A review on gold nanoparticles radiosensitization effect in radiation therapy of cancer

In the recent years, application of nanoparticles in diagnosis and treatment of cancer has been the issue of extensive research. Among these studies some have focused on the dose enhancement effect of gold nanoparticles (GNPs) in radiation therapy of cancer. On the other hand, some studies indicated energy dependency of dose enhancement effect, and the others have studied the GNP size effect in association with photon energy. However, in some aspects of GNP-based radiotherapy the results of recent studies do not seem very conclusive in spite of relative agreement on the basic physical interaction of photoelectric between GNPs and low energy photons. The main idea behind the GNP dose enhancement in some studies is not able to explain the results especially in recent investigation on cell lines and animal models radiation therapy using GNPs. In the present article the results of the available reports and articles were analyzed and compared and the final status of the GNP-RT was discussed.     

Towards breast cancer rotational radiotherapy with synchrotron radiation

PurposeWe performed the first investigations, via measurements and Monte Carlo simulations on phantoms, of the feasibility of a new technique for synchrotron radiation rotational radiotherapy for breast cancer (SR³T).MethodsA Monte Carlo (MC) code based on Geant4 toolkit was developed in order to simulate the irradiation with the SR³T technique and to evaluate the skin sparing effect in terms of centre-to-periphery dose ratio at different energies in the range 60–175 keV. Preliminary measurements were performed at the Australian Synchrotron facility. Radial dose profiles in a 14-cm diameter polyethylene phantom were measured with a 100-mm pencil ionization chamber for different beam sizes and compared with the results of MC simulations. Finally, the dose painting feasibility was demonstrated with measurements with EBT3 radiochromic films in a phantom and collimating the SR beam at 1.5 cm in the horizontal direction.ResultsMC simulations showed that the SR³T technique assures a tumour-to-skin absorbed dose ratio from about 7:1 (at 60 keV photon energy) to about 10:1 (at 175 keV), sufficient for skin sparing during radiotherapy. The comparison between the results of MC simulations and measurements showed an agreement within 5%. Two off-centre foci were irradiated shifting the rotation centre in the horizontal direction.ConclusionsThe SR³T technique permits to obtain different dose distributions in the target with multiple rotations and can be guided via synchrotron radiation breast computed tomography imaging, in propagation based phase-contrast conditions. Use of contrast agents like iodinated solutions or gold nanoparticles for dose enhancement (DE-SR³T) is foreseen and will be investigated in future work.     

A six-gene-based signature for breast cancer radiotherapy sensitivity estimation

Breast cancer (BRCA) represents the most common malignancy among women worldwide with high mortality. Radiotherapy is a prevalent therapeutic for BRCA that with heterogeneous effectiveness among patients. Here, we proposed to develop a gene expression-based signature for BRCA radiotherapy sensitivity estimation. Gene expression profiles of BRCA samples from the Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) were obtained and used as training and independent testing dataset, respectively. Differential expression genes (DEGs) in BRCA samples compared with their paracancerous samples in the training set were identified by using the edgeR Bioconductor package. Univariate Cox regression analysis and LASSO Cox regression method were applied to screen optimal genes for constructing a radiotherapy sensitivity estimation signature. Nomogram combining independent prognostic factors was used to predict 1-, 3-, and 5-year OS of radiation-treated BRCA patients. Relative proportions of tumor infiltrating immune cells (TIICs) calculated by CIBERSORT and mRNA levels of key immune checkpoint receptors was adopted to explore the relation between the signature and tumor immune response. As a result, 603 DEGs were obtained in BRCA tumor samples, six of which were retained and used to construct the radiotherapy sensitivity prediction model. The signature was proved to be robust in both training and testing sets. In addition, the signature was closely related to the immune microenvironment of BRCA in the context of TIICs and immune checkpoint receptors’ mRNA levels. In conclusion, the present study obtained a radiotherapy sensitivity estimation signature for BRCA, which should shed new light in clinical and experimental research.     

Metabolomic studies of breast cancer in murine models: A review

BackgroundMetabolomic strategies have been extensively used to search for biomarkers of disease, including cancer, in biological complex mixtures such as cells, tissues and biofluids. In breast cancer research, murine models are of great value and metabolomics has been increasingly applied to characterize tumor or organ tissues, or biofluids, for instance to follow-up metabolism during cancer progression or response to specific therapies.Scope of reviewThis review briefly introduces the different murine models used in breast cancer research and proceeds to present the metabolomic studies reported so far to describe the deviant metabolic behavior associated to breast cancer, in each type of model: xenografts (cell- or patient-derived), spontaneous (naturally-occurring or genetically engineered) and carcinogen-induced. The type of sample and strategies followed are identified, as well as the main findings from of study.Major conclusionsMetabolomics has gradually become relevant in characterizing murine models of breast cancer, using either Nuclear Magnetic Resonance (NMR) or Mass Spectromety (MS). Both tissue and biofluids are matrixes of interest in this context, although in some type of models, reports have focused primarily on the former. The aims of tissue studies have comprised the search for mechanistic knowledge of carcinogenesis, metastasis development and response/resistance to therapies. Biofluid metabolomics has mainly aimed at finding non-invasive biomarkers for early breast cancer detection or prognosis determination.General significanceMetabolomics provides exquisite detail on murine tumor and systemic metabolism of breast cancer. This knowledge paves the way for the discovery of new biomarkers, potentially translatable to in vivo non-invasive patient follow-up.     

Matrix metalloproteases and TIMPs as prognostic biomarkers in breast cancer patients treated with radiotherapy: A pilot study

Breast cancer (BC) is the most common tumour in women and one of the most important causes of cancer death worldwide. Radiation therapy (RT) is widely used for BC treatment. Some proteins have been identified as prognostic factors for BC (Ki67, p53, E‐cadherin, HER2). In the last years, it has been shown that variations in the expression of MMPs and TIMPs may contribute to the development of BC. The aim of this pilot work was to study the effects of RT on different MMPs (‐1, ‐2, ‐3, ‐7, ‐8, ‐9, ‐10, ‐12 and ‐13) and TIMPs (‐1 to ‐4), as well as their relationship with other variables related to patient characteristics and tumour biology. A group of 20 BC patients treated with RT were recruited. MMP and TIMP serum levels were analysed by immunoassay before, during and after RT. Our pilot study showed a slight increase in the levels of most MMP and TIMP with RT. However, RT produced a significantly decrease in TIMP‐1 and TIMP‐3 levels. Significant correlations were found between MMP‐3 and TIMP‐4 levels, and some of the variables studied related to patient characteristics and tumour biology. Moreover, MMP‐9 and TIMP‐3 levels could be predictive of RT toxicity. For this reason, MMP‐3, MMP‐9, TIMP‐3 and TIMP‐4 could be used as potential prognostic and predictive biomarkers for BC patients treated with RT.     

Nitroblue tetrazolium test in patients with breast cancer undergoing mastectomy and radiotherapy

The reduction of nitrotetrazolium blue with stimulated and unstimulated granulocytes was performed in 40 patients with breast cancer. Blood was collected from peripheral vein before surgical intervention, during surgery from vein draining of tumor, two weeks after surgery and three months after surgery when radiotherapy was finished. In parallel experiments the NBT test was made in the peripheral blood of 20 healthy individuals. We have observed decreased reduction of nitrotetrazolium blue in stimulated granulocytes, which may indicate that granulocytes from these patients are unable for efficient stimulation. No evident effect concerning the advancement of disease and applied therapy could be found. The importance of determining the NBT test in cancer patients is briefly discussed.     

Aminoglutethimide--a new endocrine therapy in breast cancer. A cancer research review

Aminoglutethimide is an effective treatment for advanced postmenopausal breast cancer, acting in a novel way. It inhibits peripheral and tumour aromatase, which converts androgens to oestrogens. Marked suppression of oestrone and oestradiol is produced. Aminoglutethimide was used as an inhibitor of adrenal steroid biosynthesis, but the concentrations required to inhibit aromatase in vitro are 10 times lower. This has led to its clinical evaluation in much lower doses. Doses of 125 mg twice daily produce oestrogen suppression equivalent to conventional doses of 1 g daily, and also similar tumour responses. Toxicity is much reduced by the lower dose.     

Hypofractionated radiotherapy in breast cancer: a 10-year single institution experience

BackgroundModerately post-operative hypofractionated radiotherapy (HYPO-RT) for breast cancer is a safe and effective strategy as seen in large prospective trials. This study aimed to assess overall and disease-free survivals, local control, and acute and late toxicities in patients treated with HYPO-RT.Materials and methodsData from patients submitted to post-operative HYPO-RT, with or without boost, were evaluated retrospectively. Demographic, disease, and treatment characteristics were collected.ResultsFrom March 2009 to December 2016, 393 patients were treated. Breast-conserving surgery was performed in 94.7%, immediate reconstruction after mastectomy in 6 (1.5%). Most patients (91.2%) had initial stage (0 to IIA), and chemotherapy was performed in 42.0%, HYPO-RT was mainly performed in 15 or 16 daily fractions of 267 cGy and 265 cGy, respectively. The median follow-up was 5.7 years. There were 25 deaths (6.4%) and 17 (4.3%) local recurrences. At 5 and 10 years, the overall survival, local control, and disease-free survival were, respectively, 96.0% and 79.3%, 99.2% and 94.9%, 96.6%, and 91.9%. Acute grade 3 or 4 dermatitis was observed in 0.9%. Late grade 1 or 2 occurred in less than 3% of the patients.ConclusionHYPO-RT is a safe and effective radiotherapy regimen with excellent disease control and overall survival rates, with low acute and late toxicity rates.     

Estrogen receptor agonists/antagonists in breast cancer therapy: A critical review

Estrogens display intriguing tissue selective action that is of great biomedical importance in the development of optimal therapeutics for the prevention and treatment of breast cancer. There are also strong evidences to show that both endogenous and exogenous estrogens are involved in the pathogenesis of breast cancer. Tamoxifen has been the only drug of choice for more than 30 years to treat patients with estrogen related (ER) positive breast tumors. There is a need therefore, for identifying newer, potential and novel candidates for breast cancer. Keeping this in view, the present review focuses on selective estrogen receptor modulators and estrogen antagonists such as sulfatase and aromatase inhibitors involved in breast cancer therapy. A succinct and critical overview of the structure of estrogen receptors, their signaling and involvement in breast carcinogenesis are herein described.     

Combinatorial effects of radiofrequency hyperthermia and radiotherapy in the presence of magneto-plasmonic nanoparticles on MCF-7 breast cancer cells

Here, the effects of combinatorial cancer therapy including radiotherapy (RT) and radiofrequency (RF) hyperthermia in the presence of gold-coated iron oxide nanoparticles (Au@IONPs), as a thermo-radio-sensitizer, are reported. The level of cell death and the ratio of Bax/Bcl2 genes, involved in the pathway of apoptosis, were measured to evaluate the synergistic effect of Au@IONPs-mediated RF hyperthermia and RT. MCF-7 human breast adenocarcinoma cells were treated with different concentrations of Au@IONPs. After incubation with NPs, the cells were exposed to RF waves (13.56 MHz; 100 W; 15 min). At the same time, thermometry was performed with an infrared (IR) camera. Then, the cells were exposed to 6 MV X-ray at various doses of 2 and 4 Gy. MTT (3-[4,5-dimethylthiazol-2-y1]-2,5-diphenyltetrazolium bromide) assay was performed to evaluate cell viability and quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the expression ratio of Bax/Bcl2. Cellular uptake of nanoparticles was confirmed qualitatively and quantitatively. The results obtained from MTT assay and qRT-PCR studies showed that NPs and RF hyperthermia had no significant effect when applied separately, while their combination had synergistic effects on cell viability percentage and the level of apoptosis induction. A synergistic effect was also observed when the cancer cells were treated with a combination of NPs, RF hyperthermia, and RT. On the basis of the obtained results, it may be concluded that the use of magneto-plasmonic NPs in the process of hyperthermia and RT of cancer holds a great promise to develop a new combinatorial cancer therapy strategy.     

Human Papillomavirus and the use of nanoparticles for immunotherapy in HPV-related cancer: A review

Human Papillomavirus (HPV) remains one of the most commonly contracted sexually transmitted diseases around the world. There are a multitude of HPV types, some of which may never present any symptoms. Others, however, are considered high-risk types, which increase the chance of the person infected to develop cancer. In recent years, the utilization of nanotechnology has allowed researchers to employ and explore the use of nanoparticles in immunotherapies.The new nanoparticle frontier has opened many doors in this area of research as a form of prevention, diagnosis, and treatment in cancers resulting from HPV. This review will provide a brief background of HPV, its relationship to head and neck cancer (HNC) and present some insight into the field of immunotherapeutic nanoparticles.     

Hypofractionated radiotherapy in young versus older women with breast cancer: a retrospective study from India

BackgroundYoung women with breast cancer (BC) are not represented in the trials on hypofractionation. In this study we compared outcomes in young patients with BC to their older counterparts treated with hypofractionated radiotherapy (RT) in a regional cancer centre in India.Materials and methodsBetween January 1990 to December 2010, women with BC, treated with hypofractionated RT dose of 35–40 Gy/15#/3 weeks were divided into two groups, ≤ 35 years and > 35 years. Outcomes compared were locoregional recurrence rate (LRR), locoregional recurrence-free survival (LRRFS), disease-free survival (DFS), overall survival (OS) and toxicities. LRRFS, DFS and OS were estimated using the Kaplan-Meier method.ResultsOf total 2244 patients, 359 were ≤ 35 years of age and 1885 were > 35 years. Patient and disease characteristics were comparable between the two groups, except that comorbidities were significantly higher in the > 35 years age group, more patients aged ≤ 35 years had nodal N3 disease, received chemotherapy and RT to internal mammary nodes and more patients in the > 35 years group received hormonal therapy. Median follow up was 10 years (range 1–30 years). LRR and distant metastases were comparable between the two groups. However, synchronous LRR and distant metastases were significantly higher in the ≤ 35 years group 18 (5.1%) as compared to the > 35 years group 39 (2.1%) with p = 0.018. Estimated 10-year LRRFS, DFS and OS were 92% vs. 94% (p = 0.95), 68% vs. 73%(p = 0.058) and 78% vs. 76% (p = 0.10) in ≤ 35 years and > 35 years, respectively. OS for stage 1 was comparable between the two groups. However, for stage 2 and 3 it was 77% vs. 82% (p = 0.048) and 53% vs. 62% (p = 0.045) in the ≤ 35 years and > 35 years group, respectively. Acute and late toxicity were similar in the two groups.ConclusionYoung BC patients had higher LRR and distant metastases. LRRFS, DFS and toxicities were comparable between the two groups. However, OS was poorer in young BC patients with stage 2 and 3 disease.     

Computer-aided diagnosis of breast cancer using cytological images: A systematic review

Cytological evaluation by microscopic image-based characterization [imprint cytology (IC) and fine needle aspiration cytology (FNAC)] plays an integral role in primary screening/detection of breast cancer. The sensitivity of IC and FNAC as a screening tool is dependent on the image quality and the pathologist’s level of expertise. Computer-aided diagnosis (CAD) is used to assists the pathologists by developing various machine learning and image processing algorithms. This study reviews the various manual and computer-aided techniques used so far in breast cytology. Diagnostic applications were studied to estimate the role of CAD in breast cancer diagnosis. This paper presents an overview of image processing and pattern recognition techniques that have been used to address several issues in breast cytology-based CAD including slide preparation, staining, microscopic imaging, pre-processing, segmentation, feature extraction and diagnostic classification. This review provides better insights to readers regarding the state of the art the knowledge on CAD-based breast cancer diagnosis to date.     

Definitive single fraction stereotactic ablative radiotherapy for inoperable early-stage breast cancer: A case report

We review a case of inoperable early stage breast cancer treated definitively with the use of stereotactic ablative radiotherapy (SABR). A 57-year-old female with a history of decompensated cirrhosis with early stage breast cancer was treated with 25 Gy in one fraction. At her 7-month follow up visit, there was a complete resolution of disease on imaging. This case represents a novel approach for the treatment of breast cancer with SABR when surgery is contraindicated.     

The breast cancer paradox: A systematic review of the association between area-level deprivation and breast cancer screening uptake in Europe

Breast cancer rates are lower amongst women from more socio-economically deprived areas. However, their mortality rates are higher. One explanation of this breast cancer paradox is that women from more deprived areas are less likely to attend breast cancer screening programmes. This systematic review is the first to examine this issue in Europe. A systematic review of Embase, Medline and PsychINFO (from 2008 to 2019) was undertaken (PROSPERO registration number: CRD42018083703). Observational studies were included if they were based in Europe, measured breast cancer screening uptake, compared at least two areas, included an area-level measure of socio-economic deprivation and were published in the English language. The Joanna Briggs Institute critical appraisal checklist was used to assess study quality and risk of bias. Thirteen studies from seven different European countries met our inclusion criteria and were included in the review. In ten of the thirteen studies, there was a significant negative association between screening uptake and area-level socio-economic deprivation – with women living in more socio-economically deprived neighbourhoods less likely to attend breast cancer screening. Although universal screening programmes were provided in most studies, there were still strong negative associations between screening uptake and area-level socio-economic deprivation. Future breast cancer screening strategies should acknowledge these challenges, and consider developing targeted interventions in more deprived areas to increase screening participation.