The development of pevonedistat in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML): hope or hype?

Myelodysplastic syndrome (MDS) is a clonal hematopoietic stem cell disorder clinically defined by cytopenias, bone marrow failure, and an increased risk of progressing to acute myeloid leukemia (AML). Traditionally, first-line treatment for patients with higher-risk MDS has been hypomethylating agents (HMAs). However, these agents have modest clinical activity as single agents.

Circulating Tumor Cell Transcriptomics as Biopsy Surrogates in Metastatic Breast Cancer.

Background: Metastatic breast cancer (MBC) and the circulating tumor cells (CTCs) leading to macrometastases are inherently different than primary breast cancer. We evaluated whether whole transcriptome RNA-Seq of CTCs isolated via an epitope-independent approach may serve as a surrogate for biopsies of macrometastases.

Methods: We performed RNA-Seq on fresh metastatic tumor biopsies, CTCs, and peripheral blood (PB) from 19 newly diagnosed MBC patients.

Single-route CNS prophylaxis for aggressive non-Hodgkin lymphomas: real-world outcomes from 21 US academic institutions.

Prophylaxis is commonly used to prevent central nervous sy stem (CNS) relapse in diffuse large B-cell lymphoma (DLBCL), with no clear standard of care. We retrospectively evaluated 1162 adult patients across 21 US academic centers with DLBCL or similar histologies who received single-route CNS prophylaxis as part of frontline therapy between 2013 and 2019. Prophylaxis was administered intrathecally(IT) in 894 (77%) and using systemic high-dose methotrexate (HD-MTX) in 236 (20%); 32 patients (3%) switched route due to toxicity and were assessed separately.

Incidence of radiation induced sarcoma attributable to radiotherapy in adults: A retrospective cohort study in the SEER cancer registries across 17 primary tumor sites.

Background: Previous studies have noted the incidence of radiation-induced sarcomas (RIS) but have not investigated the relative risk (RR) of developing RIS based on primary tumor organ disease site. By examining data from the Surveillance, Epidemiology, and End Results (SEER) database, we hypothesized that breast cancer would have a higher incidence of RIS compared to seventeen other primary cancer sites.

Methods: This was a retrospective cohort study that examined patients from SEER registries between 1973 and 2013.

The current status of the clinical utility of liquid biopsies in cancer.

: Liquid biopsies have attracted considerable attention as potential diagnostic, prognostic, predictive, and screening assays in oncology. The term liquid biopsies include circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) in the blood. While many liquid biopsy technologies are under active investigation, relatively few liquid biopsy assays have been proven to serve as a diagnostic surrogate for biopsies of metastatic disease as predictive biomarkers to guide the selection of therapy in the clinic.

Two synchronous malignancies: nodular melanoma and renal cell carcinoma in a patient with an underlying germline mutation.

Modernised genetic testing among patients with cancer has led to an increasing wealth of knowledge regarding cancer biology and aetiology. Furthermore, some germline mutations have the potential to direct therapeutic approaches as well. While mutations are well-established risk factors for breast and ovarian cancers, their impact on other cancers is less understood.

The potential for liquid biopsies in the precision medical treatment of breast cancer.

Currently the clinical management of breast cancer relies on relatively few prognostic/predictive clinical markers (estrogen receptor, progesterone receptor, HER2), based on primary tumor biology. Circulating biomarkers, such as circulating tumor DNA (ctDNA) or circulating tumor cells (CTCs) may enhance our treatment options by focusing on the very cells that are the direct precursors of distant metastatic disease, and probably inherently different than the primary tumor's biology. To shift the current clinical paradigm, assessing tumor biology in real time by molecularly profiling CTCs or ctDNA may serve to discover therapeutic targets, detect minimal residual disease and predict response to treatment.

Aldose reductase expression as a risk factor for cataract.

Aldose reductase (AR) is thought to play a role in the pathogenesis of diabetic eye diseases, including cataract and retinopathy. However, not all diabetics develop ocular complications. Paradoxically, some diabetics with poor metabolic control appear to be protected against retinopathy, while others with a history of excellent metabolic control develop severe complications.

Aldose reductase inhibition alleviates hyperglycemic effects on human retinal pigment epithelial cells.

Chronic hyperglycemia is an important risk factor involved in the onset and progression of diabetic retinopathy (DR). Among other effectors, aldose reductase (AR) has been linked to the pathogenesis of this degenerative disease. The purpose of this study was to investigate whether the novel AR inhibitor, beta-glucogallin (BGG), can offer protection against various hyperglycemia-induced abnormalities in human adult retinal pigment epithelial (ARPE-19) cells.

Design of an amide N-glycoside derivative of β-glucogallin: a stable, potent, and specific inhibitor of aldose reductase.

β-Glucogallin (BGG), a major component of the Emblica officinalis medicinal plant, is a potent and selective inhibitor of aldose reductase (AKR1B1). New linkages (ether/triazole/amide) were introduced via high yielding, efficient syntheses to replace the labile ester, and an original two-step (90%) preparation of BGG was developed. Inhibition of AKR1B1was assessed in vitro and using transgenic lens organ cultures, which identified the amide linked glucoside (BGA) as a stable, potent, and selective therapeutic lead toward the treatment of diabetic eye disease.