scholarly journals Breaking the scale: how disrupting the karyoplasmic ratio gives cancer cells an advantage for metastatic invasion

2017 ◽  
Vol 45 (6) ◽  
pp. 1333-1344
Author(s):  
Andrea Rizzotto ◽  
Eric C. Schirmer
Keyword(s):  
Breast Cancer ◽  
Lung Cancer ◽  
Cancer Cells ◽  
Nuclear Size ◽  
Nuclear Morphology ◽  
Metastatic Tumors ◽  
Size Regulation ◽  
Diagnosis And Prognosis ◽  
Ploidy Changes ◽  
Tumor Types

Nuclear size normally scales with the size of the cell, but in cancer this ‘karyoplasmic ratio’ is disrupted. This is particularly so in more metastatic tumors where changes in the karyoplasmic ratio are used in both diagnosis and prognosis for several tumor types. However, the direction of nuclear size changes differs for particular tumor types: for example in breast cancer, larger nuclear size correlates with increased metastasis, while for lung cancer smaller nuclear size correlates with increased metastasis. Thus, there must be tissue-specific drivers of the nuclear size changes, but proteins thus far linked to nuclear size regulation are widely expressed. Notably, for these tumor types, ploidy changes have been excluded as the basis for nuclear size changes, and so, the increased metastasis is more likely to have a basis in the nuclear morphology change itself. We review what is known about nuclear size regulation and postulate how such nuclear size changes can increase metastasis and why the directionality can differ for particular tumor types.

scholarly journals Tumor Cell Associated Hyaluronan-CD44 Signaling Promotes Pro-Tumor Inflammation in Breast Cancer

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1325 ◽  
Author(s):  
Patrice M. Witschen ◽  
Thomas S. Chaffee ◽  
Nicholas J. Brady ◽  
Danielle N. Huggins ◽  
Todd P. Knutson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Chronic Wound ◽  
Gene Signature ◽  
Tumor Formation ◽  
Human Breast ◽  
Inflammatory Microenvironment ◽  
Tumor Types

Cancer has been conceptualized as a chronic wound with a predominance of tumor promoting inflammation. Given the accumulating evidence that the microenvironment supports tumor growth, we investigated hyaluronan (HA)-CD44 interactions within breast cancer cells, to determine whether this axis directly impacts the formation of an inflammatory microenvironment. Our results demonstrate that breast cancer cells synthesize and fragment HA and express CD44 on the cell surface. Using RNA sequencing approaches, we found that loss of CD44 in breast cancer cells altered the expression of cytokine-related genes. Specifically, we found that production of the chemokine CCL2 by breast cancer cells was significantly decreased after depletion of either CD44 or HA. In vivo, we found that CD44 deletion in breast cancer cells resulted in a delay in tumor formation and localized progression. This finding was accompanied by a decrease in infiltrating CD206+ macrophages, which are typically associated with tumor promoting functions. Importantly, our laboratory results were supported by human breast cancer patient data, where increased HAS2 expression was significantly associated with a tumor promoting inflammatory gene signature. Because high levels of HA deposition within many tumor types yields a poorer prognosis, our results emphasize that HA-CD44 interactions potentially have broad implications across multiple cancers.

scholarly journals Evaluating the Origin of the Brain Metastatic Tumors by Using DWI Parameters

2019 ◽  
Vol 6 (3) ◽  
pp. 92-97
Author(s):  
Farnoush Mousavi ◽  
Fariborz Faeghi ◽  
Hamed Javadian ◽  
Hamidreza Haghighatkhah ◽  
Saeed Oraee-Yazdani
Keyword(s):  
Breast Cancer ◽  
Lung Cancer ◽  
Brain Metastases ◽  
Diffusion Weighted Imaging ◽  
Spin Echo ◽  
Metastatic Tumors ◽  
Diffusion Weighted ◽  
Spin Echo Sequence ◽  
Adc Values ◽  
The Brain

Background: Brain metastases are the most common tumors in the human central nervous system (CNS), with an occurrence 10 times higher than primary brain tumors in adults. A radiologist usually diagnoses these tumors. Typically, magnetic resonance imaging (MRI) has been used to evaluate the status and number of metastases, the design of surgical treatment or radiotherapy, and the response to treatment. This study aimed to consider the origin of metastatic tumors of the brain using diffusionweighted imaging sequence. Methods: In this study, 95 lesions observed in 51 patients with different types of brain metastasis who analyzed with standard brain MRI protocols such as T2-weighted fast spin-echo in sagittal, coronal and axial planes and T1-weighted spin-echo sequences before and after injection of contrast enhancement and diffusion-weighted imaging. The diffusion-weighted imaging included an echoplanar spin-echo sequence with two b values (0,1000 s/mm) and calculated apparent diffusion coefficient (ADC) maps. We measured the ADC-value on normalized ADC maps and compared them with different methods. ANOVA was used to compare ADC among all groups as well as T-test for every two groups. Results: The results showed that patients with lung cancer (squamous cell carcinoma, SCC) had the lowest mean ADC (658.70*10-3 mm2 /s) and breast cancer patients with the highest mean ADC(935.52*10-3 mm2 /s). This study demonstrated that most Brain metastases had low and intermediate ADC values. The analysis showed no significant difference among all groups. However, ADC values in breast cancer and kidney and lung (adenocarcinoma) were statistically higher in comparison to other groups. There were no critical discrepancies between ADC values in brain metastases from Breast cancer and lung cancer (adenocarcinoma) and kidney. Conclusion: It seems that evaluating the origin of the brain metastatic tumors by using diffusion imaging (DWI) parameters could be helpful to prevent invasive methods like biopsies in some situations. Although it needs more studies to achieve this purpose.

scholarly journals Evaluation of Oncogene NUP37 as a Potential Novel Biomarker in Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Kangdi Li ◽  
Ting Liu
Keyword(s):  
Breast Cancer ◽  
Cell Growth ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Breast Cancer Cells ◽  
Target Therapy ◽  
Breast Cancer Patients ◽  
Hub Gene ◽  
Diagnosis And Prognosis ◽  
Potential Marker

PurposeThere is an urgent need to identify oncogenes that may be beneficial to diagnose and develop target therapy for breast cancer.MethodsBased on the GEO database, DECenter was used to screen the differentially overexpressed genes in breast cancer samples. Search Tool for the Retrieval of Interacting Genes and Cytoscape were performed to construct the PPI network to predict the hub gene. Functional and pathway enrichment were performed based on GO analysis. GEO2R, Oncomine, human tissue microarray staining, and western blot were applied to confirm the expression of NUP37. The association between NUP37 expression and prognosis in patients with breast cancer were assessed using the Kaplan–Meier plotter online tool and OncoLnc. siRNAs were used to knock down NUP37 and evaluate proliferation, migration, and stemness in breast cancer cells.ResultsWe found that 138 genes were differentially upregulated in breast cancer samples, mainly comprising components of the nucleus and involved in the cell cycle process. NUP37 was identified as a hub gene that is upregulated in breast cancer patients related to a significantly worse survival rate. Furthermore, we confirmed that the downregulation of NUP37 in breast cancer cells results in the inhibition of cell growth, migration, and stemness.ConclusionsHigh expression of NUP37 in breast cancer patients is associated with a poorer prognosis and promotion of cell growth, migration, and stemness. The multiple bioinformatics and experimental analysis help provide a comprehensive understanding of the roles of NUP37 as a potential marker for diagnosis and prognosis and as a novel therapeutic target in breast cancer.

scholarly journals Anticancer Activity of Ipomoea purpurea Leaves Extracts in Monolayer and Three-Dimensional Cell Culture

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
F. Beheshti ◽  
A. A. Shabani ◽  
M. R. Akbari Eidgahi ◽  
P. Kookhaei ◽  
M. Vazirian ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lung Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Three Dimensional ◽  
Human Lung Cancer ◽  
Phase Cell ◽  
Ipomoea Purpurea ◽  
Organic Extracts

Cancer is a leading cause of death and a vital health care challenge in the world. Hence, this work was conducted to determine the in vitro anticancer property and also the molecular mechanism of aqueous and organic extracts of Ipomoea purpurea leaves in three human cancer cell lines, including A-549 (human lung cancer), HepG-2 (human liver cancer), MDA-MB-231 (human breast cancer), and MCF-10A (breast normal cell line). In vitro cytotoxic potential of organic extracts, such as hexane, chloroform, ethyl-acetate, methanol, and aqueous extract was examined using a standard (3-(4,5-dimethylthiazole)-2,5-diphenyltetrazolium bromide) MTT method in both monolayer two-dimensional (2D) and spheroids multicellular three-dimensional (3D) cultures. The MTT assay data showed that methanol and chloroform extracts of I. purpurea leaves had the antiproliferative effect on lung and breast cancer cells with IC50 of 53.62 ± 0.07 and 124.5 ± 0.01 µg/mL, respectively. The results of further examinations, such as dual acridine orange/ethidium bromide, Annexin V-FITC/PI, and caspase-3 colorimetric assay, confirmed that methanol and chloroform extracts of I. purpurea as the most potent cytotoxic extracts might contain a variety of phytochemicals, promoting apoptosis in lung and breast cancer cells. The present research findings suggested that methanolic extract of I. purpurea leaves induced S-phase cell cycle arrest and intrinsic pathway of apoptosis in A-549 lung cancer cells. The study further showed that I. purpurea could be a helpful candidate for cancer treatment.

Evaluating the Safety of Erythropoiesis-Stimulating Agents (ESAs) in Patients with Breast Cancer, Lung Cancer, and Hematologic Malignancies: A Meta-Analysis of Randomized, Controlled Trials.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3669-3669
Author(s):  
J. Glaspy ◽  
D. Henry ◽  
J. Vansteenkiste ◽  
H. Ludwig ◽  
T. Lillie ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lung Cancer ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Hematologic Malignancies ◽  
Controlled Trials ◽  
Risk Of Death ◽  
Randomized Controlled ◽  
Total Body ◽  
Tumor Types

Abstract Background: Recent clinical trial data have generated safety concerns regarding ESA use, particularly as to whether the results observed in certain patients with breast cancer, lung cancer, and hematologic malignancies are generalizable to all patients with those tumor types. It is critical that the results of these studies are appropriately integrated into the total body of evidence in order to enable balanced conclusions to be drawn. We conducted a systematic literature review to assess the safety and efficacy of ESA therapy in patients with breast cancer, lung cancer, and hematologic malignancies. Methods: The search was aligned with that conducted by the Cochrane Collaborative group (Bohlius 2006) and was therefore limited to randomized, controlled clinical trials in cancer patients that compared the use of ESAs with either observation (RBC transfusion as required) or placebo and that collected survival data (either long-term or during the study period). Results from trials were meta-analyzed using Comprehensive Meta-Analysis v 2.2 software. Heterogeneity between studies was evaluated using a chi-square test (Q). Random and fixed-effects models were used to estimate an overall odds ratio and 95% confidence interval; the inconsistency statistic, I2, is also provided. Results: For breast cancer, seven studies were identified. Meta-analysis of data from these studies indicated an overall neutral risk of death for patients receiving ESAs, despite the large contribution (weighted at about 40% of the overall result) of the BEST study results (Leyland-Jones, 2005) (Table). Five ESA-controlled lung cancer studies were identified in CIA, one in radiotherapy, and one in anemia of cancer (AOC). In each of the studies in CIA, the ESA groups had neutral survival risks relative to the control group. Meta-analysis of the CIA, radiotherapy, and AOC lung cancer data combined indicated an overall neutral risk of death for patients receiving ESAs (Table). For hematologic malignancies, eight studies were identified (one of which had no deaths). Meta-analysis indicated an overall neutral risk of death for patients receiving ESAs (Table). Conclusions: The results of some studies have suggested a detrimental effect on survival associated with ESA use in certain patients with breast, lung, and hematological malignancies. However, results do not appear to be generalizable to similarly designed, randomized controlled trials conducted in the same tumor types. Additionally, when these studies are integrated into the total body of evidence, ESAs have a neutral effect on survival in these patients.

The prevalence of KRASG12C mutations utilizing circulating tumor DNA (ctDNA) in 80,911 patients with cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3547-3547 ◽  
Author(s):  
Kyaw Thein ◽  
Kimberly Banks ◽  
Jennifer Saam ◽  
Victoria M. Raymond ◽  
Jason Roszik ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Solid Tumors ◽  
Squamous Cell ◽  
Lung Carcinoma ◽  
Cancer Type ◽  
Squamous Cell Lung Carcinoma ◽  
Cell Lung Carcinoma ◽  
Tumor Types

3547 Background: Kirsten rat sarcoma viral oncogene homolog (KRAS) is the most commonly mutated proto-oncogene identified in cancer and still remains an arduous therapeutic challenge. Recently, KRASG12C mutation has become special interest since it has now been considered potentially druggable after the introduction of covalent small-molecule KRASG12C inhibitors. Advances in next-generation sequencing (NGS) and embracing utilization of ctDNA have uncovered more genetic alterations in many cancers. We present a comprehensive analysis on the prevalence of KRASG12C mutations identified by ctDNA. Methods: We conducted a 5-year (July 2014 to June 2019) retrospective review of ctDNA NGS analysis in the Guardant360 CLIA database inclusive of treatment-naïve and previously treated patients with metastatic solid tumors. Data were retrieved from the 80,911 unique patients with ctDNA detected. Clonality and co-occurrence of cancer type were analyzed. Clonality was defined as variant allele fraction(AF) / maximum somatic AF in the sample. Results: 80,911 patients, which included more than 100 tumor histologies, were identified. 2,985 patients (3.7%) with > 40 tumor types had KRASG12C mutations identified in ctDNA. KRASG12C prevalence by cancer type were as follows: sarcomatoid lung carcinoma (13.5%), lung cancer NOS (9%), large cell lung carcinoma (9%), lung adenocarcinoma (7.4%), NSCLC (6.9%), carcinoma of unknown primary (CUP) (4.1%), lung carcinoid (4%), CRC (3.5%), squamous cell lung carcinoma (2%), small cell lung carcinoma (1.5%), pancreatic ductal adenocarcinoma (PDAC) (1.2%), cholangiocarcinoma (1.2%), bladder cancer (0.6%), ovarian cancer (0.6%) and breast cancer (0.3%). 53 additional patients with KRASG12C were identified across 24 other tumor types. The KRASG12C mutation was found to be clonal (clonality > 0.9%) in the majority of patients with lung adenocarcinoma, NSCLC, CUP, squamous cell lung carcinoma, and PDAC, compared to patients with CRC and breast cancer who had bimodal distribution of clonal and sub clonal mutations. Conclusions: To our knowledge, this is the largest analysis on the prevalence of KRASG12C mutations identified by ctDNA. Our study demonstrated the feasibility of utilizing ctDNA to identify KRASG12C mutations across solid tumors with the highest prevalence in lung cancer as previously reported in tissue. The clonality information available from ctDNA-based genotyping may provide insights into the clinical efficacy of targeting KRASG12C in different tumor types.

scholarly journals Metastatic ovarian cancer spreading into mammary ducts mimicking an in situ component of primary breast cancer: a case report

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Yurina Maeshima ◽  
Tomo Osako ◽  
Hidetomo Morizono ◽  
Mayu Yunokawa ◽  
Yumi Miyagi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Cancer Cells ◽  
Growth Pattern ◽  
Breast Tumor ◽  
Primary Breast Cancer ◽  
Serous Carcinoma ◽  
Metastatic Tumors ◽  
Primary Tumors

Abstract Background Accurate diagnosis of metastatic tumors in the breast is crucial because the therapeutic approach is essentially different from primary tumors. A key morphological feature of metastatic tumors is their lack of an in situ carcinoma component. Here, we present a unique case of metastatic ovarian carcinoma spreading into mammary ducts and mimicked an in situ component of primary carcinoma. To our knowledge, this is the second case (and the first adult case) confirming the in situ-mimicking growth pattern of a metastatic tumor using immunohistochemistry. Case presentation A 69-year-old Japanese woman was found to have a breast mass with microcalcifications. She had a known history of ovarian mixed serous and endocervical-type mucinous (seromucinous) carcinoma. Needle biopsy specimen of the breast tumor revealed adenocarcinoma displaying an in situ-looking tubular architecture in addition to invasive micropapillary and papillary architectures with psammoma bodies. From these morphological features, metastatic serous carcinoma and invasive micropapillary carcinoma of breast origin were both suspected. In immunohistochemistry, the cancer cells were immunoreactive for WT1, PAX8, and CA125, and negative for GATA3, mammaglobin, and gross cystic disease fluid protein-15. Therefore, the breast tumor was diagnosed to be metastatic ovarian serous carcinoma. The in situ-looking architecture showed the same immunophenotype, but was surrounded by myoepithelium confirmed by immunohistochemistry (e.g. p63, cytokeratin 14, CD10). Thus, the histogenesis of the in situ-like tubular foci was could be explained by the spread of metastatic ovarian cancer cells into existing mammary ducts. Conclusion Metastatic tumors may spread into mammary duct units and mimic an in situ carcinoma component of primary breast cancer. This in situ-mimicking growth pattern can be a potential pitfall in establishing a correct diagnosis of metastasis to the breast. A panel of breast-related and extramammary organ/tumor-specific immunohistochemical markers may be helpful in distinguishing metastatic tumors from primary tumors.

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