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Rationale and Objectives: To analyze CT and high-resolution MRI findings of nodal metastasis calcifications and determine the value of high-resolution MRI in detecting nodal calcifications in rectal cancer patients.Materials and Methods: In total, 229 rectal cancer patients were included. The CT was reviewed for the presence of nodal calcifications by two radiologists. High-resolution two-dimensional turbo spin-echo T2-weighted imaging (2D-TSE-T2WI) and fat-suppressed gadolinium-enhanced isotropic high-resolution three-dimensional gradient-echo T1-weighted imaging (3D-GRE-T1WI) were independently reviewed for nodal calcifications by the two radiologists at one-month and two-month intervals, respectively. The sensitivities, specificities and accuracies of the two high-resolution MRI in detecting nodal calcifications were calculated using CT results as a reference.Results: Regional calcified metastatic lymph nodes were found in 28 patients. The node-to-node evaluation revealed that 55 (98.2%) of the 56 calcified lymph nodes were metastatic. Fifty-one (92.7%) calcified metastatic lymph nodes displayed scattered fine punctate calcifications to different degrees on CT. In both types of high-resolution MRI, the calcifications demonstrated a patchy area of markedly reduced signal intensity in corresponding areas that were larger than those on CT. The sensitivity and accuracy of fat-suppressed gadolinium-enhanced isotropic high-resolution 3D-GRE-T1WI were significantly higher than those of high-resolution 2D-TSE-T2WI (76.8% vs 58.9%, P = 0.013; 98.3% vs 97.9%, P = 0.007; respectively).Conclusion: Metastatic nodal calcifications are characteristic imaging findings in rectal cancer. Calcifications are indicated by markedly reduced signal on high-resolution MRI, which will alert radiologists to scrutinize CT for nodal calcifications and aid in the accurate diagnosis of metastatic lymph nodes. [ABSTRACT FROM AUTHOR]

Conventional chemotherapy for multiple myeloma (MM) faces the challenges of a low complete remission rate and transformation to recurrence/refractory. The current MM first-line clinical drug Bortezomib (BTZ) faces the problem of enhanced tolerance and nonnegligible side effects. B cell maturation antigen (BCMA), for its important engagement in tumor signaling pathways and novel therapy technologies such as Chimeric antigen receptor T-Cell immunotherapy (CAR-T) and Antibody Drug Conjugate (ADC), has been identified as an ideal target and attracted attention in anti-MM therapy. Emerging nanotechnology provided feasible methods for drug delivery and new therapeutic strategies such as photothermal therapy (PTT). Herein, we developed a BCMA-Targeting biomimetic photothermal nanomissile BTZ@BPQDs@EM @anti-BCMA (BBE@anti-BCMA) by integration of BTZ, black phosphorus quantum dots (BPQDs), Erythrocyte membrane (EM) and BCMA antibody (anti-BCMA). We hypothesized that this engineered nanomissile could attack tumor cells in triple ways and achieve effective treatment of MM. Consequently, the intrinsic biomimetic nature of EM and the active targeting property of anti-BCMA enhanced the accumulation of therapeutic agents in the tumor site. Besides, owing to the decrease in BCMA abundance, the potential apoptosis-inducing ability was revealed. With the support of BPQDs' photothermal effect, Cleaved-Caspase-3 and Bax signal increased significantly, and the expression of Bcl-2 was inhibited. Furthermore, the synergistic photothermal/chemo therapy can effectively inhibit tumor growth and reverse the disorder of NF-κB in vivo. Importantly, this biomimetic nanodrug delivery system and antibody induced synergistic therapeutic strategy efficiently killed MM cells with ignorable systemic toxicity, which is a promising method for the future anticancer treatment of hematological malignancies in clinics. [ABSTRACT FROM AUTHOR]

Multiple myeloma is a plasma cell malignancy, accounting for approximately 1% of new cancer cases. It is the second most common hematological malignancy. Novel clinical agents such as the proteasome inhibitor-bortezomib, have shown improved survival rates in recent decades. However, multiple myeloma remains incurable, as most patients eventually relapse and become refractory to current treatments. Therefore, there is an urgent need for developing new regimens to overcome the bortezomib resistance. Here, we screened a library of 2370 bioactives and found that polyphyllin VII selectively suppressed multiple myeloma cell growth in vitro and in vivo. We identified moesin, one of the critical regulators of the Wnt/β-catenin pathway, as a target of polyphyllin VII by drug affinity responsive target stability assay and cellular thermal shift assay. Polyphyllin VII binds to moesin and induces its degradation via the ubiquitin-proteasome pathway, thereby impairing the Wnt/β-catenin pathway activity and leading to a reduction in the side population cells to overcome bortezomib resistance. Our study identified polyphyllin VII as a promising compound and moesin as a potential diagnostic and therapeutic target for treating multiple myeloma. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is incurable and the second most common hematologic malignancy in plasma cells. Multiple myeloma stem cell-like cells (MMSCs), a rare population of MM cells, are believed to be the major cause of drug resistance and high recurrence rates in patients with MM. Therefore, developing novel strategies to eradicate MMSCs may favor myeloma treatment. In this study, based on the drug repositioning strategy, we found that albendazole (ABZ), a broad-spectrum antiparasitic drug, selectively suppresses the proliferation of multiple myeloma cells in vitro and in vivo and decreases number of aldehyde dehydrogenase (ALDH)-positive MMSCs in MM. Furthermore, RNA-seq of MM cells after ABZ treatment revealed that inhibition of the nuclear factor kappa-B (NF-κB) pathway is a key mediator of ABZ against MM. Moreover, we demonstrated that ABZ can resensitize cells resistant to bortezomib and overcome MMSCs-induced bortezomib resistance by decreasing ALDH1+ MMSCs numbers. Our findings provide preclinical evidence for utilizing the previously known pharmacologically active drug albendazole for the treatment of multiple myeloma. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Outline of the anticancer properties and associated molecular mechanism mediated by lycorine. • Comprehensive analysis of the structure activity relationship associated with anticancer activity of lycorine. • Summary of the pharmacological aspects and implications for future directions with this compound. Abstract Nature is the most abundant source for novel drug discovery. Lycorine is a natural alkaloid with immense therapeutic potential. Lycorine is active in a very low concentration and with high specificity against a number of cancers both in vivo and in vitro and against various drug-resistant cancer cells. This review summarized the therapeutic effect and the anticancer mechanisms of lycorine. At the same time, we have discussed the pharmacology and comparative structure-activity relationship for the anticancer activity of this compound. The researches outlined in this paper serve as a foundation to explain lycorine as an important lead compound for new generation anticancer drug design and provide the principle for the development of biological strategies to utilize lycorine in the treatment of cancers. [ABSTRACT FROM AUTHOR]