Measurement of tumour protein synthesis in vivo in human colorectal and breast cancer and its variability in separate biopsies from the same tumour

1991 ◽  
Vol 80 (6) ◽  
pp. 587-593 ◽  
Author(s):  
S. D. Heys ◽  
K. G. M. Park ◽  
M. A. McNurlan ◽  
A. G. Calder ◽  
V. Buchan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protein Synthesis ◽  
Cancer Patients ◽  
Intravenous Injection ◽  
Sampling Error ◽  
Breast Cancer Patients ◽  
Colorectal Tumour ◽  
The Mean ◽  
Colorectal Tumours

1. A method is described for measuring the rates of protein synthesis in vivo in human colorectal and breast tumours by the intravenous injection of l-[1-13C]leucine as a ‘flooding dose'. 2. The incorporation of isotope into colorectal tumour protein was measured in six patients, whose tumours were biopsied after the injection. Fractional rates of protein synthesis were calculated from the enrichment of leucine in protein and the average free leucine enrichment in plasma. The range of rates obtained was 17.2–33.9%/day, with a mean rate (± sem) of 22.5 ± 2.6%/day. 3. Tumour protein synthesis rates were also measured in 15 patients with breast cancer. The range of rates obtained was 5.3–15.9%/day, with a mean rate (± sem) of 10.3 ± 0.8%/day. These rates are significantly lower than those obtained with colorectal tumours (P < 0.001). 4. In 9 of the breast cancer patients, protein synthesis was measured in multiple random biopsies taken from the same tumour. The mean (± sem) difference between the highest and lowest rates in biopsies from the same tumour was only 1.1 ± 0.3%/day. Only 13% of the variation in protein synthesis between separate tumours could be explained by sampling error because of variation within the tumour itself, the remainder being genuine variation between individual tumours.

scholarly journals Prospective superficial EPR in-vivo dosimetry study during hypofractionated radiotherapy of breast cancer patients treated with helical tomotherapy

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Sebastian Höfel ◽  
Matteo Gandalini ◽  
Michael K. Fix ◽  
Malte Drescher ◽  
Felix Zwicker
Keyword(s):  
Breast Cancer ◽  
Total Dose ◽  
Cancer Patients ◽  
Helical Tomotherapy ◽  
Planning System ◽  
In Vivo Dosimetry ◽  
Breast Cancer Patients ◽  
Displacement Vectors ◽  
The Mean

Abstract Background In-vivo dosimetry (IVD) is a patient specific measure of quality control and safety during radiotherapy. With regard to current reporting thresholds for significant occurrences in radiotherapy defined by German regulatory authorities, the present study examines the clinical feasibility of superficial electron paramagnetic resonance (EPR) IVD of cumulative total doses applied to breast cancer patients treated with helical intensity-modulated radiotherapy (tomotherapy). Methods In total, 10 female patients with left- or right-sided breast cancer were enrolled in this prospective IVD study. Each patient received a hypofractionated whole breast irradiation. A total median dose of 42.4 Gy in 16 fractions (5 fractions per week) was prescribed to the planning target volume. The treatments were completely delivered using helical tomotherapy and daily image guidance via megavoltage CT (MVCT). For each patient, three EPR dosimeters were prepared and placed at distinct locations on the patient’s skin during the delivery of all fractions. Two dosimeters were placed next to the ipsilateral and contralateral mammilla and one dosimeter was placed ventrally to the thyroid (out-of-primary-beam). The total doses delivered to the dosimeters were readout after all fractions had been administered. The measured total dose values were compared to the planned dose values derived from the treatment planning system (TPS). Daily positional variations (displacement vectors) of the ipsilateral mammilla and of the respective dosimeter were analyzed with respect to the planned positions using the daily registered MVCT image. Results Averaged over all patients, the mean absolute dose differences between measured and planned total dose values (± standard deviation (SD)) were: 0.49 ± 0.85 Gy for the ipsilateral dosimeter, 0.17 ± 0.49 Gy for the contralateral dosimeter and -0.12 ± 0.30 Gy for the thyroid dosimeter. The mean lengths of the ipsilateral displacement vectors (± SD) averaged over all patients and fractions were: 10 ± 7 mm for the dosimeter and 8 ± 4 mm for the mammilla. Conclusion Superficial EPR IVD is suitable as additional safeguard for dose delivery during helical tomotherapy of breast cancer. Despite positional uncertainties in clinical routine, the observed dose deviations at the ipsilateral breast were on average small compared to national reporting thresholds for total dose deviations (i.e. 10%/4 Gy). EPR IVD may allow for the detection of critical dose errors during whole breast irradiations.

Correlation of AGR2 expression with the incidence of metastasis in luminal breast cancer

2021 ◽  
pp. 1-5
Author(s):  
David Samuel Kereh ◽  
John Pieter ◽  
William Hamdani ◽  
Haryasena Haryasena ◽  
Daniel Sampepajung ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Mean Value ◽  
Rank Test ◽  
Luminal Breast Cancer ◽  
P Value ◽  
Strong Positive Correlation ◽  
Breast Cancer Patients ◽  
The Mean ◽  
Spearman Test

BACKGROUND: AGR2 expression is associated with luminal breast cancer. Overexpression of AGR2 is a predictor of poor prognosis. Several studies have found correlations between AGR2 in disseminated tumor cells (DTCs) in breast cancer patients. OBJECTIVE: This study aims to determine the correlation between anterior Gradient2 (AGR2) expression with the incidence of distant metastases in luminal breast cancer. METHODS: This study was an observational study using a cross-sectional method and was conducted at Wahidin Sudirohusodo Hospital and the network. ELISA methods examine AGR2 expression from blood serum of breast cancer patients. To compare the AGR2 expression in metastatic patients and the non-metastatic patient was tested with Mann Whitney test. The correlation of AGR2 expression and metastasis was tested with the Rank Spearman test. RESULTS: The mean value of AGR2 antibody expression on ELISA in this study was 2.90 ± 1.82 ng/dl, and its cut-off point was 2.1 ng/dl. Based on this cut-off point value, 14 subjects (66.7%) had overexpression of AGR2 serum ELISA, and 7 subjects (33.3%) had not. The mean value AGR2 was significantly higher in metastatic than not metastatic, 3.77 versus 1.76 (p < 0.01). The Spearman rank test obtained a p-value for the 2 tail test of 0.003 (p < 0.05), which showed a significant correlation of both, while the correlation coefficient of 0.612 showed a strong positive correlation of AGR2 overexpression and metastasis. CONCLUSIONS: AGR2 expression is correlated with metastasis in Luminal breast cancer.

Targeting PKM2 promotes chemosensitivity of breast cancer cells in vitro and in vivo

2021 ◽  
pp. 1-10
Author(s):  
Yu Wang ◽  
Han Zhao ◽  
Ping Zhao ◽  
Xingang Wang
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Poor Prognosis ◽  
Breast Cancer Cells ◽  
Breast Cancer Patients ◽  
Cancer Tissues

BACKGROUND: Pyruvate kinase M2 (PKM2) was overexpressed in many cancers, and high PKM2 expression was related with poor prognosis and chemoresistance. OBJECTIVE: We investigated the expression of PKM2 in breast cancer and analyzed the relation of PKM2 expression with chemotherapy resistance to the neoadjuvant chemotherapy (NAC). We also investigated whether PKM2 could reverse chemoresistance in breast cancer cells in vitro and in vivo. METHODS: Immunohistochemistry (IHC) was performed in 130 surgical resected breast cancer tissues. 78 core needle biopsies were collected from breast cancer patients before neoadjuvant chemotherapy. The relation of PKM2 expression and multi-drug resistance to NAC was compared. The effect of PKM2 silencing or overexpression on Doxorubicin (DOX) sensitivity in the MCF-7 cells in vitro and in vivo was compared. RESULTS: PKM2 was intensively expressed in breast cancer tissues compared to adjacent normal tissues. In addition, high expression of PKM2 was associated with poor prognosis in breast cancer patients. The NAC patients with high PKM2 expression had short survival. PKM2 was an independent prognostic predictor for surgical resected breast cancer and NAC patients. High PKM2 expression was correlated with neoadjuvant treatment resistance. High PKM2 expression significantly distinguished chemoresistant patients from chemosensitive patients. In vitro and in vivo knockdown of PKM2 expression decreases the resistance to DOX in breast cancer cells in vitro and tumors in vivo. CONCLUSION: PKM2 expression was associated with chemoresistance of breast cancers, and could be used to predict the chemosensitivity. Furthermore, targeting PKM2 could reverse chemoresistance, which provides an effective treatment methods for patients with breast cancer.

scholarly journals Lesion-Based Bone Metastasis Detection in Chest Bone Scintigraphy Images of Prostate Cancer Patients Using Pre-Train, Negative Mining, and Deep Learning

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 518
Author(s):  
Da-Chuan Cheng ◽  
Te-Chun Hsieh ◽  
Kuo-Yang Yen ◽  
Chia-Hung Kao
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Deep Learning ◽  
Bone Metastasis ◽  
Cancer Patients ◽  
Bone Scintigraphy ◽  
Breast Cancer Patients ◽  
Location Detection ◽  
The Mean ◽  
Mean Sensitivity

This study aimed to explore efficient ways to diagnose bone metastasis early using bone scintigraphy images through negative mining, pre-training, the convolutional neural network, and deep learning. We studied 205 prostate cancer patients and 371 breast cancer patients and used bone scintigraphy data from breast cancer patients to pre-train a YOLO v4 with a false-positive reduction strategy. With the pre-trained model, transferred learning was applied to prostate cancer patients to build a model to detect and identify metastasis locations using bone scintigraphy. Ten-fold cross validation was conducted. The mean sensitivity and precision rates for bone metastasis location detection and classification (lesion-based) in the chests of prostate patients were 0.72 ± 0.04 and 0.90 ± 0.04, respectively. The mean sensitivity and specificity rates for bone metastasis classification (patient-based) in the chests of prostate patients were 0.94 ± 0.09 and 0.92 ± 0.09, respectively. The developed system has the potential to provide pre-diagnostic reports to aid in physicians’ final decisions.

scholarly journals Integrin alpha5 in human breast cancer is a mediator of bone metastasis and a therapeutic target for the treatment of osteolytic lesions

Oncogene ◽  
2021 ◽  
Author(s):  
Francesco Pantano ◽  
Martine Croset ◽  
Keltouma Driouch ◽  
Natalia Bednarz-Knoll ◽  
Michele Iuliani ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Bone Metastasis ◽  
Tumor Cell ◽  
Cancer Patients ◽  
Breast Cancer Patients ◽  
Osteolytic Lesions ◽  
Cell Colonization

AbstractBone metastasis remains a major cause of mortality and morbidity in breast cancer. Therefore, there is an urgent need to better select high-risk patients in order to adapt patient’s treatment and prevent bone recurrence. Here, we found that integrin alpha5 (ITGA5) was highly expressed in bone metastases, compared to lung, liver, or brain metastases. High ITGA5 expression in primary tumors correlated with the presence of disseminated tumor cells in bone marrow aspirates from early stage breast cancer patients (n = 268; p = 0.039). ITGA5 was also predictive of poor bone metastasis-free survival in two separate clinical data sets (n = 855, HR = 1.36, p = 0.018 and n = 427, HR = 1.62, p = 0.024). This prognostic value remained significant in multivariate analysis (p = 0.028). Experimentally, ITGA5 silencing impaired tumor cell adhesion to fibronectin, migration, and survival. ITGA5 silencing also reduced tumor cell colonization of the bone marrow and formation of osteolytic lesions in vivo. Conversely, ITGA5 overexpression promoted bone metastasis. Pharmacological inhibition of ITGA5 with humanized monoclonal antibody M200 (volociximab) recapitulated inhibitory effects of ITGA5 silencing on tumor cell functions in vitro and tumor cell colonization of the bone marrow in vivo. M200 also markedly reduced tumor outgrowth in experimental models of bone metastasis or tumorigenesis, and blunted cancer-associated bone destruction. ITGA5 was not only expressed by tumor cells but also osteoclasts. In this respect, M200 decreased human osteoclast-mediated bone resorption in vitro. Overall, this study identifies ITGA5 as a mediator of breast-to-bone metastasis and raises the possibility that volociximab/M200 could be repurposed for the treatment of ITGA5-positive breast cancer patients with bone metastases.

Aesthetic outcome and patient’s quality of life in breast cancer patients undergoing mastectomy with or without immediate reconstruction.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12587-e12587
Author(s):  
Sidra Afzal ◽  
Asad Parvaiz ◽  
Nida Javed
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Well Being ◽  
Mean Difference ◽  
Breast Cancer Patients ◽  
Immediate Reconstruction ◽  
Patient’S Satisfaction ◽  
Group A ◽  
The Mean ◽  
Group B

e12587 Background: : Although post mastectomy Immediate breast reconstruction has shown to improve physical and psychosocial well-being of breast cancer patients, this is not a usual procedure in Pakistan due to limited resources and lack of awareness. The aim of our study is to evaluate patient’s satisfaction/ aesthetic outcomes between the patients undergoing mastectomy alone (Group A) and the ones undergoing mastectomy followed by immediate reconstruction (Group B). Methods: This is a prospective study conducted at Shaukat Khanum Hospital Pakistan comparing aesthetic outcome, patient’s satisfaction and Quality of life between two groups using Breast Q module. All patients undergoing mastectomy with and without reconstruction between April 2017 to July 2019 are included. Sample size of 84 was calculated (42 in each group). Results: The mean Q score of satisfaction with the breast in group B is 82.64 and in group A is 35.82 (P = 0.001). The mean Q score of Psychosocial well-being in group B is 89 vs 44.95 in group A (P = 0.001). The mean Q score of Physical well-being in group B is 98.23 vs 90.41 in group A (P = 0.002). The mean Q score of sexual well-being in group B is 81.93 vs 43 in Group A (P = 0.001). [Mean difference in score of 5-10 - little change, 10-20 - moderate change, > 20 - significant change].The mean difference between two groups in satisfaction with breast , psychosocial well-being and sexual well-being is more than 20 with a statistically significant p-value, while in physical well-being the mean difference is 7.8 which falls in little change group. Conclusions: Our study shows that reconstruction helps breast cancer patients in providing comprehensive care in a manner that they achieve a higher satisfaction with their appearance, psychological and sexual well-being without compromising oncological safety and this should be practiced more in our country. Also patients education about these procedures should be raised to help them fighting against this disease

scholarly journals Roles of Superoxide dismutase(SOD) , Malondialdehyde (MDA), 8-iso-prostaglandinF2α ( 8-iso-PGF2α)as oxidative stress in development and progression of Brest cancer in Iraqi females patients

2020 ◽  
Vol 25 (1) ◽  
pp. 1-4
Author(s):  
Ferdous Abbas Jabir ◽  
Ahmed Sabah Shaker
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Cancer Patients ◽  
Antioxidant Defenses ◽  
Blood Levels ◽  
P Value ◽  
Oxygen Species ◽  
Breast Cancer Patients ◽  
Markers Of Oxidative Stress ◽  
The Mean

               Oxidative stress occurs as a result of disturbance in the balance between the production of reactive oxygen species (free radicals) and antioxidant defenses. Markers of oxidative stress were measured the markers of oxidative stress in breast cancer patients after diagnosis of breast cancer and compared these plasma blood levels controls This study was conducted to three markers of oxidative stress ;these are (SOD) enzyme ,malondialdehyde (MDA)and8-iso-prostaglandinF2α plasma of patients with breast cancer and compare with controls .In this study ;  the mean MDA (ng/ml) levels for the breast cancer patients and the controls were55.91±3.31 and40.61±3.76  respectively, while the SOD (pg/ml) levels were1530.37±80.4 and1851.4 9±93.65  respectively and the 8-iso-PGF2α (ng/ml ) levels were 40.16±3.31 and 30.16±2.34  difference of the mean were statistically significant (p value <0.05).                                                                                                                       

Survival Outcomes In Human Epidermal Growth Factor Receptor 2 (HER 2) Positive Breast Cancer Patients At Kenyatta National Hospital

2021 ◽  
Author(s):  
Gloria Tuwei ◽  
Amsalu Degu
Keyword(s):  
Breast Cancer ◽  
Survival Rate ◽  
Cancer Patients ◽  
Survival Outcomes ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Predictors Of Mortality ◽  
Her2 Positive Breast Cancer ◽  
The Mean ◽  
Positive Breast Cancer

Abstract Background: For several years, HER2-positive breast cancer was associated with poor outcomes and higher mortality rates than other breast cancer subtypes. Nevertheless, the advent of Trastuzumab has significantly changed the treatment paradigm of HER2-positive breast cancer. However, it is not an affordable treatment option in sub-Saharan African countries. Besides, there was a lack of comprehensive data about the survival outcomes of HER2-positive breast cancer patients in our setting. Hence, the present study aimed to determine the survival outcomes among HER2-positive breast cancer patients at the Oncology Department of Kenyatta National Hospital.Methods: A hospital-based retrospective cohort design was used to evaluate the survival outcomes, and associated factors among patients with HER2-positive breast cancer admitted between 2015 and 2019 at Kenyatta National Hospital. A total of 50 eligible HER2-positive breast cancer patients were included in the study. In the pre-designed data abstraction tool, the data were collected by reviewing the medical records of the patients. The data were entered and analyzed using the Statistical Package for the Social Sciences version 27 software. The mean survival time was estimated using Kaplan Meier survival analysis. Cox regression analysis was employed to estimate the predictors of mortality among HER2-positive breast cancer patients.Results: The study showed that the overall survival rate was 30%, with a significant decrease in the percentage survival rate across the five years. More than half of the study participants (26, 52%) showed cancer progression during the last follow-up period. The present study showed that the mean cancer-specific survival rate among the study patients was 26.74±18.395 months. The study showed that the mean survival time of patients aged below 60 years (32.513 months), without co-morbidities (34.40 months), and the early stage of the disease (50.639 months) was higher than their counterparts. Multivariate cox-regression analysis revealed that advanced stage (AHR=13.1, 95% CI=2.6-66.6, P=0.002 and distant metastasis (AHR=15.0, 95% CI=3.6-62.8, P≤0.001) were the significant predictors of mortality among HER2 positive breast cancer patients.Conclusions: The overall survival rate of HER 2 positive breast cancer was 30%. Advanced stage and distant metastasis were the significant predictors of mortality among HER2-positive breast cancer patients.

Serum ANGPTL2 Levels Reflect Clinical Features of Breast Cancer Patients: Implications for the Pathogenesis of Breast Cancer Metastasis

2014 ◽  
Vol 29 (3) ◽  
pp. 239-245 ◽  
Author(s):  
Motoyoshi Endo ◽  
Yutaka Yamamoto ◽  
Masahiro Nakano ◽  
Tetsuro Masuda ◽  
Haruki Odagiri ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Clinical Features ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Cancer Metastasis ◽  
Ductal Carcinoma ◽  
Breast Cancer Metastasis ◽  
Breast Cancer Patients

Introduction Breast cancer is a leading cause of cancer-related death in women worldwide, and its metastasis is a major cause of disease mortality. Therefore, identification of the mechanisms underlying breast cancer metastasis is crucial for the development of therapeutic and diagnostic strategies. Our recent study of immunodeficient female mice transplanted with MDA-MB231 breast cancer cells demonstrated that tumor cell-derived angiopoietin-like protein 2 (ANGPTL2) accelerates metastasis through both increasing tumor cell migration in an autocrine/paracrine manner, and enhancing tumor angiogenesis. To determine whether ANGPTL2 contributes to its clinical pathogenesis, we asked whether serum ANGPTL2 levels reflect the clinical features of breast cancer progression. Methods We monitored the levels of secreted ANGPTL2 in supernatants of cultured proliferating MDA-MB231 cells. We also determined whether the circulating ANGPTL2 levels were positively correlated with cancer progression in an in vivo breast cancer xenograft model using MDA-MB231 cells. Finally, we investigated whether serum ANGPTL2 levels were associated with clinical features in breast cancer patients. Results Both in vitro and in vivo experiments showed that the levels of ANGPTL2 secreted from breast cancer cells increased with cell proliferation and cancer progression. Serum ANGPTL2 levels in patients with metastatic breast cancer were significantly higher than those in healthy subjects or in patients with ductal carcinoma in situ or non-metastatic invasive ductal carcinoma. Serum ANGPTL2 levels in patients negative for estrogen receptors and progesterone receptors, particularly triple-negative cases, reflected histological grades. Conclusions These findings suggest that serum ANGPTL2 levels in breast cancer patients could represent a potential marker of breast cancer metastasis.

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