Targeting the Ribosome Biogenesis Key Molecule Fibrillarin to Avoid Chemoresistance

2019 ◽  
Vol 26 (33) ◽  
pp. 6020-6032 ◽  
Author(s):  
Btissame El Hassouni ◽  
Dzjemma Sarkisjan ◽  
J. Chris Vos ◽  
Elisa Giovannetti ◽  
Godefridus J. Peters
Keyword(s):  
Cancer Treatment ◽  
Cancer Patients ◽  
Ribosome Biogenesis ◽  
Breast Cancer Patients ◽  
Cellular Processes ◽  
Pol I ◽  
Gene Coding ◽  
Anti Cancer ◽  
Cytogenetic Band ◽  
P53 Status

Background: Inherent or acquired chemo resistance in cancer patients has been a perpetual limitation in cancer treatment. Expanding knowledge on essential cellular processes opens a new window for therapeutic targeting. Ribosome biogenesis is a process that shows potential due to its fundamental role in cell development and contribution to tumorigenesis as a result of its upregulation. Inhibiting components of ribosome biogenesis has been explored and has shown interesting results. Yet, an important key component, methyltransferase Fibrillarin (FBL), which influences both the abundance and composition of ribosomes, has not been exploited thus far. Methods: In this literature review, we describe relevant aspects of ribosome biogenesis in cancer to emphasize the potential of FBL as a therapeutic target, in order to lower the genotoxic effects of anti-cancer treatment. Results: Remarkably, the amplification of the 19q13 cytogenetic band, including the gene coding for FBL, correlated to cell viability and resistance in pancreatic cells as well as to a trend toward a shorter survival in pancreatic cancer patients. : Targeting ribosome biogenesis, more specifically compared to the secondary effects of chemotherapeutics such as 5-fluorouracil or oxaliplatin, has been achieved by compound CX-5461. The cell dependent activity of this Pol I inhibitor has been reported in ovarian cancer, melanoma and leukemia models with active or mutated p53 status, presenting a promising mechanism to evade p53 resistance. Conclusion: Targeting critical ribosome biogenesis components in order to decrease the genotoxic activity in cancer cell looks promising. Hence, we believe that targeting key protein rRNA methyltransferase FBL shows great potential, due to its pivotal role in ribosome biogenesis, its correlation to an improved survival rate at low expression in breast cancer patients and its association with p53.

scholarly journals The association between infection incidence and autoimmune diseases in breast cancer patients after anti-cancer treatment

2019 ◽  
Vol 10 (4) ◽  
pp. 829-835
Author(s):  
Chien-Chih Chen ◽  
Wei-Li Ho ◽  
Hsin-Hua Chen ◽  
Meei-Ling Sheu ◽  
Chiann-Yi Hsu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Autoimmune Diseases ◽  
Cancer Treatment ◽  
Cancer Patients ◽  
Breast Cancer Patients ◽  
Infection Incidence ◽  
Anti Cancer

scholarly journals The effects of an individualized exercise intervention on body composition in breast cancer patients undergoing treatment

2007 ◽  
Vol 125 (1) ◽  
pp. 22-28 ◽  
Author(s):  
Claudio Battaglini ◽  
Martim Bottaro ◽  
Carolyn Dennehy ◽  
Logan Rae ◽  
Edgar Shields ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Body Composition ◽  
Resistance Training ◽  
Cancer Treatment ◽  
Cancer Patients ◽  
Exercise Intervention ◽  
Exercise Group ◽  
Moderate Intensity ◽  
Control Group ◽  
Breast Cancer Patients

CONTEXT AND OBJECTIVE: Changes in metabolism have been reported in the majority of patients undergoing cancer treatment, and these are usually characterized by progressive change in body composition. The effects of aerobic exercise programs to combat the cancer and cancer treatment-related side effects, which include the negative changes in body composition, have been extensively reported in the literature. However, few resistance exercise intervention studies have hypothesized that breast cancer patients might benefit from this type of exercise. The purpose of this study was to determine whether exercise protocols that emphasize resistance training would change body composition and strength in breast cancer patients undergoing treatment. DESIGN AND SETTING: Randomized controlled trial, at the Campus Recreation Center and Rocky Mountain Cancer Rehabilitation Institute of the University of Northern Colorado, and the North Colorado Medical Center. METHODS: Twenty inactive breast cancer patients were randomly assigned to a 21-week exercise group (n = 10) or a control group (n = 10). The exercise group trained at low to moderate intensity for 60 minutes on two days/week. The primary outcome measurements included body composition (skinfold method) and muscle strength (one repetition maximum). RESULTS: Significant differences in lean body mass, body fat and strength (p = 0.004, p = 0.004, p = 0.025, respectively) were observed between the groups at the end of the study. CONCLUSION: The results suggest that exercise emphasizing resistance training promotes positive changes in body composition and strength in breast cancer patients undergoing treatment.

Can Intratumoral neutrophil lymphocyte ratio (NLR) be a prognostic biomarker in breast cancer patients?

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12573-e12573
Author(s):  
Yoshihisa Tokumaru ◽  
Masanori Oshi ◽  
Vijayashree Murthy ◽  
Eriko Katsuta ◽  
Nobuhisa Matsuhashi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Cancer Patients ◽  
Immune Cells ◽  
Breast Cancer Patients ◽  
Immune Microenvironment ◽  
High Group ◽  
Anti Cancer ◽  
Tumor Immune Microenvironment ◽  
Er Positive

e12573 Background: In breast cancer patients, it is well known that the elevation of neutrophil lymphocyte ratio (NLR) in the blood are reported to associate with poor prognosis based on the notion that neutrophils represent pro-cancer, and lymphocytes represent anti-cancer immune cells. Tumor immune microenvironment has been demonstrated to play critical roles in the outcome of breast cancer patients. However, there is scarce evidence on the clinical relevance of intratumoral NLR in breast cancer patients. In the current study, we hypothesized that intratumoral NLR high tumors are associated with worse survival particularly in TNBC that is known to have high immune cell infiltration. Methods: A total of 1904 breast cancer patients’ data from METABRIC (Molecular Taxonomy of Breast Cancer International Consortium) and analyzed. NLR was calculated by the gene expressions of CD66b (CEACAM8) and CD8 (CD8A). NLR high and low were divided by the median. Overall Survival (OS) and Disease-Free Survival were calculated utilizing Kaplan Meier method between intratumoral NLR high and low groups. xCell algorithm was used to analyze the infiltrated immune cells within the tumor immune microenvironment as we have previously published. Results: Intratumoral NLR high group was associated with worse OS in whole, ER-positive/HER2-negative, and triple negative (TN) subtypes, in agreement with the previous studies. TN subtype alone demonstrated worse DFS of NLR high group. Surprisingly, gene set enrichment analysis (GSEA) demonstrated no gene set enrichment to NLR high group, which implicates that there is no distinctive mechanism that associate with worse survival. Whereas, immune response-related gene sets significantly enriched to NLR low group in TN subtype. This enrichment was consistent in ER-positive/HER2-negative. Compared with ER-positive/HER2-negative subtype, anti-cancer immune cells such as CD4+ T cells, CD8+ T cells, M1 macrophage, and helper T helper type 1 cells were significantly infiltrated in TN patients (p < 0.001 for all genes), where M2 macrophages and neutrophils were less and regulatory T cells and T helper type 2 cells were more infiltrated in TN subtype. Furthermore, intratumoral NLR was significantly lower in TN compared with ER-positive/HER2-negative subtype (p < 0.001). These results suggest that intratumoral NLR low group is associated with better survival due to favorable tumor immune microenvironment in TN subtype rather than NLR high group has worse survival. Conclusions: Intratumoral NLR low tumor demonstrated more favorable OS and more favorable DFS in TN patients. Intratumoral NLR low breast cancer was associated with enhanced immune response and higher infiltration of anti-cancer immune cells were observed in TN subtype compared to ER-positive/HER2-negative which may contribute to the favorable outcome of in TN breast cancer.

scholarly journals The impact of COVID 19 pandemic on pattern of cancer mortality in Najran, Saudi Arabia: a single-cancer center experience

2021 ◽  
Author(s):  
Ahmed M Badheeb ◽  
Mohamed A Badheeb ◽  
Hamdi A Alhakimi
Keyword(s):  
Hepatocellular Carcinoma ◽  
Saudi Arabia ◽  
Cancer Treatment ◽  
Cancer Patients ◽  
Cancer Mortality ◽  
Cancer Center ◽  
Anti Cancer ◽  
Before And After ◽  
The Difference ◽  
The Impact

Abstract Background: The aim of this paper is to compare the patterns and determinants of cancer mortality in Najran region before and after the COVID-19 epidemics. The association between cancer mortality and each of age, sex, site of cancer, stage, and the 30-days survival rate after the last dose of chemotherapy were assessed.Materials & Methods: Adult cancer patients who died of cancer in King Khalid Hospital in Najran Saudi Arabia, were included in this retrospective observational study. We compared mortality patterns in a period of 6 months in 2020 (March to August) with the corresponding period of 2019.Results: 50 dead adult cancer patients were included, 24 in 2019 and 26 in 2020. Among them, 21% vs 42% were younger than 65 years of age; 61% vs 62% were males, for the years 2019 & 2020 respectively. The top three killers in 2019 were colorectal, gastro-esophageal cancers, and hepatocellular carcinoma, while in 2020 were colorectal, hepatocellular carcinoma, and lymphomas. About 16.7% of patients died within 30 days of receiving anti-cancer treatment in 2019 in comparison with 7.7% in 2020. The difference in the 30-days mortality after receiving anti-cancer treatment was not statistically significant between 2019 and 2020 (p = 0.329).Conclusion: The Year 2020, the time of the COVID-19pandemic, was not associated with a significant increase in short-term mortality among patients with malignancy in Najran, Saudi Arabia. Our results generally reflect the crucial role of strict preventive national measures in saving lives and warrants further exploration.

scholarly journals Probiotics for the Treatment of Docetaxel-Related Weight Gain of Breast Cancer Patients—A Single-Center, Randomized, Double-Blind, and Placebo-Controlled Trial

2021 ◽  
Vol 8 ◽  
Author(s):  
Zhang Juan ◽  
Zhang Qing ◽  
Liang Yongping ◽  
Liyuan Qian ◽  
Wei Wu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Body Weight ◽  
Weight Gain ◽  
Cancer Treatment ◽  
Cancer Patients ◽  
Body Fat ◽  
Breast Cancer Treatment ◽  
Body Fat Percentage ◽  
Breast Cancer Patients ◽  
Fat Percentage

Background: Docetaxel is an important chemotherapy-agent for breast cancer treatment. One of its side-effects is weight gain, which increases the all-cause mortality rate. Considering gut microbiota is one important factor for weight regulation, we hypothesized that probiotics could be potentially used to reduce the docetaxel-related weight gain in breast cancer patients.Methods: From 10/8/2018 to 10/17/2019, 100 breast cancer (Stage I-III) patients underwent four cycles of docetaxel-based chemotherapy were enrolled and randomly assigned to receive probiotics (Bifidobacterium longum, Lactobacillus acidophilus, and Enterococcus faecalis) or placebo (supplementary material of the probiotics capsule) treatment for 84 days with three capsules per time, twice/day. The primary outcome: the changes in body weight and body-fat percentage of the patients were measured by a designated physician using a fat analyzer, and the secondary outcomes: the fasting insulin, plasma glucose, and lipids were directly obtained from the Hospital Information System (HIS); The metabolites were measured using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS); The fecal microbiome was analyzed using bacterial 16S ribosomal RNA (rRNA) gene sequence. All indicators were measured 1 day before the first cycle of docetaxel-based chemotherapy and 21 days after the last cycle of docetaxel-based chemotherapy.Results: Compared with the placebo group, the probiotic group showed significantly smaller changes in body weight (Mean [SD] 0.77 [2.58] vs. 2.70 [3.08], P = 0.03), body-fat percentage (Mean [SD] 0.04 [1.14] vs. 3.86 [11.09], P = 0.02), and low density lipoprotein (LDL) (Mean [SD]−0.05[0.68] vs. 0.39 [0.58], P = 0.002). Moreover, five of the 340 detected plasma metabolites showed significant differences between the two groups. The change of biliverdin dihydrochloride (B = −0.724, P = 0.02) was inverse correlated with weight gain. One strain of the phylum and three strains of the genus were detected to be significantly different between the two groups. Also, the changes of Bacteroides (B = −0.917, P &lt; 0.001) and Anaerostipes (B = −0.894, P &lt; 0.001) were inverse correlated with the change of LDL.Conclusions: Probiotics supplement during docetaxel-based chemotherapy for breast cancer treatment may help to reduce the increase in body weight, body-fat percentage, plasma LDL, and minimize the metabolic changes and gut dysbacteriosis.Clinical Trial Registration:http://www.chictr.org.cn/showproj.aspx?proj=24294, ChiCTR-INQ-17014181.

scholarly journals Anti-Cancer Activities of Tea Epigallocatechin-3-Gallate in Breast Cancer Patients under Radiotherapy

2012 ◽  
Vol 12 (2) ◽  
pp. 163-176 ◽  
Author(s):  
G. Zhang ◽  
Y. Wang ◽  
Y. Zhang ◽  
X. Wan ◽  
J. Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Breast Cancer Patients ◽  
Anti Cancer

COVID-19 outcomes in patients with a history of breast cancer: A diverse multicenter Los Angeles cohort study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12544-e12544
Author(s):  
Nikhita Kathuria-Prakash ◽  
Lauren Antrim ◽  
Alexander W Sun ◽  
Irene Kang ◽  
Maria De Lourdes Garcia-Jimenez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cohort Study ◽  
Los Angeles ◽  
Cancer Treatment ◽  
Cancer Patients ◽  
Hospitalization Rate ◽  
Breast Cancer Patients ◽  
Treatment History ◽  
History Of ◽  
Extent Of Disease

e12544 Background: Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 has affected over 100 million individuals during the current pandemic. Cancer is a reported risk factor for worse outcomes from SARS-CoV-2 infection and its clinical syndrome COVID-19. However, risk associated with specific cancer subtypes, extent of disease, and treatment history remains unclear. Breast cancer is the most common cancer in women and is treated with multiple modalities that may affect COVID-19 severity and outcomes, including surgery, radiation (RT), hormone therapy (HT), and chemotherapy (CT). Methods: We conducted a retrospective cohort study of patients with SARS-CoV-2 and history of breast cancer at two academic centers in Los Angeles, CA between January – September, 2020. Demographic information, cancer diagnosis, treatment history, comorbid conditions, and clinical outcomes of COVID-19 were reviewed. The primary outcome was rate of hospitalization for COVID-19. Associations were evaluated for significance by chi-square test or Student’s T test, with a = 0.05. Results: Our cohort included 61 patients with history of breast cancer. 19 (31.1%) required hospitalization and 3 (4.9%) died from COVID-19. Median age was 61 years. 44% of patients were White/Caucasian, 37.7% Hispanic/Latinx, 8% Black/African American, 5% Asian, and 5% were of another race. 87% of patients had local or regional disease and 13% had distant metastases. 53% of patients had ever received CT historically, 66% HT, and 53% RT. 25% of patients received cancer treatment (surgery, CT, or RT) within 90 days of COVID-19 diagnosis. 38% were on HT at time of COVID-19 diagnosis. Patients with prior RT were more likely to be hospitalized from COVID-19 than those with no prior RT (44% vs 14%, p = 0.02), as were patients with 2 or more comorbidities (p = 0.01). In addition, there was a trend toward lower hospitalization rates for patients on HT [24% vs. 42% (p = 0.17)] and a trend toward higher hospitalization rate for non-white ethnicity [35% vs. 25% (p = ns)]. Extent of disease, history of CT, or receipt of any cancer treatment (e.g. surgery, RT, CT) within 90 days of COVID-19 diagnosis were not associated with hospitalization rate. Conclusions: In our diverse cohort of breast cancer patients with COVID-19 a history of RT and presence of multiple comorbidities were both associated with increased risk of hospitalization, while a history of HT was not. Further investigation is needed to validate these findings in larger cohorts. These findings may inform recommendations for breast cancer patients during the ongoing SARS-CoV-2 pandemic.

Factors influencing options in primary breast cancer treatment.

1987 ◽  
Vol 5 (1) ◽  
pp. 68-74 ◽  
Author(s):  
W H Wolberg ◽  
M A Tanner ◽  
E P Romsaas ◽  
D L Trump ◽  
J F Malec
Keyword(s):  
Breast Cancer ◽  
Cancer Treatment ◽  
Cancer Patients ◽  
Primary Breast Cancer ◽  
Breast Cancer Treatment ◽  
Cancer Information ◽  
Breast Cancer Patients ◽  
Term Survival ◽  
Tumor Excision ◽  
Factors Influencing

Primary breast cancer treatment is determined by tumor factors and by patient preference. Breast cancer treatments that preserve the cosmetic appearance of the breast are appealing and effective for appropriately selected patients; long-term survival following tumor excision and breast irradiation appears to be comparable to that for mastectomy. Since April 1981, when a protocol was developed and treatment options were offered, factors influencing treatment selection have been analyzed in 206 consecutive primary breast cancer patients. Mastectomy was dictated by tumor-related factors in 96 patients (47%); 110 patients (53%) had the option of mastectomy or conservation--tumor excision plus radiotherapy to the breast. Among these 110 eligible patients, 54 chose conservation (49%) and 56 chose mastectomy (51%). Intraoperative findings for ten patients electing conservation necessitated mastectomy, so conservation was accomplished for 44 (21%) of those treated for breast cancer. Beginning in July 1982, breast cancer patients took a battery of psychosexual assessments before any operation (Profile of Mood States [POMS], Health Locus of Control Scale [HLCS] Locke-Wallace Marital Adjustment Test [MAT], Psychosocial Adjustment to Illness Scale [PAIS], Derogatis Sexual Function Inventory [DSFI], Millon Clinical Multiaxial Inventory [MCMI], and a Breast Cancer Information Test [BCIT]). Comparisons of psychologic and demographic variables were made between patients who chose mastectomy and those who chose conservation. No demographic variable was statistically significantly related to choice, although older women tended to select mastectomy more than younger women. Compared with those who elected conservation, women who elected mastectomy were more tense and anxious (P less than .01), more introverted (P less than .01), felt more depressed and dejected (P less than .05), and reported more sexual problems (P less than .05). Those who elected conservation valued their physical appearance more highly (P less than .01) and were generally more self-interested (P less than .05). Mastectomy was dictated by medical considerations for approximately half of patients with breast cancer. Among candidates for breast conservation, the importance of retaining the breast appeared to be determined to a significant degree by measurable psychological factors.

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