Genomic and transcriptomic profiling of radioresistant prostate and head and neck cancers implicate a BAHD1-dependent modification of DNA damage at the heterochromatin.

Radiotherapy is an integral modality in treating human cancers, but radioresistance remains a clinical challenge due to the involvement of multiple intrinsic cellular and extrinsic tumour microenvironment factors that govern radiosensitivity. To study the intrinsic factors that are associated with cancer radioresistance, we established 4 radioresistant prostate (22Rv1 and DU145) and head and neck cancer (FaDu and HK1) models by irradiating their wild-type parentals to 90 Gy, mimicking the fractionated radiotherapy schema that is often using in the clinic, and performed whole exome and transcriptome sequencing of the radioresistant and wild-type models. Comparative genomic analyses detected the enrichment of mismatch repair mutational signatures (SBS6, 14, 15, 20) across all the cell lines and several non-synonymous single nucleotide variants involved in pro-survival pathways.

The immunomodulatory role of paracrine signalling factor VSIG4 in peritoneal metastases.

Peritoneal metastasis (PM), the regional progression of intra-abdominal malignancies, is a common sequelae of colorectal cancer (CRC). Immunotherapy is slated to be effective in generating long-lasting anti-tumour response as it utilizes the specificity and memory of the immune system. In the tumour microenvironment, tumour associated macrophages (TAMs) are posited to create an anti-inflammatory pro-tumorigenic environment.

Transcriptomic convergence despite genomic divergence drive field cancerization in synchronous squamous tumors.

Introduction: Field cancerization is suggested to arise from imbalanced differentiation in individual basal progenitor cells leading to clonal expansion of mutant cells that eventually replace the epithelium, although without evidence.

Methods: We performed deep sequencing analyses to characterize the genomic and transcriptomic landscapes of field change in two patients with synchronous aerodigestive tract tumors.

Results: Our data support the emergence of numerous genetic alterations in cancer-associated genes but refutes the hypothesis that founder mutation(s) underpin this phenomenon.

Radical resection and hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of high risk recurrent retroperitoneal sarcoma-A pilot study in a tertiary Asian centre.

Background: Peritoneal sarcomatosis (PS) is a difficult entity to treat with limited options and guarded prognosis. We aimed to determine if the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) could offer superior local recurrence-free survival in patients with retroperitoneal sarcoma at high risk of developing PS as opposed to extended resection alone.

Methods: This is a single arm, phase II intervention study where all patients with recurrent localized retroperitoneal sarcoma considered at high risk of developing PS were considered for enrolment (ClinicalTrials.

Vinorelbine Improves the Efficacy of Sorafenib against Hepatocellular Carcinoma: A Promising Therapeutic Approach.

Hepatocellular carcinoma (HCC) is a leading global cause of cancer-related mortality. Despite the widespread adoption of sorafenib as the standard HCC treatment, its efficacy is constrained, frequently encountering resistance. To augment the effectiveness of sorafenib, this study investigated the synergy of sorafenib and vinorelbine using 22 HCC patient-derived xenograft (PDX) models.

Everolimus Acts in Synergy with Vinorelbine to Suppress the Growth of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a challenging cancer to treat, as traditional chemotherapies have shown limited effectiveness. The mammalian target of rapamycin/sirolimus (mTOR) and microtubules are prominent druggable targets for HCC. In this study, we demonstrated that co-targeting mTOR using mTOR inhibitors (everolimus and sirolimus) along with the microtubule inhibitor vinorelbine yielded results superior to those of the monotherapies in HCC PDX models.

A Systematic Review and Meta-Analysis of Mapping Biopsy for Primary Extramammary Paget's Disease in Reducing Recurrence Following Surgical Excision.

Objective: To examine the association between the performance of mapping biopsies and surgical outcomes postexcision of extramammary Paget's disease (EMPD).

Background: Primary EMPD is a rare entity associated with poorly defined surgical margins and difficult-to-access sites of lesions. Surgical resection with clear margins remains the preferred management method.

High intra-abdominal pressure during hyperthermic intraperitoneal chemotherapy (HIPEC) following cytoreductive surgery (CRS) for peritoneal surface malignancies.

Objective: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) represent a mainstay of treatment for peritoneal malignancies. There is evidence that HIPEC using high intra-abdominal pressure (IAP) results in increased tissue penetration, although its safety profile remains relatively unknown. We thus aim to evaluate differences in intra- and post-operative outcomes in patients undergoing CRS-HIPEC with different levels of IAP.

A systematic review of margin status in retroperitoneal liposarcomas: Does the R0 margin matter?

Retroperitoneal liposarcomas (RPLPSs) are a rare tumor group for which current guidelines recommend aggressive resection to attain microscopically negative (R0) margins. To ensure R0 margins, resection of adherent or adjacent organs is often required. However, it is still unclear if R0 margins confer any additional benefit to patients over a grossly negative but microscopically positive (R1) margin.

Prospective Comparison of the Performance of MRI Versus CT in the Detection and Evaluation of Peritoneal Surface Malignancies.

Background: The performance of MRI versus CT in the detection and evaluation of peritoneal surface malignancies (PSM) remains unclear in the current literature. Our study is the first prospective study in an Asian center comparing the two imaging modalities, validated against intra-operative findings. Methods: A total of 36 patients with PSM eligible for CRS-HIPEC underwent both MRI and CT scans up to 6 weeks before the operation.

Ligand-mediated PAI-1 inhibition in a mouse model of peritoneal carcinomatosis.

Peritoneal carcinomatosis (PC) present a ubiquitous clinical conundrum in all intra-abdominal malignancies. Via functional and transcriptomic experiments of ascites-treated PC cells, we identify STAT3 as a key signaling pathway. Integrative analysis of publicly available databases and correlation with clinical cohorts (n = 7,359) reveal putative clinically significant activating ligands of STAT3 signaling.

Amplified parallel antigen rapid test for point-of-care salivary detection of SARS-CoV-2 with improved sensitivity.

In the ongoing COVID-19 pandemic, simple, rapid, point-of-care tests not requiring trained personnel for primary care testing are essential. Saliva-based antigen rapid tests (ARTs) can fulfil this need, but these tests require overnight-fasted samples; without which independent studies have demonstrated sensitivities of only 11.7 to 23.

A machine learning approach to identify predictive molecular markers for cisplatin chemosensitivity following surgical resection in ovarian cancer.

Ovarian cancer is associated with poor prognosis. Platinum resistance contributes significantly to the high rate of tumour recurrence. We aimed to identify a set of molecular markers for predicting platinum sensitivity.

Predicting Early and Late Readmissions Following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

Background: Postoperative readmissions not only burden the healthcare system but may also affect clinical outcomes of cancer patients. Despite this, little is known about readmissions after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), or their impact on survival outcomes.

Patients And Methods: A single-institution retrospective cohort study of CRS-HIPEC procedures from April 2001 and September 2019 was performed.

Gene Expression Changes Associated with Dedifferentiation in Liposarcoma Predict Overall Survival.

Up to 10% of well-differentiated liposarcoma (WDLS) progress to dedifferentiated liposarcoma (DDLS). We aimed to identify gene expression changes associated with dedifferentiation and whether these were informative of tumour biology of DDLS. We analysed datasets from the Gene Expression Omnibus (GEO, ID = GSE30929) database to identify differentially expressed genes between WDLS ( = 52) and DDLS ( = 39).

Effect of the learning curve of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) on the treatment of colorectal peritoneal metastasis.

Background: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) are increasingly utilised in the management of colorectal peritoneal metastases (CPM). This combined modality is associated with a significant learning curve (LC) and is often criticised for its associated morbidity. This study aims to inspect the LC of this procedure in our institute.

Virtual Multidisciplinary Review of a Complex Case Using a Digital Clinical Decision Support Tool to Improve Workflow Efficiency.

Objective: Integration of distinct clinical perspectives in multi-disciplinary tumor board meetings is critical to determine optimal patient care. Digital tools can support the data consolidation needed for meeting preparation and data sharing during complex case reviews. In this paper, we assessed the value of a clinical decision support tool on workflow efficiency and conducting a complex case review of a dermatofibrosarcoma protuberans (DFSP) tumor.

Postoperative Inflammatory Marker Surveillance in Colorectal Peritoneal Carcinomatosis.

Background: The prognostic significance of inflammatory markers in solid cancers is well-established, albeit with considerable heterogeneity. This study sought to investigate the postoperative inflammatory marker trend in peritoneal carcinomatosis (PC), with a focus on colorectal PC (CPC), and to propose optimal surveillance periods and cutoffs.

Methods: Data were collected from a prospectively maintained database of PC patients treated at the authors' institution from April 2001 to March 2019.

Factors associated with returning to work in head and neck cancer survivors in Singapore: A preliminary exploratory mixed-methods approach study.

Background: Little is known about return-to-work (RTW) among Asian head and neck cancer (HNC) survivors. We investigated the prevalence and factors associated with RTW among HNC patients with in Singapore.

Methods: In this cross-sectional mixed-methods study, 80 HNC patients, who had been working prior to diagnosis, completed questionnaires and 15 participated in qualitative interviews to explore perceived barriers and facilitators of RTW.

Clinical implications of systemic and local immune responses in human angiosarcoma.

Angiosarcomas are a rare subtype of soft-tissue sarcomas which exhibit aggressive clinical phenotypes with limited treatment options and poor outcomes. In this study, we investigated the clinical relevance of the peripheral blood neutrophil-to-lymphocyte ratio (NLR) as a marker of systemic immune response, as well as its correlation with intra-tumoral immune profiles in a subgroup of cases (n = 35) using the NanoString PanCancer IO360 panel and multiplex immunohistochemistry. In the overall cohort (n = 150), angiosarcomas of the head and neck (AS-HN) comprised most cases (58.

A functional network of gastric-cancer-associated splicing events controlled by dysregulated splicing factors.

Comprehensive understanding of aberrant splicing in gastric cancer is lacking. We RNA-sequenced 19 gastric tumor-normal pairs and identified 118 high-confidence tumor-associated (TA) alternative splicing events (ASEs) based on high-coverage sequencing and stringent filtering, and also identified 8 differentially expressed splicing factors (SFs). The TA ASEs occurred in genes primarily involved in cytoskeletal organization.

Pairing a prognostic target with potential therapeutic strategy for head and neck cancer.

Objectives: We have previously identified and validated a panel of molecular prognostic markers (ATP13A3, SSR3, and ANO1) for Head and Neck Squamous Cell Carcinoma (HNSCC). The aim of this study was to investigate the consequence of ATP13A3 dysregulation on signaling pathways, to aid in formulating a therapeutic strategy targeting ATP13A3-overexpressing HNSCC.

Materials And Methods: Gene Set Enrichment Analysis (GSEA) was performed on HNSCC microarray expression data (Internal local dataset [n = 92], TCGA [n = 232], EMBL [n = 81]) to identify pathways associated with high expression of ATP13A3.