The impact of a regionally based translational cancer research collaborative in Australia using the FAIT methodology.

Background: Translating research, achieving impact, and assessing impact are important aspirations for all research collaboratives but can prove challenging. The Hunter Cancer Research Alliance (HCRA) was funded from 2014 to 2021 to enhance capacity and productivity in cancer research in a regional centre in Australia. This study aimed to assess the impact and benefit of the HCRA to help inform future research investments of this type.

Detailed DNA methylation characterisation of phyllodes tumours identifies a signature of malignancy and distinguishes phyllodes from metaplastic breast carcinoma.

Phyllodes tumours (PTs) are rare fibroepithelial lesions of the breast that are classified as benign, borderline, or malignant. As little is known about the molecular underpinnings of PTs, current diagnosis relies on histological examination. However, accurate classification is often difficult, particularly for distinguishing borderline from malignant PTs.

It is not all about the alpha: elevated expression of p53β variants is associated with lower probability of survival in a retrospective melanoma cohort.

Background: Melanoma is the deadliest type of skin cancer and despite improvements in treatment outcomes, melanoma claimed 57,043 lives in 2020. In most malignancies, p53 mutation rates are above 50% and provide prognostic indications. However, in melanoma where less than a quarter of cases harbour a p53 mutation, the significance of the tumour suppressor may be questioned.

p53 isoform expression promotes a stemness phenotype and inhibits doxorubicin sensitivity in breast cancer.

In breast cancer, dysregulated TP53 expression signatures are a better predictor of chemotherapy response and survival outcomes than TP53 mutations. Our previous studies have shown that high levels of Δ40p53 are associated with worse disease-free survival and disruption of p53-induced DNA damage response in breast cancers. Here, we further investigated the in vitro and in vivo implications of Δ40p53 expression in breast cancer.

p53 Dysregulation in Breast Cancer: Insights on Mutations in the Network and p53 Isoform Expression.

In breast cancer, p53 expression levels are better predictors of outcome and chemotherapy response than mutation. Several molecular mechanisms that modulate p53 levels and functions, including p53 isoform expression, have been described, and may contribute to deregulated p53 activities and worse cancer outcomes. In this study, and regulators of the p53 pathway were sequenced by targeted next-generation sequencing in a cohort of 137 invasive ductal carcinomas and associations between the identified sequence variants, and p53 and p53 isoform expression were explored.

Association of psychological distress with arm morbidity symptoms in breast cancer survivors: outcomes from the use of PHQ-9 and GAD-7 questionnaires.

Background: Although higher survival rates of breast cancer are achieved these days, breast cancer survivors are challenged with unwanted side effects from treatment or management that affect physical, functional, and psychological well-being of an individual. This study aimed to assess psychological distress status in Malaysian breast cancer survivors and factors that affected the condition.

Methods: A cross-sectional study design was conducted on 162 breast cancer survivors from various breast cancer support groups in Malaysia.

The role of truncated p53 isoforms in the DNA damage response.

The tumour suppressor p53 is activated following genotoxic stress and regulates the expression of target genes involved in the DNA damage response (DDR). The discovery that p53 isoforms alter the transcription of p53 target genes or p53 protein interactions unveiled an alternative DDR. This review will focus on the role p53 isoforms play in response to DNA damage.

Alterations in the p53 isoform ratio govern breast cancer cell fate in response to DNA damage.

Our previous studies have shown that p53 isoform expression is altered in breast cancer and related to prognosis. In particular, a high ∆40p53:p53α ratio is associated with worse disease-free survival. In this manuscript, the influence of altered Δ40p53 and p53α levels on the response to standard of care DNA-damaging agents used in breast cancer treatment was investigated in vitro.

Evaluation of Circulating MicroRNAs and Adipokines in Breast Cancer Survivors with Arm Lymphedema.

Breast cancer-related lymphedema (BCRL) is a form of secondary lymphedema that is characterized by abnormal swelling of one or both arms due to the accumulation of lymph fluid in the interstitial tissue spaces, resulting from obstruction of the lymphatic vessels due to surgery insults, radiotherapy, or chemotherapy. Due to the multifactorial nature of this condition, the pathogenesis of secondary lymphedema remains unclear and the search for molecular factors associated with the condition is ongoing. This study aimed to identify serum microRNAs and adipokines associated with BCRL.

Cytoplasmic p53β Isoforms Are Associated with Worse Disease-Free Survival in Breast Cancer.

mutations are associated with tumour progression, resistance to therapy and poor prognosis. However, in breast cancer, 's overall mutation frequency is lower than expected (~25%), suggesting that other mechanisms may be responsible for the disruption of this critical tumour suppressor. p53 isoforms are known to enhance or disrupt p53 pathway activity in cell- and context-specific manners.

Verification and Validation of a Four-Gene Panel as a Prognostic Indicator in Triple Negative Breast Cancer.

Triple negative breast cancer (TNBC) is a highly aggressive subtype with a high rate of metastasis, early distant recurrence and resistance to therapy leading to worse survival than other breast cancer subtypes. There are no well-established biomarkers that can determine women who will do better and those who are likely to have poorer outcomes with TNBC, nor are there targeted therapies. Thus, the identification of prognostic and/or predictive biomarkers will enable tailored therapies based on their likelihood of disease outcomes and may prevent over- and under-diagnosis.

Crosstalk Between microRNAs and the Pathological Features of Secondary Lymphedema.

Secondary lymphedema is characterized by lymphatic fluid retention and subsequent tissue swelling in one or both limbs that can lead to decreased quality of life. It often arises after loss, obstruction, or blockage of lymphatic vessels due to multifactorial modalities, such as lymphatic insults after surgery, immune system dysfunction, deposition of fat that compresses the lymphatic capillaries, fibrosis, and inflammation. Although secondary lymphedema is often associated with breast cancer, the condition can occur in patients with any type of cancer that requires lymphadenectomy such as gynecological, genitourinary, or head and neck cancers.

Effect of p53 and its N-terminally truncated isoform, Δ40p53, on breast cancer migration and invasion.

Breast cancer is the most diagnosed malignancy in women, with over half a million women dying from this disease each year. In our previous studies, ∆40p53, an N-terminally truncated p53 isoform, was found to be upregulated in breast cancers, and a high ∆40p53 : p53α ratio was linked with worse disease-free survival. Although p53α inhibits cancer migration and invasion, little is known about the role of ∆40p53 in regulating these metastasis-related processes and its role in contributing to worse prognosis.

Assessment of Potential Risk Factors and Skin Ultrasound Presentation Associated with Breast Cancer-Related Lymphedema in Long-Term Breast Cancer Survivors.

Breast cancer has been reported to have the highest survival rate among various cancers. However, breast cancer survivors face several challenges following breast cancer treatment including breast cancer-related lymphedema (BCRL), sexual dysfunction, and psychological distress. This study aimed to investigate the potential risk factors of BCRL in long term breast cancer survivors.

Copy number variation in triple negative breast cancer samples associated with lymph node metastasis.

Triple negative breast cancer (TNBC) is a highly metastatic and aggressive subtype of breast cancer and cases presenting with lymph node involvement have worse outcomes. This study aimed to determine the regions of copy number variation (CNV) associated with lymph node metastasis in TNBC patients. CNV analyses were performed in a study cohort of 23 invasive ductal carcinomas (IDCs), 12 lymph node metastases (LNmets), and 7 normal adjacent tissues (NATs); as well as in an independent cohort containing 70 TNBC IDCs and the same 7 NATs.

Cross-Cultural Adaptation of the Functional Assessment of Cancer Therapy-Breast (FACT-B) in Malaysian Breast Cancer Survivors.

Introduction: The survival rate of female breast cancer survivors has been reported to be higher than other types of cancer in Malaysia. Nonetheless, breast cancer survivors face new challenges from unwanted side effects of treatment or management such as fatigue, psychological disturbance, or arm swelling, which can lead to the decline of quality of life (QOL). This study aims to adapt the Malay version of the Functional Assessment of Cancer Therapy-Breast (FACT-B) to evaluate the QOL and to test its reliability and validity in Malaysian breast cancer survivors.

Switching off Cancer: Is There a Role for Epigenetics?

Epigenetics is the study of heritable changes in gene expression that do not involve any change in DNA sequence and include methylation, histone modifications, and altered miRNA or lncRNA expression [...

Intronic Polymorphisms Are Associated with Increased Transcript, Immune Infiltration and Cancer Risk.

We investigated the influence of selected SNPs in exon 4 and intron 4 on cancer risk, clinicopathological features and expression of isoforms. The intron 4 SNPs were significantly over-represented in cohorts of mixed cancers compared to three ethnically matched controls, suggesting they confer increased cancer risk. Further analysis showed that heterozygosity at rs1042522(GC) and either of the two intronic SNPs rs9895829(TC) and rs2909430(AG) confer a 2.

Good Cop, Bad Cop: Defining the Roles of Δ40p53 in Cancer and Aging.

The tumour suppressor p53 is essential for maintaining DNA integrity, and plays a major role in cellular senescence and aging. Understanding the mechanisms that contribute to p53 dysfunction can uncover novel possibilities for improving cancer therapies and diagnosis, as well as cognitive decline associated with aging. In recent years, the complexity of p53 signalling has become increasingly apparent owing to the discovery of the p53 isoforms.

Tetraspanin CD9 is Regulated by miR-518f-5p and Functions in Breast Cell Migration and In Vivo Tumor Growth.

Breast cancer is the most commonly diagnosed and the second leading cause of cancer-related mortality among women worldwide. miR-518f-5p has been shown to modulate the expression of the metastasis suppressor CD9 in prostate cancer. However, the role of miR-518f-5p and CD9 in breast cancer is unknown.

A Simple Migration/Invasion Workflow Using an Automated Live-cell Imager.

Cancer cell mobility is crucial for the initiation of metastasis. Therefore, investigation of the cell movement and invasive capacity is of great significance. Migration assays provide basic insight of cell movement at a 2D level, whereas invasion assays are more physiologically relevant, mimicking in vivo cancer cell dislodgment from the original site and invading through the extracellular matrix.

Molecular patterns of cancer colonisation in lymph nodes of breast cancer patients.

Lymph node (LN) metastasis is an important prognostic parameter in breast carcinoma, a crucial site for tumour-immune cell interaction and a gateway for further dissemination of tumour cells to other metastatic sites. To gain insight into the underlying molecular changes from the pre-metastatic, via initial colonisation to the fully involved LN, we reviewed transcriptional research along the evolving microenvironment of LNs in human breast cancers patients. Gene expression studies were compiled and subjected to pathway-based analyses, with an emphasis on immune cell-related genes.

The intron 3 16 bp duplication polymorphism of p53 (rs17878362) is not associated with increased risk of developing triple-negative breast cancer.

Purpose: Very little is known about the genetic risk factors associated with triple-negative breast cancer (TNBC), an aggressive clinical subtype characterised by the absence of ER, PR and HER2. p53, the tumour suppressor gene, is essential for maintaining genomic stability in response to cellular stress. In breast cancer, the mutation rates of TP53 vary depending on the subtype, such that ER-negative tumours have a high rate, and in ER-positive tumours they are less common.

Regulation of the human placental (pro)renin receptor-prorenin-angiotensin system by microRNAs.

Study Question: Are any microRNAs (miRNAs) that target the placental renin-angiotensin system (RAS) in the human placenta suppressed in early gestation?

Summary Answer: Overall, 21 miRNAs with predicted RAS mRNA targets were less abundant in early versus term placentae and nine were more highly expressed.

What Is Known Already: Regulation of human placental RAS expression could alter placental development and therefore normal pregnancy outcome. The expression of genes encoding prorenin (REN), angiotensinogen, (pro)renin receptor, angiotensin converting enzyme 2, and the angiotensin II type 1 receptor are highest in early gestation, at a time when oxygen tension is at its lowest.

Regulation of the interferon-gamma (IFN-γ) pathway by p63 and Δ133p53 isoform in different breast cancer subtypes.

The family consists of three sets of transcription factor genes, , and , each of which expresses multiple RNA variants and protein isoforms. Of these, is mutated in 25-30% of breast cancers. How mutations affect the interaction of family members and their isoforms in breast cancer is unknown.