The latest medical research on Oncology
The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about oncology gathered by our medical AI research bot.
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Tumour predisposition and cancer syndromes as models to study gene-environment interactions.Nature Reviews Cancer
Cell division and organismal development are exquisitely orchestrated and regulated processes. The dysregulation of the molecular mechanisms underl...
Inhibition of SETMAR-H3K36me2-NHEJ repair axis in residual disease cells prevent glioblastoma recurrence.Neuro-Oncology
Residual disease of glioblastoma (GBM) causes recurrence. However, targeting residual cells have failed due to their inaccessibility and our lack of understanding their survival mechanisms to radiation therapy. Here we deciphered residual cell specific survival mechanism essential for GBM relapse.
Therapy Resistant Residual (RR) cells were captured from primary patient samples and cell line models mimicking clinical scenario of radiation resistance. Molecular signaling of resistance in RR cells was identified using RNA sequencing, genetic and pharmacological perturbations, overexpression systems, molecular and biochemical assays. Findings were validated in patient samples and orthotopic mouse model.
RR cells form more aggressive tumors than the parental cells in orthotopic mouse model. Upon radiation-induced damage, RR cells preferentially activated non homologous end joining (NHEJ) repair pathway, up-regulating Ku80 and Artemis while down-regulating of Mre11 at protein but not RNA levels. Mechanistically, RR cells upregulate SETMAR, mediating high levels of H3K36me2 and global euchromatization. High H3K36me2 leads to efficiently recruiting NHEJ proteins. Conditional knockdown of SETMAR in RR cells induced irreversible senescence partly mediated by reduced H3K36me2. RR cells expressing mutant H3K36A could not retain Ku80 at DSBs thus, compromising NHEJ repair leading to apoptosis and abrogation of tumorigenicity in vitro and in vivo. Pharmacological inhibition of NHEJ pathway phenocopied H3K36 mutation effect, confirming dependency of RR cells on NHEJ pathway for their survival.
We demonstrate that SETMAR- NHEJ regulatory axis is essential for the survival of clinically relevant radiation resistant residual cells, abrogation of which prevents recurrence in GBM.
Ad-CD40L mobilizes CD4 T cells for the treatment of brainstem tumors.Neuro-Oncology
Diffuse Midline Glioma, formerly Diffuse Intrinsic Pontine Glioma (DIPG), is the deadliest pediatric brainstem tumor with median survival of less than one year. Here, we investigated 1) whether direct delivery of adenovirus expressing CD40L (Ad-CD40L) to brainstem tumors would induce immune-mediated tumor clearance and, 2) if so, whether therapy would be associated with a manageable toxicity due to immune-mediated inflammation in the brainstem.
Syngeneic gliomas in the brainstems of immune competent mice were treated with Ad-CD40L and survival, toxicity and immune profiles determined. A clinically translatable vector, whose replication would be tightly restricted to tumor cells, rAd-Δ24-CD40L, was tested in human patient-derived Diffuse Midline Gliomas and immunocompetent models.
Expression of Ad-CD40L restricted to brainstem gliomas by pre-infection induced complete rejection, associated with immune cell infiltration, of which CD4+ T cells were critical for therapy. Direct intra-tumoral injection of Ad-CD40L into established brainstem tumors improved survival and induced some complete cures but with some acute toxicity. RNA-seq analysis showed that Ad-CD40L therapy induced neuroinflammatory immune responses associated with IL-6, IL-1β and TNF-α. Therefore, to generate a vector whose replication, and transgene expression, would be tightly restricted to tumor cells, we constructed rAd-Δ24-CD40L, the backbone of which has already entered clinical trials for Diffuse Midline Glioma. Direct intra-tumoral injection of rAd-Δ24-CD40L, with systemic blockade of IL-6 and IL-1β, generated significant numbers of cures with readily manageable toxicity.
Virus-mediated delivery of CD40L has the potential to be effective in treating Diffuse Midline Gliomas without obligatory neuroinflammation-associated toxicity.
Deregulated expression of the imprinted DLK1-DIO3 region in Glioblastoma Stem-like Cells: tumor suppressor role of lncRNA MEG3.Neuro-Oncology
Glioblastoma (GBM) stem-like cells (GSCs) are thought to be responsible for the maintenance and aggressiveness of GBM, the most common primary brain tumor in adults. This study aims at elucidating the involvement of deregulations within the imprinted DLK-DIO3 region on chromosome 14q32 in GBM pathogenesis.
RT-PCR analyses were performed on GSCs and GBM tissues. Methylation analyses, gene expression and Reverse-Phase protein Array profiles were used to investigate the tumor suppressor function of MEG3.
Loss of expression of genes and non-coding RNAs within the DLK1-DIO3 region was observed in GSCs and GBM tissues compared to normal brain. This down-regulation is mainly mediated by epigenetic silencing. Kaplan-Meier analysis indicated that low expression of MEG3 and MEG8 lncRNAs significantly correlated with short survival in GBM patients. MEG3 restoration impairs tumorigenic abilities of GSCs in vitro by inhibiting cell growth, migration and colony formation and decreases in vivo tumor growth reducing infiltrative growth. These effects were associated with modulation of genes involved in cell adhesion and Epithelial to Mesenchymal Transition (EMT).
In GBM, MEG3 acts as a tumor-suppressor mainly regulating cell adhesion, EMT and cell proliferation, thus providing a potential candidate for novel GBM therapies.
Rare cancers in India: A road less travelled.Indian Journal of Cancer
Globally, rare cancers as a group are commoner than any single common cancer. They represent an unmet medical need, and this issue gets further amp...
Unusual cause of seizure in a child: Intracranial calcified metastasis of osteosarcoma.Indian Journal of Cancer
Intracranial parenchymal calcification has both benign and malignant etiologies. Calcifications by malignant etiologies are comparatively rare. Mal...
A wrong diagnosis.Indian Journal of Cancer
Cancer therapy is undergoing rapid advancements and many of the conditions that were incurable earlier can now easily be treated. Making a "correct...
The Positive Impact of Infectious Diseases Consultation on Antimicrobial Appropriateness in Hospitalized Patients with Antimicrobial Stewardship Oversight: A propensity-score matched study.Antimicrobial Agents and Chemotherapy
Hospital-based antibiotic stewardship (AS) programs provide oversight and guidance for appropriate antimicrobial use in acute care settings. Infectious Diseases expertise is beneficial in the care of hospitalized patients with infections. The impact of Infectious Diseases consultation (IDC) on antimicrobial appropriateness in a large tertiary hospital with an established AS program was investigated.
This was a cross-sectional study from 10/2017 to 3/2019 at a large, academic hospital with an AS-directed prospective audit and feedback process and multiple IDC services. Antimicrobial appropriateness was adjudicated by an AS team member after antimicrobial start. Antimicrobial appropriateness was compared among antimicrobial orders with and without IDC using propensity-score matching and multivariable logistic regression. Analyses were stratified by primary services caring for the patients.
There were 10,508 antimicrobial orders from 6,165 unique patient encounters. Overall appropriateness was 92% with higher appropriateness among patients with IDC vs. without IDC, (94% vs 84%, p<0.0001). After propensity-score matching and adjustment for certain antibiotics, organisms, syndromes and locations, IDC was associated with greater antimicrobial appropriateness odds ratio (OR) 2.4 (95% confidence interval (CI) 1.9, 3.0). Stratification by primary service showed OR of 2.9 (95% CI 2.1, 3.8) for surgical specialties and OR of 1.6 (95% CI 1.1, 2.2) for medical specialties.
Even with a high overall antimicrobial appropriateness, patients with IDC had greater odds of antimicrobial appropriateness than those without IDC and this impact was greater in surgical specialties. Infectious disease consultation can be synergistic with antimicrobial stewardship programs.
Reduced susceptibility to carbapenems in a Klebsiella pneumoniae clinical isolate producing SCO-1 and CTX-M-15 beta-lactamases together with OmpK35 and OmpK36 porin deficiency.Antimicrobial Agents and Chemotherapy
Extended-spectrum beta-lactamases (ESBLs) and carbapenemases are among the most important causes of resistance in Enterobacterales, often leading t...
Human-Simulated Antimicrobial Regimens in Animal Models: Transparency and Validation are Imperative.Antimicrobial Agents and Chemotherapy
Animal infection models are invaluable to optimizing antimicrobial dosage in humans. Utilization of human-simulated regimens (HSR) in animal models...
Dysregulated haematopoietic stem cell behaviour in myeloid leukaemogenesis.Nature Reviews Cancer
Haematopoiesis is governed by haematopoietic stem cells (HSCs) that produce all lineages of blood and immune cells. The maintenance of blood homeos...
p53: 800 million years of evolution and 40 years of discovery.Nature Reviews Cancer
The evolutionarily conserved p53 protein and its cellular pathways mediate tumour suppression through an informed, regulated and integrated set of ...