhibitor, palbociclib, in somatotroph adenoma patients. In summary, the present study shows CDKN2A inhibited the bio‑activity by modulating CDK4, and high CDKN2A predicts the insensitivity to CDK4 inhibitor, Palbociclib, in somatotroph adenoma patients.
Topics: Adenoma; Adult; Antineoplastic Agents; Cell Line, Tumor; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase Inhibitor p16; Female; G1 Phase Cell Cycle Checkpoints; Growth Hormone-Secreting Pituitary Adenoma; Humans; Male; Middle Aged; Piperazines; Pyridines
PubMed: 33416096
DOI: 10.3892/ijmm.2020.4807 -
Pituitary Feb 2021Pathogenic variants in the aryl hydrocarbon receptor-interacting protein (AIP) gene are increasingly recognised as a cause of familial isolated pituitary adenoma....
Pathogenic variants in the aryl hydrocarbon receptor-interacting protein (AIP) gene are increasingly recognised as a cause of familial isolated pituitary adenoma. AIP-associated tumours are most commonly growth hormone (GH) producing. In our cohort of 175 AIP mutation positive patients representing 93 kindreds, 139 (79%) have GH excess, 19 have prolactinoma (17 familial and 2 sporadic cases) and out of the 17 clinically non-functioning tumours 4 were subsequently operated and found to be GH or GH & prolactin immunopositive adenoma. Here we report a family with an AIP variant, in which multiple family members are affected by prolactinoma, but none with GH excess. To our knowledge this is the first reported family with an AIP pathogenic variant to be affected solely by prolactinoma. These data suggest that prolactinoma families represent a small subset of AIP mutation positive kindreds, and similar to young-onset sporadic prolactinomas, AIP screening would be indicated.
Topics: Adenoma; Adult; Female; Genetic Testing; Growth Hormone-Secreting Pituitary Adenoma; Humans; Male; Middle Aged; Mutation; Pedigree; Pituitary Neoplasms; Prolactinoma
PubMed: 33010004
DOI: 10.1007/s11102-020-01085-5 -
Reviews in Endocrine & Metabolic... Jun 2020Pituitary tumors are not rare if prevalence rates from autopsy or radiological series are considered; approximately 0.5% of all pituitary adenomas will come to medical... (Review)
Review
Pituitary tumors are not rare if prevalence rates from autopsy or radiological series are considered; approximately 0.5% of all pituitary adenomas will come to medical attention. Less than 0.1% of these pituitary adenomas will become malignant, and probably around 0.5% of all detected adenomas will display an aggressive course. However, the exact incidence of both aggressive pituitary adenomas and pituitary carcinomas is unknown, as most data come from series with selected patients, such as surgically treated patients, which is likely not a reflection of all patients with a pituitary adenoma. An aggressive pituitary adenoma is not well-defined; even though an overarching definition, capturing both immunohistochemical and clinical characteristics is probably not waterproof, adoption of a widely accepted definition will be very helpful to harmonize research and establish more reliable epidemiological data.
Topics: Adenoma; Humans; Neoplasm Invasiveness; Pituitary Neoplasms
PubMed: 32361816
DOI: 10.1007/s11154-020-09556-7 -
Computational Intelligence and... 2022The first-line treatment for patients with any type of pituitary adenoma is trans-sphenoidal surgery. Considering the prevalence of the condition globally, the treatment... (Meta-Analysis)
Meta-Analysis Review
Recurrence Rate and Exploration of Clinical Factors after Pituitary Adenoma Surgery: A Systematic Review and Meta-Analysis based on Computer Artificial Intelligence System.
BACKGROUND
The first-line treatment for patients with any type of pituitary adenoma is trans-sphenoidal surgery. Considering the prevalence of the condition globally, the treatment is quite common. The recurrence of pituitary adenoma is a recognized occurrence in the medical field; however, there is limited comprehensive research and analysis of the predictive factors of recurrence rates and the clinical factors impacting relapse rates. Identifying the recurrence rates of pituitary adenomas and the clinical factors associated with them could help increase the remission rate by increasing focus on the specific aspects for early diagnosis and improved treatment.
OBJECTIVE
The objective of the current systematic review and meta-analysis is to assess the recurrent rates based on previous studies and to explore the clinical factors after pituitary surgery.
METHODS
A search was performed on PubMed, APA PsycINFO, Scopus, CENTRAL, and Google Scholar databases for English articles published from 1 January 2010 to 1 August 2022. Systematic reviews, meta-analysis, evidence syntheses, editorials, commentaries, preclinical studies, abstracts, theses, and preprints were excluded. Meta XL statistical software was used to conduct a prevalence meta-analysis.
RESULTS
PubMed, PsycINFO, and Medline databases were searched. All of the articles were written between 2012 and 2022. In the beginning, 612 items were recognized. After removing duplicates and analyzing the remaining articles in terms of inclusion and exclusion criteria, 31 articles remained.
CONCLUSION
There is a relationship between recurrence rates and the follow-up period. There were conflicting results about the clinical factors after pituitary adenoma surgery, specifically age and tumor size. Some included studies that there was an association between macroadenomas and high recurrence rates. No study reported that gender was a clinical factor affecting pituitary adenoma surgery outcomes or the recurrence rate. Studies also reported that there was a correlation between the remnant tumor factor and the recurrence rates; adenoma remnants after surgery increased the risk of recurrence rates for patients.
Topics: Humans; Pituitary Neoplasms; Artificial Intelligence; Adenoma; Computers
PubMed: 36275975
DOI: 10.1155/2022/6002672 -
BMC Cancer Oct 2023Accumulating studies have suggested metabolic syndrome (MetS) contributed to colorectal cancer (CRC) development. However, advanced CRC might decrease the detection...
BACKGROUND
Accumulating studies have suggested metabolic syndrome (MetS) contributed to colorectal cancer (CRC) development. However, advanced CRC might decrease the detection proportion of MetS due to chronic malnutrition, we included patients with early-stage CRC to examine the associations among MetS, onset age, and different tumorigenesis pathways of CRC.
METHODS
We conducted a retrospective study that included 638 patients with early-stage CRC from January 2014 to December 2018. Patient information was collected from the medical record system and further refined during the follow-up. Stratified analyses of the associations between MetS and different stratification factors were determined by the Cochran‒Mantel‒Haenszel test.
RESULTS
There were 16 (13.3%) and 111 (21.4%) cases suffering from MetS in the early-onset and late-onset CRC groups, respectively. MetS coexisted in early-stage CRC patients ≥ 50 years of age more frequently than patients < 50 years of age (OR 1.77; 95% CI 1.01 to 3.12), but not for women patients (OR 0.84; 95% CI 0.79 to 0.90). MetS patients were associated with a higher risk of advanced serrated lesions than that of conventional adenomas (OR 1.585; 95% CI 1.02 to 2.45), especially in patients ≥ 50 years (OR 1.78; 95% CI 1.11 to 2.85).
CONCLUSIONS
Metabolic dysregulation might partly contribute to the incidence of colorectal serrated lesions. Prevention of MetS should be highly appreciated in the early diagnosis and early treatment of the colorectal cancer system, especially in patients ≥ 50 years.
Topics: Humans; Female; Middle Aged; Metabolic Syndrome; Retrospective Studies; Adenoma; Colorectal Neoplasms; Incidence; Risk Factors; Colonoscopy
PubMed: 37872512
DOI: 10.1186/s12885-023-11537-3 -
Gut Microbes 2021Colorectal cancer (CRC) is a heterogeneous disease with different gene expression patterns. There are two major colorectal carcinogenesis pathways: conventional... (Review)
Review
Colorectal cancer (CRC) is a heterogeneous disease with different gene expression patterns. There are two major colorectal carcinogenesis pathways: conventional adenoma-carcinoma pathway and alternative serrated neoplasia pathway. Apart from the conventional pathway that is typically initiated by characteristic mutation and chromosomal instability, the serrated neoplasia pathway is mainly characterized by mutations of or , microsatellite instability (MSI), and CpG island methylator phenotype (CIMP). Despite the malignant potential of serrated lesions, they can be easily overlooked during endoscopy screening and even in pathological assessment due to its anatomical location, morphology, and histological features. It has been shown that environmental factors especially the gut microbial composition play a key role in CRC pathogenesis. Thus, the preferential localization of serrated lesions in specific intestine areas suggest that niche-specific microbiota composition might intertwined with host genetic perturbations during the development of serrated lesions. Although serrated lesions and conventional adenomas are biologically different, most studies have focused on conventional adenomas, while the pathophysiology and role of microorganisms in the development of serrated lesions remain elusive. In this review, we discuss on the role of gut microbiota in the serrated neoplasia pathway of colorectal carcinogenesis and its specific clinical and molecular features, and summarize the potential mechanisms involved.
Topics: Adenoma; Carcinogenesis; Colorectal Neoplasms; Dysbiosis; Gastrointestinal Microbiome; Humans; Mutation; Precancerous Conditions
PubMed: 33382354
DOI: 10.1080/19490976.2020.1863135 -
Nigerian Journal of Clinical Practice Apr 2023Thyroid carcinomas are the most common malignant endocrine tumors, and various immunohistochemical markers are tested in routine practice to reduce diagnostic...
BACKGROUND
Thyroid carcinomas are the most common malignant endocrine tumors, and various immunohistochemical markers are tested in routine practice to reduce diagnostic differences, as well as to elucidate carcinogenesis and detect malignancy. Disruption of basement membranes and the extracellular matrix is an important step in tumor carcinogenesis and progression. The claudin and matrix metalloproteinase families are also thought to be effective in this process.
AIM
In this retrospective study, the comparative expression of claudin-1 and MMP-7 immunomarkers in normal tissues and thyroid neoplasia were investigated.
MATERIALS AND METHODS
Immunohistochemical staining was performed for claudin-1 and matrix metalloproteinase 7 (MMP-7) in 112 sections, including 24 follicular adenomas, 22 follicular carcinomas, 24 medullary carcinomas, 24 papillary carcinomas, and 18 single dominant nodules from thyroid lesions.
RESULTS
A significant staining difference for claudin-1 was observed in follicular carcinoma and medullary carcinoma, papillary carcinoma, and single dominant nodules compared to normal thyroid tissue. A statistically significant staining difference was observed for MMP-7 in follicular adenoma, medullary carcinoma, and papillary carcinoma compared to normal thyroid tissue.
CONCLUSIONS
These results indicate that claudin-1 and MMP-7 are important in the diagnosis, differential diagnosis, and carcinogenesis of follicular adenoma, follicular carcinoma, medullary carcinoma, papillary carcinoma, and single dominant nodules.
Topics: Humans; Thyroid Gland; Claudin-1; Carcinoma, Papillary; Matrix Metalloproteinase 7; Retrospective Studies; Thyroid Neoplasms; Adenoma; Carcinogenesis; Biomarkers, Tumor
PubMed: 37203104
DOI: 10.4103/njcp.njcp_440_22 -
Clinical and Translational... Aug 2023Patients with serrated polyposis syndrome (SPS) have an increased risk to develop colorectal cancer (CRC). Due to an abundance of serrated polyps, these CRCs are assumed...
INTRODUCTION
Patients with serrated polyposis syndrome (SPS) have an increased risk to develop colorectal cancer (CRC). Due to an abundance of serrated polyps, these CRCs are assumed to arise mainly through the serrated neoplasia pathway rather than through the classical adenoma-carcinoma pathway. We aimed to evaluate the pathogenetic routes of CRCs in patients with SPS.
METHODS
We collected endoscopy and pathology data on CRCs and polyps of patients with SPS under treatment in our center. Our primary end point was the proportion of BRAFV600E mutated CRCs, indicating serrated pathway CRCs (sCRCs). CRCs lacking BRAFV600E most likely inferred a classical adenoma-carcinoma origin (aCRCs). We assessed patient, polyp, and CRC characteristics and stratified for BRAFV600E mutation status.
RESULTS
Thirty-five patients with SPS harbored a total of 43 CRCs. Twenty-one CRCs (48.8%) carried a BRAFV600E mutation, 10 of which lacked MLH1 staining and 17 (81%) were located in the proximal colon. Twenty-two CRCs (51.1%) did not carry a BRAFV600E mutation and were MLH1 proficient. Of these 22 putatively aCRCs, 17 (77.3%) were located distally and one-third (36.4%) harbored a pathogenic KRAS or NRAS mutation. In patients with BRAFwt -CRCs, a higher ratio of the median number of conventional adenomas versus serrated polyps was found (4 vs 13) than patients with BRAFV600E -CRCs (1 vs 14).
DISCUSSION
Our study indicates that in patients with SPS, the ratio of sCRCs:aCRCs on average is 50:50. This elevated sCRC:aCRC ratio in patients with SPS, when compared with non-SPS patients, correlates well with the differences in the ratios of the numbers of sessile serrated lesions and conventional adenomas in patients with SPS and non-SPS patients, respectively.
Topics: Humans; Colonic Polyps; Colorectal Neoplasms; Adenomatous Polyposis Coli; Adenoma; Carcinoma
PubMed: 37352472
DOI: 10.14309/ctg.0000000000000611 -
BMC Gastroenterology Dec 2023Colorectal cancer (CRC) screening has been implemented in Tianjin, China since 2012. The objective was to estimate the neoplasia detection rate in a high-risk population...
PURPOSE
Colorectal cancer (CRC) screening has been implemented in Tianjin, China since 2012. The objective was to estimate the neoplasia detection rate in a high-risk population by age and sex and to investigate the potential factors associated with colorectal neoplasia.
PATIENTS AND METHODS
This study is based on data of the Tianjin CRC screening program from 2012 to 2020. Residents with a positive high-risk factors questionnaire (HRFQ) or a positive faecal immunochemical test (FIT) were identified as high-risk participants and were subsequently recommended for a free colonoscopy.
RESULTS
A total of 4,117,897 eligible participants aged 40-74 years completed both a HRFQ and FIT, and 217,164 (5.3%) of them were identified as high-risk participants. Positive rates of preliminary screening increased with age and were higher in females than in males. For 57,971 participants undertaking colonoscopy, the detection rates of nonadvanced adenoma, advanced adenoma and CRC were 37.8%, 5.7% and 1.6%, respectively. Detection rates of advanced neoplasia increased from the age of 50 and were higher in males. For nonadvanced neoplasia, a strong increase was observed in males from the age of 40 and in females from the age of 50. Male sex had a greater impact on individuals aged 40-49 than on older individuals. Several factors including current smoking, drinking, and higher body mass index (BMI) were significantly associated with the presence of neoplasia, whereas, these associations were mainly restricted to individuals aged above 50 but not those aged 40-49 years.
CONCLUSIONS
These findings support that age-specific risk stratification and sex-specific initiating ages for CRC screening should be recommended to improve the accuracy and effectiveness of current screening strategy.
Topics: Female; Humans; Male; Early Detection of Cancer; Risk Factors; Colorectal Neoplasms; Colonoscopy; Occult Blood; Adenoma; Mass Screening
PubMed: 38087194
DOI: 10.1186/s12876-023-03060-3 -
Frontiers in Endocrinology 2022Mixed pituitary TSH/GH adenomas are rare adenomas associated with acromegaly and/or thyrotoxicosis, with or without varying degrees of goiter. In this report, we show a... (Review)
Review
BACKGROUND
Mixed pituitary TSH/GH adenomas are rare adenomas associated with acromegaly and/or thyrotoxicosis, with or without varying degrees of goiter. In this report, we show a case of pituitary adenoma producing both GH and TSH simultaneously.
CASE PRESENTATION
A 27-year-old man was diagnosed with pituitary adenoma based on various symptoms and clinical findings. For further examination and treatment, he was hospitalized in our institution. It was likely that this subject had pituitary adenoma producing both GH and TSH. In brain magnetic resonance imaging, there was a giant tumor in the sellar region. After the diagnosis of mixed pituitary TSH/GH adenoma, he was treated with octreotide, then underwent tumor resection, and then received hydrocortisone acetate and levothyroxine sodium. After then, GH and IGF-1 levels were suppressed and thyroid function was normalized. Postoperative immunohistochemistry reports showed GH (+) but TSH (-), which may be insensitive to the antibody used to detect TSH or combined with other factors.
CONCLUSIONS
The diagnosis of mixed pituitary TSH/GH adenoma must be combined with clinical manifestations, immunohistochemical staining and relevant hormone levels, and genetic testing if necessary for comprehensive judgment. For patients with large adenomas, it is recommended to use somatostatin analogs to restore TH levels and control the excessive secretion of GH levels before surgery.
Topics: Male; Humans; Adult; Pituitary Neoplasms; Acromegaly; Thyrotropin; Adenoma; Hyperthyroidism
PubMed: 36619586
DOI: 10.3389/fendo.2022.1072647