scholarly journals Mitochondrial DNA Content Varies with Pathological Characteristics of Breast Cancer

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Ren-Kui Bai ◽  
Julia Chang ◽  
Kun-Tu Yeh ◽  
Mary Ann Lou ◽  
Jyh-Feng Lu ◽  
...  

Changes in mitochondrial DNA (mtDNA) content in cancers have been reported with controversial results, probably due to small sample size and variable pathological conditions. In this study, mtDNA content in 302 breast tumor/surrounding normal tissue pairs were evaluated and correlated with the clinico-pathological characteristics of tumors. Overall, mtDNA content in tumor tissues is significantly lower than that in the surrounding normal tissues,P<0.00001. MtDNA content in tumor tissues decreased with increasing tumor size. However, when the tumor is very large (>50 cm3), mtDNA content started to increase. Similarly, mtDNA content decreased from grades 0 and I to grade II tumors, but increased from grade II to grade III tumors. Tumors with somatic mtDNA alterations in coding region have significantly higher mtDNA content than tumors without somatic mtDNA alterations (P<0.001). Tumors with somatic mtDNA alterations in the D-Loop region have significantly lower mtDNA content (P<0.001). Patients with both low and high mtDNA content in tumor tissue have significantly higher hazard of death than patients with median levels of mtDNA content. mtDNA content in tumor tissues change with tumor size, grade, and ER/PR status; significant deviation from the median level of mtDNA content is associated with poor survival.

2019 ◽  
Vol 16 (2) ◽  
pp. 148-155
Author(s):  
Asma Tariq ◽  
Rana Muhammad Mateen ◽  
Iram Fatima ◽  
Muhammad Waheed Akhtar

Objective: The aim of the present study was to build protein profiles of untreated breast cancer patients of invasive ductal carcinoma grade II at tissue level in Pakistani population and to compare 2-D profiles of breast tumor tissues with matched normal tissues in order to evaluate for variations of proteins among them. Materials & Methods: Breast tissue profiles were made after polytron tissue lysis and rehydrated proteins were further characterized by using two-dimensional gel electrophoresis. On the basis of isoelectric point (pI) and molecular weight, proteins were identified by online tool named Siena 2-D database and their identification was further confirmed by using MALDI-TOF. Results: Among identified spots, 10 proteins were found to be differentially expressed i.e.; COX5A, THIO, TCTP, HPT, SODC, PPIA, calreticulin (CRT), HBB, albumin and serotransferrin. For further investigation, CRT was selected. The level of CRT in tumors was found to be significantly higher than in normal group (p < 0.05). The increased expression of CRT level in tumor was statistically significant (p = 0.010) at a 95% confidence level (p < 0.05) as analyzed by Mann-Whitney. CRT was found distinctly expressed in high amount in tumor tissue as compared to their matched normal tissues. Conclusion: It has been concluded that CRT expression could discriminate between normal tissue and tumor tissue so it might serve as a possible candidate for future studies in cancer diagnostic markers.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A632-A633
Author(s):  
Mihail Voica ◽  
Maryam Tetlay ◽  
Diane V Thompson ◽  
Farhad Hasan

Abstract Background: Hypogonadism is the most prevalent deficiency in male patients with prolactinomas (PrL). The recovery rates of hypogonadism (HGo) following treatment of PrL is variable and can be as high as 62%. In this study we aimed to identify predictors of HGo recovery in mean with PrL. We hypothesized that younger and leaner men and smaller tumor size predict HGo recovery after successful PrL treatment. We also hypothesized that higher baseline serum T predicts HGo recovery. Methods: We conducted a retrospective review of the electronic medical records of adult males with a diagnosis of hyperprolactinemia or PrL who were treated at Allegheny Health Network (Pittsburgh, PA) between January 1, 2016 and December 31, 2019. Serum prolactin and testosterone (T) levels, and pituitary tumor size (microadenoma &lt;10mm, macroadenoma 10-39mm, or giant adenoma ≥ 40 mm) on MRI scan at diagnosis and up to 2 years follow up were analyzed. HGo was defined as serum T below reference range at diagnosis. HGo recovery was defined as total T in the reference range within 2 years from PrL treatment onset in the absence of T replacement. Results: We screened 215 male patients who met initial search criteria. Of the 37 subjects who met eligibility criteria, 26 had HGo while 11 had normal serum T (Fig 1). Mean age of men with HGo was 44.6 ± 13.7 years (range 21 – 64). Median serum prolactin at diagnosis was 283.5 ng/mL (range 31-14,830), and mean serum T was 167.07 ± 61.12 ng/dL. Median tumor (max) diameter was 17.5 mm (range 4-81mm). Of the included 26 patients 20 (77%) achieved normal prolactin with therapy after a median of 5 months. Only 10 of the 26 men with HGo (38.5%) attained recovery of HGo following treatment of PrL, and the mean time to recovery was 8.8 ± 6.9 months. HGo recovery was predictably more common in persons with microadenoma (n=6) while none of patients with giant Prl achieved HGo recovery. Baseline serum prolactin and T levels and baseline tumor size predicted subsequent HGo recovery, while age did not. Baseline serum prolactin was lower in men whose HGo recovered (median = 105 ng/mL, IQR = 202) than in men who did not (median = 931 ng/mL, IQR = 3714); p = 0.014. Baseline serum T was higher in men who attained HGo recovery (173.2 ± 59.6) than in men who failed to do so (103.1 ± 85.9); p = 0.03. Mean tumor size was significantly smaller in men who attained HGo recovery (max diam: 9.8 ± 5.5 mm) than in men who did not (31.8 ± 20.3 mm); p = .003. There were no statistically significant differences between men categorized by remission status with respect to age (p = .367) nor weight at the time of diagnosis (p = .591). Conclusion: In this retrospective study of 26 males with PrL and low T at presentation, 38.5% achieved HGo recovery. Lower baseline serum prolactin, smaller tumor size and higher baseline T predicted recovery of HGo, while presenting age and weight did not. This study was limited by its retrospective nature and small sample size.


2021 ◽  
Author(s):  
Yuri Nishikawa ◽  
Takafumi Ishida

AbstractThe peopling of mainland Japan and Okinawa has been gradually unveiled in the recent years, but previous anthropological studies dealing people in the Amami islands, located between mainland Japan and Okinawa, were less informative because of the lack of genetic data. In this study, we collected DNAs from 104 subjects in two of the Amami islands, Amami-Oshima island and Kikai island, and analyzed the D-loop region of mtDNA, four Y-STRs and four autosomal nonsynonymous SNPs to clarify the genetic structure of the Amami islanders comparing with peoples in Okinawa, mainland Japan and other regions in East Asia. We found that the Amami islanders showed genetically intermediate position between mainland Japan and Okinawa in mtDNA and Y-STR. However, the frequencies of several autosomal SNPs in the Amami islanders indicated significant difference from mainland Japanese, and it may be due to the gene flow from Okinawa but not natural selection. Furthermore, extremely high or low frequencies of several alleles implied the existence of founder effect in Kikai islanders. It should be noted that there is room for the interpretation of the results because of the small sample size and number of alleles in the present study, and geographically broad and detailed samplings and genome-wide analyses are awaited.


2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
M. G. Joseph ◽  
A. Shibani ◽  
N. Panjwani ◽  
A. Arab ◽  
J. Shepherd ◽  
...  

Background. Evaluation of Ki-67 index in lung carcinoid tumors (LCTs) has been of interest in order to identify high risk subsets. Our objectives are (1) to evaluate the usefulness of Ki-67 index, mitoses, and tumor size in predicting metastasis and (2) to compare the Manual Conventional Method (MCM) and the Computer Assisted Image Analysis Method (CIAM) for Ki-67 calculation. Methods. We studied 48 patients with LCTs from two academic centres in Canada. For Ki-67 calculation, digital images of 5000 cells were counted using an image processing software and 2000 cells by MCM. Mitoses/10 HPF was counted. Results. We had 37 typical carcinoids (TCs) and 11 atypical carcinoids (ACs). 7/48 patients developed metastasis. There was a positive relationship between metastasis and carcinoid type (P=0.039) and metastasis and mitoses (≥2) (P=0.017). Although not statistically significant, the mean Ki-67 index for ACs was higher than for TCs (0.95% versus 0.72%, CIAM, P=0.299). Similarly, although not statistically significant, the mean Ki-67 index for metastatic group (MG) was higher than for nonmetastatic group (NMG) (1.01% versus 0.71% by CIAM, P=0.281). However when Ki-67 index data was categorized at various levels, there is suggestion of a useful cutoff (≥0.50%) to predict metastasis (P=0.106, CIAM). A significantly higher proportion of patients with mitosis ≥2 and Ki-67 index ≥0.50% had metastasis (P=0.033) compared to other patients. Similarly patients with tumor size ≥3 cm and Ki-67 ≥0.50% had a greater percentage of metastases than others (P=0.039). Although there was a strong correlation between two (MCM versus CIAM) counting methods (r=0.929, P=0.001), overall the calculated Ki-67 index was slightly higher by MCM (range 0 to 6.4, mean 1.5) compared to CIAM (range 0 to 2.9, mean 0.75). Conclusion. This study confirms that mitoses ≥2 is a powerful predictor of metastasis in LCTs. Although this is a small sample size, there is suggestion that analysis of Ki-67 index along with mitoses and tumor size may be a useful adjunct for predicting metastasis in LCTs.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
A M Metwalley ◽  
A Hellani ◽  
S Esteves ◽  
A El-Damen ◽  
A Abde. Razik ◽  
...  

Abstract Study question Is mitochondrial DNA viability ratio of day–4 biopsied embryos associated with embryo implantation potential? Summary answer The mitochondrial DNA viability ratio is significantly higher in embryos that implant. The score might help to select euploid embryos for single embryo transfer. What is known already Embryo euploidy is a critical factor for successful pregnancy outcomes. However, transfer of euploid embryos does not invariably result in implantation, thus indicating that other factors may play a role. Metabolic rates and adenosine triphosphate content vary significantly in oocytes and embryos and might affect embryo viability. Embryo function, indirectly measured by mitochondrial DNA viability ratio (mtV) has emerged as a potential quantitative biomarker for embryonic selection before the transfer, but clinical data remains limited. The purpose of this study is to characterize and compare mtV in euploidy day 4 embryos. Study design, size, duration Retrospective cohort study carried out between Jan. 2017 to Jan. 2020, involving 75 infertile couples undergoing IVF-ICSI with PGT-A and single embryo transfer (SET) of day 4 euploid embryos. Participants/materials, setting, methods We compared the mtV ratios of 34 non-pregnant patients with those of 41 patients who achieved clinical pregnancy after SET. The mtV ratio was obtained from a cohort of 75 euploidy embryos. The embryos were biopsied 80–85 hours post–ICSI and subjected to next-generation sequencing (NGS). The mtV was determined using Multiple of Mean (MoM) values, obtained by dividing the mtV ratio of individual embryos by the mean mtV value of all implanted embryos. Main results and the role of chance The mean mtV ratio (1.51; 95% confidence interval [CI] 1.25–1.77) of non-pregnant patients was significantly lower than those of pregnancy counterparts (2.5; 95% CI 1.82–2.68; p &lt; 0.01). At a 0.5 MoM cutoff, the sensitivity and specificity of mtV ratio to discriminate between implanted embryos versus non-implanted embryos were 35.3% and 78.2%, respectively., with a positive predictive value (PPV) of 41.4%. Limitations, reasons for caution Our study is limited by the small sample size and lack of stratification by causes of female/male infertility. Endometrial receptivity issues, which could have contributed to implantation failure, was not evaluated. Wider implications of the findings: Assessment of mtV ratio could provide additional prognostic information for selecting euploid embryos for transfer in SET programs. Further research is warranted to establish the clinical utility of routine application of mtV evaluation in PGT programs. Trial registration number N/A


2021 ◽  
Vol 8 ◽  
Author(s):  
Sarita Kumari ◽  
Mohit Arora ◽  
Jay Singh ◽  
Lokesh K. Kadian ◽  
Rajni Yadav ◽  
...  

Hepatocellular carcinoma (HCC) is an aggressive gastrointestinal malignancy with a high rate of mortality. Multiple studies have individually recognized members of RAP gene family as critical regulators of tumor progression in several cancers, including hepatocellular carcinoma. These studies suffer numerous limitations including a small sample size and lack of analysis of various clinicopathological and molecular features. In the current study, we utilized authoritative multi-omics databases to determine the association of RAP gene family expression and detailed molecular and clinicopathological features in hepatocellular carcinoma (HCC). All five RAP genes were observed to harbor dysregulated expression in HCC compared to normal liver tissues. RAP2A exhibited strongest ability to differentiate tumors from the normal tissues. RAP2A expression was associated with progressive tumor grade, TP53 and CTNNB1 mutation status. Additionally, RAP2A expression was associated with the alteration of its copy numbers and DNA methylation. RAP2A also emerged as an independent marker for patient prognosis. Further, pathway analysis revealed that RAP2A expression is correlated with tumor-infiltrating immune cell composition and oncogenic molecular pathways, such as cell cycle and cellular metabolism.


2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Zhen Liu ◽  
Zhi-pan Hong ◽  
Shu-xue Xi

Human Runt-associated transcription factor 3 (RUNX3) plays an important role in the development and progression of endometrial cancer (EC). However, the clinical and pathological significance of RUNX3 in EC needs to be further studied. In order to clarify the clinical and pathological significance of RUNX3, a systematic review and meta-analysis was conducted in EC patients. Keywords RUNX3, endometrial cancer, and uterine cancer were searched in Cochrane Library, Web of Knowledge, PubMed, CBM, MEDLINE, and Chinese CNKI database for data up to Dec 31, 2018. References, abstracts, and meeting proceedings were manually searched in supplementary. Outcomes were various clinical and pathological features. The two reviewers performed the literature searching, data extracting, and method assessing independently. Meta-analysis was performed by RevMan5.3.0. A total of 563 EC patients were enrolled from eight studies. Meta-analysis results showed that the expression of RUNX3 has significant differences in these comparisons: lymph node (LN) metastasis vs. non-LN metastasis ( P = 0.26 ), EC tissues vs. normal tissues ( P < 0.00001 ), clinical stages I/II vs. II/IV ( P < 0.00001 ), muscular infiltration < 1 / 2 vs. muscular infiltration ≥ 1 / 2 ( P < 0.00001 ), and G1 vs. G2/G3 ( P < 0.00001 ). The decreasing expression of RUNX3 is associated with poor TNM stage and muscular infiltration. It is indicated that RUNX3 was involved in the suppression effect of EC. However, further multicenter randomized controlled trials are needed considering the small sample size of the included trials.


Author(s):  
Conly L. Rieder ◽  
S. Bowser ◽  
R. Nowogrodzki ◽  
K. Ross ◽  
G. Sluder

Eggs have long been a favorite material for studying the mechanism of karyokinesis in-vivo and in-vitro. They can be obtained in great numbers and, when fertilized, divide synchronously over many cell cycles. However, they are not considered to be a practical system for ultrastructural studies on the mitotic apparatus (MA) for several reasons, the most obvious of which is that sectioning them is a formidable task: over 1000 ultra-thin sections need to be cut from a single 80-100 μm diameter egg and of these sections only a small percentage will contain the area or structure of interest. Thus it is difficult and time consuming to obtain reliable ultrastructural data concerning the MA of eggs; and when it is obtained it is necessarily based on a small sample size.We have recently developed a procedure which will facilitate many studies concerned with the ultrastructure of the MA in eggs. It is based on the availability of biological HVEM's and on the observation that 0.25 μm thick serial sections can be screened at high resolution for content (after mounting on slot grids and staining with uranyl and lead) by phase contrast light microscopy (LM; Figs 1-2).


Crisis ◽  
2020 ◽  
pp. 1-5
Author(s):  
Ruthmarie Hernández-Torres ◽  
Paola Carminelli-Corretjer ◽  
Nelmit Tollinchi-Natali ◽  
Ernesto Rosario-Hernández ◽  
Yovanska Duarté-Vélez ◽  
...  

Abstract. Background: Suicide is a leading cause of death among Spanish-speaking individuals. Suicide stigma can be a risk factor for suicide. A widely used measure is the Stigma of Suicide Scale-Short Form (SOSS-SF; Batterham, Calear, & Christensen, 2013 ). Although the SOSS-SF has established psychometric properties and factor structure in other languages and cultural contexts, no evidence is available from Spanish-speaking populations. Aim: This study aims to validate a Spanish translation of the SOSS-SF among a sample of Spanish-speaking healthcare students ( N = 277). Method: We implemented a cross-sectional design with quantitative techniques. Results: Following a structural equation modeling approach, a confirmatory factor analysis (CFA) supported the three-factor model proposed by Batterham and colleagues (2013) . Limitations: The study was limited by the small sample size and recruitment by availability. Conclusion: Findings suggest that the Spanish version of the SOSS-SF is a valid and reliable tool with which to examine suicide stigma among Spanish-speaking populations.


Crisis ◽  
2020 ◽  
pp. 1-7
Author(s):  
Brooke A. Ammerman ◽  
Sarah P. Carter ◽  
Heather M. Gebhardt ◽  
Jonathan Buchholz ◽  
Mark A. Reger

Abstract. Background: Patient disclosure of prior suicidal behaviors is critical for effectively managing suicide risk; however, many attempts go undisclosed. Aims: The current study explored how responses following a suicide attempt disclosure may relate to help-seeking outcomes. Method: Participants included 37 veterans with a previous suicide attempt receiving inpatient psychiatric treatment. Veterans reported on their most and least helpful experiences disclosing their suicide attempt to others. Results: Veterans disclosed their suicide attempt to approximately eight individuals. Mental health professionals were the most cited recipient of their most helpful disclosure; romantic partners were the most common recipient of their least helpful disclosures. Positive reactions within the context of the least helpful disclosure experience were positively associated with a sense of connection with the disclosure recipient. Positive reactions within the most helpful disclosure experience were positively associated with the likelihood of future disclosure. No reactions were associated with having sought professional care or likelihood of seeking professional care. Limitations: The results are considered preliminary due to the small sample size. Conclusion: Findings suggest that while positive reactions may influence suicide attempt disclosure experiences broadly, additional research is needed to clarify factors that drive the decision to disclose a suicide attempt to a professional.


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