Identification of Inappropriately Reprogrammed Genes by Large-Scale Transcriptome Analysis of Individual Cloned Mouse Blastocysts

Although cloned embryos generated by somatic/embryonic stem cell nuclear transfer (SECNT) certainly give rise to viable individuals, they can often undergo embryonic arrest at any stage of embryogenesis, leading to diverse morphological abnormalities. In an effort to gain further insights into reprogramming and the properties of SECNT embryos, we performed a large-scale gene expression profiling of 87 single blastocysts using GeneChip microarrays. Sertoli cells, cumulus cells, and embryonic stem cells were used as donor cells. The gene expression profiles of 87 blastocysts were subjected to microarray analysis. Using principal component analysis and hierarchical clustering, the gene expression profiles were clearly classified into 3 clusters corresponding to the type of donor cell. The results revealed that each type of SECNT embryo had a unique gene expression profile that was strictly dependent upon the type of donor cells, although there was considerable variation among the individual profiles within each group. This suggests that the reprogramming process is distinct for embryos cloned from different types of donor cells. Furthermore, on the basis of the results of comparison analysis, we identified 35 genes that were inappropriately reprogrammed in most of the SECNT embryos; our findings demonstrated that some of these genes, such as Asz1, Xlr3a and App, were appropriately reprogrammed only in the embryos with a transcriptional profile that was the closest to that of the controls. Our findings provide a framework to further understand the reprogramming in SECNT embryos

The Correlation of Magee Equations (TM) and Oncotype DX (R) Recurrence Score From Core Needle Biopsy Tissues in Predicting Response to Neoadjuvant Chemotherapy in ER+ and HER2- Breast Cancer

WOS: 000524026100008Objective: Oncotype DX (R) recurrence score (RS) can be predicted from Magee Equations (TM) (MS) postoperatively. The aim of this study is to investigate correlation of MS with RS from pretreatment core needle biopsy (CNB) [issues, and their clinical usefulness in prediction of response to neoadjuvant chemotherapy (NCT) in estrogen receptor-positive and human epidermal growth factor receptor 2-negative (ER+/HER2-) breast cancer (BC). Materials and Methods: Prerrearmenr CNB tissue samples from 60 patients with ER+ /HER2- invasive BC were analyzed for MS and RS correlation. MS and RS were categorized as follows low (= 31). Percentage Tumor size Reduction (%TR) was used to assess tumor response to NCT, and substantial %TR was defined as at least 50% reduction (.50%TR). Correlation between MS and RS, and predictisv factors for the >= 50%TR achievement were assessed. Results: MS and RS represen red a strong correlation (Spearman's correlation; r-0.58, p= 50% TR achievemenr, none of the factors were Magically significant (p >= 0.07). Conclusion: Our study demonstrated that there was a strong correlation between MS and RS from pretreatment biopsy tissue samples in ER+ and HER2- invasive. BC

Increased risk of SSEs in bone-only metastatic breast cancer patients treated with zoledronic acid

Background: Bone represents one of the most common sites to which breast cancer cells metastasize. Patients experience skeletal related adverse events (pathological fractures, spinal cord compressions, and irradiation for deteriorated pain on bone) even during treatment with zoledronic acid (ZA). Therefore, we conducted a retrospective cohort study to investigate the predictive factors for symptomatic skeletal events (SSEs) in bone-metastasized breast cancer (b-MBC) patients. Methods: We retrospectively collected data on b-MBC patients treated with ZA. Patient characteristics, including age, subtype, the presence of non-bone lesions, the presence of multiple bone metastases at the commencement of ZA therapy, duration of ZA therapy, the time interval between breast cancer diagnosis and the initiation of ZA therapy, and type of systemic therapy, presence of previous SSE were analyzed using multivariable logistic regression analysis. Results: The medical records of 183 patients were reviewed and 176 eligible patients were analyzed. The median age was 59 (range, 30–87) years. Eighty-seven patients were aged ≥60 years and 89 patients were aged < 60 years. The proportions of patients with estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2-positive disease were 81.8%, 63.1%, and 17.6%, respectively. Fifty-three patients had bone-only MBC at the commencement of ZA therapy. SSEs were observed in 42 patients. In the multivariable logistic regression analysis, bone-only MBC but not a breast cancer subtype was an independent risk factor for an SSE during ZA therapy (odds ratio: 3.878, 95% confidence interval: 1.647–9.481; p = 0.002). Conclusions: Bone-only MBC patients are more likely to experience an SSE even after treatment with ZA

Multinational Association of Supportive Care in Cancer (MASCC) clinical practice guidance for the prevention of breast cancer-related arm lymphoedema (BCRAL): international Delphi consensus-based recommendationsResearch in context

Summary: Background: Developing strategies to prevent breast cancer-related arm lymphoedema (BCRAL) is a critical unmet need because there are no effective interventions to eradicate it once it reaches a chronic state. Certain strategies such as prospective surveillance programs and prophylactic lymphatic reconstruction have been reported to be effective in clinical trials. However, a large variation exists in practice based on clinician preference, organizational standards, and local resources. Methods: A two-round international Delphi consensus process was performed from February 27, 2023 to May 25, 2023 to compile opinions of 55 experts involved in the care and research of breast cancer and lymphoedema on such interventions. Findings: Axillary lymph node dissection, use of post-operative radiotherapy, relative within-arm volume increase one month after surgery, greater number of lymph nodes dissected, and high body mass index were recommended as the most important risk factors to guide selection of patients for interventions to prevent BCRAL. The panel recommended that prospective surveillance programs should be implemented to screen for and reduce risks of BCRAL where feasible and resources allow. Prophylactic compression sleeves, axillary reverse mapping and prophylactic lymphatic reconstruction should be offered for patients who are at risk for developing BCRAL as options where expertise is available and resources allow. Recommendations on axillary management in clinical T1–2, node negative breast cancer patients with 1–2 positive sentinel lymph nodes were also provided by the expert panel. Routine axillary lymph node dissection should not be offered in these patients who receive breast conservation therapy. Axillary radiation instead of axillary lymph node dissection should be considered in the same group of patients undergoing mastectomy. Interpretation: An individualised approach based on patients' preferences, risk factors for BCRAL, availability of treatment options and expertise of the healthcare team is paramount to ensure patients at risk receive preventive interventions for BCRAL, regardless of where they are receiving care. Funding: This study was not supported by any funding. RJC received investigator grant support from the Australian National Health and Medical Research Council (APP1194051)