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Cells Jun 2021Telomeres are aging biomarkers, as they shorten while cells undergo mitosis. The aim of this study was to evaluate whether psychiatric disorders marked by psychological...
Telomeres are aging biomarkers, as they shorten while cells undergo mitosis. The aim of this study was to evaluate whether psychiatric disorders marked by psychological distress lead to alterations to telomere length (TL), corroborating the hypothesis that mental disorders might have a deeper impact on our physiology and aging than it was previously thought. A systematic search of the literature using MeSH descriptors of psychological distress ("Traumatic Stress Disorder" or "Anxiety Disorder" or "depression") and telomere length ("cellular senescence", "oxidative stress" and "telomere") was conducted on PubMed, Cochrane Library and ScienceDirect databases. A total of 56 studies (113,699 patients) measured the TL from individuals diagnosed with anxiety, depression and posttraumatic disorders and compared them with those from healthy subjects. Overall, TL negatively associates with distress-related mental disorders. The possible underlying molecular mechanisms that underly psychiatric diseases to telomere shortening include oxidative stress, inflammation and mitochondrial dysfunction linking. It is still unclear whether psychological distress is either a cause or a consequence of telomere shortening.
Topics: Humans; Mental Disorders; Mitochondria; Oxidative Stress; Telomere; Telomere Shortening
PubMed: 34200513
DOI: 10.3390/cells10061423 -
APMIS : Acta Pathologica,... Apr 2021We aimed to assess whether the presence of atypical mitotic figures (AMF) in smooth muscle tumors of uncertain malignant potential (STUMP) of the uterus and uterine...
We aimed to assess whether the presence of atypical mitotic figures (AMF) in smooth muscle tumors of uncertain malignant potential (STUMP) of the uterus and uterine adnexa is associated with increased risk of recurrence, and the association of AMF with the Stanford criteria, that is, significant cytologic atypia, mitotic index ≥ 10/10HPF, and coagulative tumor cell necrosis (CTCN). A systematic review was performed to identify all studies reporting the presence of AMF and oncologic outcomes in STUMP series. Fisher's exact test was used to assess the association of AMF with the three Stanford parameters. Kaplan-Meier and Cox regression survival analyses with hazard ratio (HR) calculation were performed to assess the association between AMF and STUMP recurrence. A p-value < 0.05 was considered significant. Five studies with 80 STUMPs were included, out of which 23.8% had AMF. AMF were significantly associated with the presence of significant atypia (p = 0.023), but not with the presence of a mitotic index ≥ 10/10HPF (p = 0.769), CTCN (p = 1), or more than one Stanford parameter (p = 0.171). AMF was not significantly associated with the risk of STUMP recurrence at both univariate (HR = 0.366; p = 0.188) and multivariate analyses (HR = 0.528; p = 0.463). In STUMP of the uterus and uterine adnexa, AMF are more common in the case of significant cytologic atypia, but do not seem to increase the risk of recurrence. Further studies are necessary in this regard.
Topics: Adnexal Diseases; Female; Humans; Leiomyoma; Mitosis; Prognosis; Uterine Neoplasms
PubMed: 33445214
DOI: 10.1111/apm.13114 -
International Journal of Gynecological... Sep 2021Cellular fibromas represent ~10% of ovarian fibromas. Mitotically active cellular fibromas show mild nuclear atypia but ≥4 mitoses/10 high-power fields: the clinical...
Cellular fibromas represent ~10% of ovarian fibromas. Mitotically active cellular fibromas show mild nuclear atypia but ≥4 mitoses/10 high-power fields: the clinical course is usually uneventful but literature review is lacking. A 34-yr-old woman underwent left oophorectomy for a 9-cm ovarian mitotically active cellular fibroma at another hospital. The tumor was cellular (spindle cells in fascicular and storiform patterns) revealing mild atypia and 4 nonatypical mitoses/10 high-power fields without necrotic areas. After 16 yr, the tumor recurred as a 5-cm peritoneal nodule on the anterior sigmoid wall near the sigmoid-rectal junction. Frozen section revealed a spindle cell tumor invading the intestinal tunica muscularis propria: a gastrointestinal stromal tumor was favored as previous history was unavailable at that time. Intestinal resection was performed: no residual tumor was found. The patient was followed-up for 8 yr without further recurrences. The peritoneal nodule showed 2 mitoses/10 high-power fields and pericellular reticulin staining. The tumor was variably positive for vimentin/bcl-2/melan-A/CD56/ER/PR/α-inhibin/CD10/calretinin, focally positive for desmin, negative for pan-cytokeratin/actin/EMA/CD34/HMB45/CD117/CD99/S100/synaptophysin. The Ki67-index was ~9%. To our systematic literature review, 7 additional recurrent cases were reported. We describe a mitotically active cellular fibroma recurring after the longest interval of time. Extensive sampling of difficult cases should exclude malignant areas. Moderate nuclear atypia, tumor rupture, adhesions to pelvic/abdominal organs, infarction with extraovarian involvement, and incomplete excision may lead to relapse but there are conflicting data: prolonged follow-up can be suggested in these cases.
Topics: Adult; Biomarkers, Tumor; Diagnosis, Differential; Female; Fibroma; Humans; Inhibins; Keratins; Neoplasm Recurrence, Local; Ovarian Neoplasms; Ovary; Synaptophysin; Vimentin
PubMed: 33252401
DOI: 10.1097/PGP.0000000000000731 -
Virchows Archiv : An International... Apr 2021Myoid gonadal stromal tumor represents a rare testicular neoplasm displaying smooth muscular and gonadal stromal differentiation. This entity has very few cases reported...
Myoid gonadal stromal tumor represents a rare testicular neoplasm displaying smooth muscular and gonadal stromal differentiation. This entity has very few cases reported in the literature that describe heterogeneous clinical and pathological characteristics. Bayesian statistics provides a useful framework to combine information from diverse sources. We here presented a case series-the largest so far reported-of myoid gonadal stromal tumor (4 cases) with extensive morphologic, immunohistochemical, and molecular characterization, performed a systematic review of the literature (that identified 9 papers), and used a Bayesian data analysis to understand the characteristics of this disease. Our study collectively described 16 cases. This neoplasm is mainly found in adults (mean age about 40 years) and often has a size of about 3 cm. By morphology, the tumor can infiltrate testicular tubules and is composed of spindle cells; few mitoses can be seen (usually 2/10 HPF). Neoplastic cells are diffusely positive with α-smooth muscle actin with a tram-track staining pattern. S100 protein, FOXL2, and SF1 are also characteristically positive. Moreover, this neoplasm can display epithelial differentiation, in about half of the cases. In conclusion, we foresee the use of this statistical approach in pathology: our analysis allowed a more precise description of this rare entity.
Topics: Adult; Bayes Theorem; Biomarkers, Tumor; Humans; Immunohistochemistry; Male; Middle Aged; Sex Cord-Gonadal Stromal Tumors; Testicular Neoplasms
PubMed: 33140129
DOI: 10.1007/s00428-020-02957-8 -
Journal of Pineal Research Nov 2020Melatonin is a ubiquitous molecule with a broad spectrum of functions including widespread anti-cancer activities. Identifying how melatonin intervenes in complex... (Meta-Analysis)
Meta-Analysis
Melatonin is a ubiquitous molecule with a broad spectrum of functions including widespread anti-cancer activities. Identifying how melatonin intervenes in complex molecular signaling at the gene level is essential to guide proper therapies. Using meta-analysis approach, herein we examined the role of melatonin in regulating the expression of 46 microRNAs (miRNAs) and their target genes in breast, oral, gastric, colorectal, and prostate cancers, and glioblastoma. The deregulated miRNA-associated target genes revealed their involvement in the regulation of cellular proliferation, differentiation, apoptosis, senescence, and autophagy. Melatonin changes the expression of miRNA-associated genes in breast, gastric, and oral cancers. These genes are associated with cellular senescence, the hedgehog signaling pathway, cell proliferation, p53 signaling, and the hippo signaling pathway. Conversely, colorectal and prostate cancers as well as glioblastoma and oral carcinoma present a clear pattern of less pronounced changes in the expression of miRNA-associated genes. Most notably, colorectal cancer displayed a unique molecular change in response to melatonin. Considering breast cancer network complexity, we compared the genes found during the meta-analysis with RNA-Seq data from breast cancer-bearing mice treated with melatonin. Mechanistically, melatonin upregulated genes associated with immune responses and apoptotic processes, whereas it downregulated genes involved in cellular aggressiveness/metastasis (eg, mitosis, telomerase activity, and angiogenesis). We further characterized the expression profile of our gene subsets with human breast cancer and found eight upregulated genes and 16 downregulated genes that were appositively correlated with melatonin. Our results pose a multi-dimension network of tumor-associated genes regulated by miRNAs potentially targeted by melatonin.
Topics: Animals; Gene Expression Regulation, Neoplastic; Humans; Melatonin; MicroRNAs; Neoplasms; RNA, Neoplasm
PubMed: 32910542
DOI: 10.1111/jpi.12693 -
Zhonghua Bing Li Xue Za Zhi = Chinese... Aug 2020To investigate the clinicopathological features, diagnosis, differential diagnosis, and molecular alterations of malignant gastrointestinal neuroectodermal tumor...
To investigate the clinicopathological features, diagnosis, differential diagnosis, and molecular alterations of malignant gastrointestinal neuroectodermal tumor (MGNET). Four cases of MGNET were collected at Fujian Provincial Hospital, from July 2013 to January 2019. H&E and immunohistochemical staining were retrospectively evaluated, together with genetic mutation analysis of EWSR1. The relevant literature was systematically reviewed. There were two male and two female patients, with an age range of 34-81 (median 57) years. Tumor sizes ranged from 5-9 (median 6.8) cm. Microscopy showed diffuse and flaky growth of tumor cells, some of which were small and round. The tumor cells were arranged in solid, flaky, nested or pseudoadenoid patterns. The tumor cells were epithelioid, oval, short spindled, or small, with round or oval nuclei. The cytoplasm was eosinophilic or clear. Osteoclast-like multinucleated giant cells were scattered focally. Mitosis was about (2-10)/10 HPF. Immunohistochemically, the tumor cells were positive for S-100 protein (4/4), SOX10 (4/4), Syn (2/4), INI1 (4/4), H3K27Me3 (4/4) and vimentin (4/4). Ki-67 index was 15%-90%. Gene mutation detection confirmed EWSR1 mutation in all four cases, and C-KIT/PDGFRα genes were not mutated in two cases. MGNET is a rare high grade malignant soft tissue tumor. The diagnosis is based on clinicopathological, immunophenotypic, and molecular pathology features. The primary treatment for MGNET is complete surgical excision and chemotherapy; the prognosis is poor.
Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Female; Gastrointestinal Neoplasms; Humans; Immunohistochemistry; Male; Middle Aged; Neuroectodermal Tumors; Retrospective Studies; S100 Proteins
PubMed: 32746550
DOI: 10.3760/cma.j.cn112151-20191204-00780 -
Frontiers in Oncology 2020Aurora kinase A (AURKA) is a cell cycle regulatory serine/threonine kinase that promotes cell cycle progression. It plays an important role in regulating the transition...
Aurora kinase A (AURKA) is a cell cycle regulatory serine/threonine kinase that promotes cell cycle progression. It plays an important role in regulating the transition from G2 to M phase during mitosis. The association between the AURKA rs2273535 T>A polymorphism and cancer risk has been investigated, but the results remain inconsistent. To get a more accurate conclusion, we conducted a comprehensive meta-analysis of 36 case-control studies, involving 22,884 cancer cases and 30,497 healthy controls. Crude odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to determine the association of interest. Pooled analysis indicated that the AURKA rs2273535 T>A polymorphism increased the overall risk of cancer (homozygous: OR = 1.17, 95% CI = 1.04-1.33; recessive: OR = 1.15, 95% CI = 1.05-1.25; allele: OR = 1.07, 95% CI = 1.02-1.13). Stratification analysis by cancer type further showed that this polymorphism was associated with an increased breast cancer risk. This meta-analysis indicated that the AURKA rs2273535 T>A polymorphism was associated with an overall increased cancer risk, especially breast cancer. Further validation experiments are needed to strengthen our conclusion.
PubMed: 32733797
DOI: 10.3389/fonc.2020.01040 -
Cancer Cell International 2020One of the most prominent features of tumor cells is uncontrolled cell proliferation caused by an abnormal cell cycle, and the abnormal expression of cell cycle-related... (Review)
Review
One of the most prominent features of tumor cells is uncontrolled cell proliferation caused by an abnormal cell cycle, and the abnormal expression of cell cycle-related proteins gives tumor cells their invasive, metastatic, drug-resistance, and anti-apoptotic abilities. Recently, an increasing number of cell cycle-associated proteins have become the candidate biomarkers for early diagnosis of malignant tumors and potential targets for cancer therapies. As an important cell cycle regulatory protein, Cell Division Cycle 25C (CDC25C) participates in regulating G2/M progression and in mediating DNA damage repair. CDC25C is a cyclin of the specific phosphatase family that activates the cyclin B1/CDK1 complex in cells for entering mitosis and regulates G2/M progression and plays an important role in checkpoint protein regulation in case of DNA damage, which can ensure accurate DNA information transmission to the daughter cells. The regulation of CDC25C in the cell cycle is affected by multiple signaling pathways, such as cyclin B1/CDK1, PLK1/Aurora A, ATR/CHK1, ATM/CHK2, CHK2/ERK, Wee1/Myt1, p53/Pin1, and ASK1/JNK-/38. Recently, it has evident that changes in the expression of CDC25C are closely related to tumorigenesis and tumor development and can be used as a potential target for cancer treatment. This review summarizes the role of CDC25C phosphatase in regulating cell cycle. Based on the role of CDC25 family proteins in the development of tumors, it will become a hot target for a new generation of cancer treatments.
PubMed: 32518522
DOI: 10.1186/s12935-020-01304-w -
Tumori Oct 2020Primary cervical leiomyosarcomas (CLMS) constitute 21% of all cervical sarcomas. Because of their rarity, to our knowledge, fewer than 40 cases have been reported. The... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Primary cervical leiomyosarcomas (CLMS) constitute 21% of all cervical sarcomas. Because of their rarity, to our knowledge, fewer than 40 cases have been reported. The aim of this study is to evaluate the clinical and surgical-pathological features, prognosis, treatment options, and survival of primary CLMS.
METHODS
A systematic review of the medical literature was conducted to evaluate articles about primary CLMS. The literature was searched between 1959 and May 2019. On final evaluation, there were 29 articles (one consisted of 8 cases; one consisted of 3 cases) and 42 cases with the addition of our 4 cases.
RESULTS
Age (⩾48 versus ⩽47 years) (hazard ratio.HR], 4.528; 95% confidence interval.CI], 1.550-13.227; =0.006) and mitoses count (<10/10 high-power field [HPF] versus ⩾10/10 HPF) (HR, 3.865; 95% CI, 1.046-14.278; =0.043) are independent prognostic factors for recurrence and age (HR, 5.318; 95% CI, 1.671-16.920; =0.005) and hysterectomy (performed versus not performed) (HR, 4.377; 95% CI, 1.341-14.283; =0.014) are independent prognostic factors for death because of disease on multivariate analysis.
CONCLUSIONS
Information on primary CLMS is sparse and obtained from rare case reports and case series. Hysterectomy must be the first choice of treatment in these patients according to our results on multivariate analysis. The type of hysterectomy does not have an effect on oncologic outcome. Radical hysterectomy is not obligatory and more data are needed to make more accurate conclusions.
Topics: Adult; Cervix Uteri; Chemotherapy, Adjuvant; Female; Humans; Hysterectomy; Leiomyosarcoma; Middle Aged; Neoplasm Recurrence, Local; Prognosis; Radiotherapy, Adjuvant; Uterine Cervical Neoplasms
PubMed: 32403994
DOI: 10.1177/0300891620919161 -
APMIS : Acta Pathologica,... Mar 2020Intraductal carcinomas (IDCs) are rare, not well-characterized salivary gland tumors. A systematic literature review of pure IDCs (without stromal invasion) of low-grade...
Intraductal carcinomas (IDCs) are rare, not well-characterized salivary gland tumors. A systematic literature review of pure IDCs (without stromal invasion) of low-grade (LG-IDCs) or high-grade (HG-IDCs) was performed: IDCs were classified using the apocrine (AR+/S100-) vs intercalated (S100+/AR-) classification. Eighty-two LG-IDCs and 11 HG-IDCs were identified (84% parotid; 11% oral; 3% submandibular; 1% lacrimal; and 1% unknown). Out of 11 HG-IDCs, 2 HG-IDCs (18%) recurred as HG-IDC or invasive carcinoma. IDCs were classified as follows: intercalated (30%); mixed apocrine and intercalated (27%); apocrine (11%); oncocytic (6%); intercalated with focal oncocytic features (1%); and unclassifiable (25%). Double AR/S100 expressors (4%) or discrepancies between morphology and immunophenotype (9%) were found. Apocrine features and necrosis were more frequent in HG-IDCs (55%; 45%). Pleomorphism favored HG-IDCs (especially when combined with >10 mitoses/10 HPFs and/or Ki67 index >10%), being associated with apocrine areas at least in 3 HG-IDCs (27%). IDCs were typically mammaglobin+/ER-/PR-/DOG1-. No immunomarker clearly distinguished HG-IDCs from LG-IDCs. About 57% IDCs (16 LG-IDCs, 1 HG-IDC) showed RET rearrangements, including NCOA4-RET (eight intercalated and two unclassifiable IDCs) and TRIM27-RET fusions (two mixed IDCs). No ETV6, ALK-1, ROS, NTRK3, MAML2, MAML3, or PLAG1 rearrangements were identified. Complete excision and total sampling should exclude invasive areas.
Topics: Biomarkers, Tumor; Carcinoma, Intraductal, Noninfiltrating; Humans; Neoplasm Recurrence, Local; Salivary Gland Neoplasms; Salivary Glands
PubMed: 31697865
DOI: 10.1111/apm.13009