Analysis of immune responses in patients with CLL after heterologous COVID-19 vaccination.

Patients with chronic lymphocytic leukemia (CLL) treated with B-cell pathway inhibitors and anti-CD20 antibodies exhibit low humoral response rates following SARS-CoV-2 vaccination. To investigate this observation, a prospective single-institution study was conducted comparing peripheral blood mononuclear cell transcriptional response with antibody and T-cell response rates following heterologous BNT162b2/ChAdOx1 vaccination of 15 patients with CLL/small lymphocytic lymphoma (SLL). Two-dose antibody response rate was 40%, increasing to 53% after booster.

Comprehensive analysis of immune responses in CLL patients after heterologous COVID-19 vaccination.

Patients with chronic lymphocytic leukemia (CLL) treated with B-cell pathway inhibitors and anti-CD20 antibodies exhibit low humoral response rate (RR) following SARS-CoV-2 vaccination. To investigate the relationship between the initial transcriptional response to vaccination with ensuing B and T cell immune responses, we performed a comprehensive immune transcriptome analysis flanked by antibody and T cell assays in peripheral blood prospectively collected from 15 CLL/SLL patients vaccinated with heterologous BNT162b2/ChAdOx1 with follow up at a single institution. The two-dose antibody RR was 40% increasing to 53% after booster.

Predicting neoadjuvant chemoradiotherapy response with functional imaging and liquid biomarkers in locally advanced rectal cancer.

Introduction: Noninvasive predictive quantitative biomarkers are required to guide treatment individualization in patients with locally advanced rectal cancer (LARC) in order to maximize therapeutic outcomes and minimize treatment toxicity. Magnetic resonance imaging (MRI), positron emission tomography (PET), and blood biomarkers have the potential to predict chemoradiotherapy (CRT) response in LARC.

Areas Covered: This review examines the value of functional imaging (MRI and PET) and liquid biomarkers (circulating tumor cells (CTCs) and circulating tumor nucleic acid (ctNA)) in the prediction of CRT response in LARC.

Magnetic resonance imaging (MRI) guided proton therapy: A review of the clinical challenges, potential benefits and pathway to implementation.

Proton therapy and MRI-Linacs are two of the most exciting and fast growing technologies in radiation oncology. With over 100 MRI-Linacs and 100 proton therapy centres either in operation or under construction, an integrated approach that brings together the excellent soft tissue imaging of MRI with the superior dose conformity of proton therapy is compelling. The promise of MRI-guided proton therapy has prompted multiple research studies and the building of two pre-clinical experimental systems, taking us closer to realisation of this technology.

Genetic Predisposition to Persistent Human Papillomavirus-Infection and Virus-Induced Cancers.

Human papillomaviruses (HPVs) are the most common sexually transmitted pathogens worldwide and among the more than 200 identified HPV types, approximately 15 high risk (HR-HPV) types are oncogenic, being strongly associated with the development of cervical cancer, anogenital cancers and an increasing fraction of head and neck squamous cell carcinomas (HNSCC). HPV-associated cervix cancer accounts for 83% of HPV-attributable cancers, and more than two-thirds of those cases occur in developing countries. Despite the high frequency of HPV infections, in most cases, the virus is cleared by the host immune response and only a small proportion of infected individuals develop persistent infections that can result in malignant transformation, indicating that other elements, including biological, genetic and environmental factors may influence the individual susceptibility to HPV-associated cancers.

Multi-parametric magnetic resonance imaging assessment of whole tumour heterogeneity for chemoradiotherapy response prediction in rectal cancer.

Background And Purpose: Prediction of chemoradiotherapy response (CRT) in locally advanced rectal cancer would enable stratification of management. The purpose was to prospectively evaluate multi-parametric magnetic resonance imaging (MRI) assessment of tumour heterogeneity combining diffusion weighted imaging (DWI) and dynamic contrast enhanced (DCE) MRI for the prediction of CRT response in locally advanced rectal cancer.

Materials And Methods: Patients with Stage II or III rectal adenocarcinoma undergoing neoadjuvant CRT and surgery underwent MRI (DWI and DCE) before, during (week 3), and after CRT (1 week before surgery).

Phenomic screen identifies a role for the yeast lysine acetyltransferase NuA4 in the control of Bcy1 subcellular localization, glycogen biosynthesis, and mitochondrial morphology.

Cellular metabolism is tightly regulated by many signaling pathways and processes, including lysine acetylation of proteins. While lysine acetylation of metabolic enzymes can directly influence enzyme activity, there is growing evidence that lysine acetylation can also impact protein localization. As the Saccharomyces cerevisiae lysine acetyltransferase complex NuA4 has been implicated in a variety of metabolic processes, we have explored whether NuA4 controls the localization and/or protein levels of metabolic proteins.

Prognostic utility of serial F-FDG-PET/CT in patients with locally advanced rectal cancer who underwent tri-modality treatment.

Objective: This study explored the value of serial 18-fludeoxyglucose-positron emission tomography (F-FDG-PET/CT) in predicting disease-free survival (DFS) in locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiation (NCRT) and surgery.

Methods: We prospectively studied 46 patients with LARC who underwent NCRT and surgery. F-FDG-PET/CT scans were performed at three time-points before surgery (pre-NCRT-PET1, during NCRT-PET2 and following completion of NCRT-PET3).

Correlation of ultra-high field MRI with histopathology for evaluation of rectal cancer heterogeneity.

Current clinical MRI techniques in rectal cancer have limited ability to examine cancer stroma. The differentiation of tumour from desmoplasia or fibrous tissue remains a challenge. Standard MRI cannot differentiate stage T1 from T2 (invasion of muscularis propria) tumours.

Proteomic analysis defines kinase taxonomies specific for subtypes of breast cancer.

Multiplexed small molecule inhibitors covalently bound to Sepharose beads (MIBs) were used to capture functional kinases in luminal, HER2-enriched and triple negative (basal-like and claudin-low) breast cancer cell lines and tumors. Kinase MIB-binding profiles at baseline without perturbation proteomically distinguished the four breast cancer subtypes. Understudied kinases, whose disease associations and pharmacology are generally unexplored, were highly represented in MIB-binding taxonomies and are integrated into signaling subnetworks with kinases that have been previously well characterized in breast cancer.

Study protocol: multi-parametric magnetic resonance imaging for therapeutic response prediction in rectal cancer.

Background: Response to neoadjuvant chemoradiotherapy (CRT) of rectal cancer is variable. Accurate imaging for prediction and early assessment of response would enable appropriate stratification of management to reduce treatment morbidity and improve therapeutic outcomes. Use of either diffusion weighted imaging (DWI) or dynamic contrast enhanced (DCE) imaging alone currently lacks sufficient sensitivity and specificity for clinical use to guide individualized treatment in rectal cancer.

Characteristic expression of fukutin in gastric cancer among atomic bomb survivors.

Approximately 70 years have passed since the atomic bombs were dropped on Nagasaki and Hiroshima. To elucidate potential biomarkers and possible mechanisms of radiation-induced cancer, the expression of , which encodes fukutin protein and causes Fukuyama-type congenital muscular dystrophy, was analyzed in gastric cancer (GC) tissue samples from atomic bomb survivors. Expression of cluster of differentiation (CD) 10 was also evaluated, as it has previously been observed that positive fukutin expression was frequently noted in CD10-positive GC cases.

Lysine acetyltransferase NuA4 and acetyl-CoA regulate glucose-deprived stress granule formation in Saccharomyces cerevisiae.

Eukaryotic cells form stress granules under a variety of stresses, however the signaling pathways regulating their formation remain largely unknown. We have determined that the Saccharomyces cerevisiae lysine acetyltransferase complex NuA4 is required for stress granule formation upon glucose deprivation but not heat stress. Further, the Tip60 complex, the human homolog of the NuA4 complex, is required for stress granule formation in cancer cell lines.

Functional MRI for quantitative treatment response prediction in locally advanced rectal cancer.

Despite advances in multimodality treatment strategies for locally advanced rectal cancer and improvements in locoregional control, there is still a considerable variation in response to neoadjuvant chemoradiotherapy (CRT). Accurate prediction of response to neoadjuvant CRT would enable early stratification of management according to good responders and poor responders, in order to adapt treatment to improve therapeutic outcomes in rectal cancer. Clinical studies in diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) MRI have shown promising results for the prediction of therapeutic response in rectal cancer.

A functional polymorphism in the NKG2D gene modulates NK-cell cytotoxicity and is associated with susceptibility to Human Papilloma Virus-related cancers.

Human papillomavirus (HPV) is the most common sexually transmitted agent worldwide and is etiologically linked to several cancers, including cervical and genital cancers. NKG2D, an activating receptor expressed by NK cells, plays an important role in cancer immune-surveillance. We analyzed the impact of a NKG2D gene variant, rs1049174, on the incidence of HPV-related cancers in Vietnamese patients and utilized various molecular approaches to elucidate the mechanisms of NKG2D receptor regulation by rs1049174.

Induction of KIFC1 expression in gastric cancer spheroids.

Gastric cancer (GC) is one of the most common human cancers. Spheroid colony formation is an effective model for characterization of cancer stem cells. However, gene expression profiles of spheroid colonies obtained from GC cells have not been examined.

Left-sided breast cancer loco-regional radiotherapy with deep inspiration breath-hold: Does volumetric-modulated arc radiotherapy reduce heart dose further compared with tangential intensity-modulated radiotherapy?

Introduction: Left-sided breast cancer radiotherapy has been associated with an increase in cardiac mortality. This study investigated the potential heart-sparing effect of volumetric-modulated arc radiotherapy (VMAT). We compared VMAT to tangential intensity-modulated radiotherapy (t-IMRT) in the loco-regional treatment of left-sided breast cancer, including internal mammary nodal irradiation, based on deep inspiration breath-hold (DIBH) and free-breathing (FB).

Characteristic miR-24 Expression in Gastric Cancers among Atomic Bomb Survivors.

Objective: To elucidate the mechanism of radiation-induced cancers, we analyzed the expression profiles of microRNAs extracted from formalin-fixed paraffin-embedded (FFPE) gastric cancer (GC) tissue samples from atomic bomb survivors.

Methods: The expression levels of miR-21, miR-24, miR-34a, miR-106a, miR-143, and miR-145 were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR).

Results: The expression of microRNAs was measured by qRT-PCR in a Hiroshima University Hospital cohort comprising 32 patients in the high-dose-exposed group and 18 patients in the low-dose-exposed group who developed GC after the bombing.

MAP3K1: Genomic Alterations in Cancer and Function in Promoting Cell Survival or Apoptosis.

MAP3K1 is a member of the mitogen-activated protein kinase kinase kinase (MAP3K) family of serine/threonine kinases. MAP3K1 regulates JNK activation and is unique among human kinases in that it also encodes an E3 ligase domain that ubiquitylates c-Jun and ERK1/2. Full length MAP3K1 regulates cell migration and contributes to pro-survival signaling while its caspase 3-mediated cleavage generates a C-terminal kinase domain that promotes apoptosis.

The carbonic anhydrase isoforms of Chlamydomonas reinhardtii: intracellular location, expression, and physiological roles.

Aquatic photosynthetic organisms, such as the green alga Chlamydomonas reinhardtii, respond to low CO(2) conditions by inducing a CO(2) concentrating mechanism (CCM). Carbonic anhydrases (CAs) are important components of the CCM. CAs are zinc-containing metalloenzymes that catalyze the reversible interconversion of CO(2) and HCO(3)(-).

Desmoplastic neurotropic melanoma: a clinicopathologic analysis of 128 cases.

Background: Several studies have suggested that desmoplastic neurotropic melanoma (DNM) is associated with higher local recurrence rates than other types of melanoma. The authors investigated the local recurrence rates for patients with DNM after surgery alone or surgery followed by radiotherapy (RT).

Methods: One hundred twenty-eight patients with DNM were treated at the Sydney Melanoma Unit and the Sydney Cancer Center from 1996 to 2007.