Chemosensitivity enhanced by autophagy inhibition based on a polycationic nano-drug carrier

With increasing understanding of the role of autophagy in tumorigenesis and development, studies have demonstrated that both excessive induction and inhibition of autophagy could improve the efficacy against tumors during cytotoxic or molecularly targeted drug therapy.

Mesoporous Silica Nanoparticles

Integration of nanotechnology and biomedicine has offered great opportunities for the development of nanoscaled therapeutic platforms. Amongst various nanocarriers, mesoporous silica nanoparticles (MSNs) is one of the most developed and promising inorganic materials-based drug delivery system for clinical translations due to their simple composition and nanoporous structure. MSNs possess unique structural features, for example, well-defined morphology, large surface areas, uniform size, controllable structure, flexible pore volume, tunable pore sizes, extraordinarily high loading efficiency, and excellent biocompatibility. Progress in structure control and functionalization may endow MSNs with functionalities that enable medical applications of these integrated nanoparticles such as molecularly targeted drug delivery, multicomponent synergistic therapy, in vivo imaging and therapeutic capability, on-demand/stimuli-responsive drug release, etc. In this chapter, the authors overview MSNs' characteristics and the scientific efforts developed till date involving drug delivery and biomedical applications.

Brain Metastases From Hepatocellular Carcinoma: A Rare Case Report

Intrahepatic lesions of hepatocellular carcinoma (HCC) have been controlled by significant advances in treatment, including chemotherapy, surgery, and ablative therapy. Consequently, the number of patients with extrahepatic metastatic lesions has increased, including lung, regional lymph nodes, peritoneum, and adrenal glands, but rarely to the brain. The prognosis of brain metastasis remains poor, with approximately <1 y of survival from the time of diagnosis. Although no guidelines for the brain metastasis of HCC have been developed to date due to the lack of the experiences and pieces of evidence, a molecularly targeted drug, sorafenib, have been used to treat extrahepatic lesions and shown the prolonged survival time. Therefore, the development of standard therapy for brain metastasis following the early diagnosis is essential by accumulating the information of clinical courses and pieces of evidence.

Mesoporous Silica Nanoparticles

Integration of nanotechnology and biomedicine has offered great opportunities for the development of nanoscaled therapeutic platforms. Amongst various nanocarriers, mesoporous silica nanoparticles (MSNs) is one of the most developed and promising inorganic materials-based drug delivery system for clinical translations due to their simple composition and nanoporous structure. MSNs possess unique structural features, for example, well-defined morphology, large surface areas, uniform size, controllable structure, flexible pore volume, tunable pore sizes, extraordinarily high loading efficiency, and excellent biocompatibility. Progress in structure control and functionalization may endow MSNs with functionalities that enable medical applications of these integrated nanoparticles such as molecularly targeted drug delivery, multicomponent synergistic therapy, in vivo imaging and therapeutic capability, on-demand/stimuli-responsive drug release, etc. In this chapter, the authors overview MSNs' characteristics and the scientific efforts developed till date involving drug delivery and biomedical applications.

Molecularly targeted drug combinations demonstrate selective effectiveness for myeloid- and lymphoid-derived hematologic malignancies

Translating the genetic and epigenetic heterogeneity underlying human cancers into therapeutic strategies is an ongoing challenge. Large-scale sequencing efforts have uncovered a spectrum of mutations in many hematologic malignancies, including acute myeloid leukemia (AML), suggesting that combinations of agents will be required to treat these diseases effectively. Combinatorial approaches will also be critical for combating the emergence of genetically heterogeneous subclones, rescue signals in the microenvironment, and tumor-intrinsic feedback pathways that all contribute to disease relapse. To identify novel and effective drug combinations, we performed ex vivo sensitivity profiling of 122 primary patient samples from a variety of hematologic malignancies against a panel of 48 drug combinations. The combinations were designed as drug pairs that target nonoverlapping biological pathways and comprise drugs from different classes, preferably with Food and Drug Administration approval. A combination ratio (CR) was derived for each drug pair, and CRs were evaluated with respect to diagnostic categories as well as against genetic, cytogenetic, and cellular phenotypes of specimens from the two largest disease categories: AML and chronic lymphocytic leukemia (CLL). Nearly all tested combinations involving a BCL2 inhibitor showed additional benefit in patients with myeloid malignancies, whereas select combinations involving PI3K, CSF1R, or bromodomain inhibitors showed preferential benefit in lymphoid malignancies. Expanded analyses of patients with AML and CLL revealed specific patterns of ex vivo drug combination efficacy that were associated with select genetic, cytogenetic, and phenotypic disease subsets, warranting further evaluation. These findings highlight the heuristic value of an integrated functional genomic approach to the identification of novel treatment strategies for hematologic malignancies.