Abstract: The present invention describes methods and compositions for improving the therapeutic efficacy of therapeutic agents previously limited by suboptimal therapeutic performance by either improving efficacy as monotherapy or reducing side effects. Such methods and compositions are particularly applicable to mustard-based alkylating agents such as uracil mustard and analogs, derivatives, or prodrugs thereof, including 6-methyluracil mustard and 6-ethyluracil mustard.

Abstract: The present disclosure provides botanicals and/or biotin or analogs thereof, that proliferate or reduce stem cell populations and activate or attenuate Wat/?-Catenin signaling and thus treat or prevent diseases related to signal transduction. In particular, the disclosure provides Botanicals and Biotin or analogs thereof, that proliferate or reduce stem cell populations and activate or attenuate Wnt/?-Catenin signaling in tissues expressing Wnt1OB including, adipose, adrenal, artery, blood, bone marrow, brain, breast, cervix, colon, esophagus, heart, intestine, kidney, liver, lung, muscle, ovary, pituitary, prostate, skin, spleen, testis, thyroid, uterus and vagina. The present compositions and methods are particularly suited to growing and melanizing hair.

Abstract: A method for treating diffuse intrinsic pontine glioma (DIPG) including administering a therapeutically effective quantity of an alkylating hexitol alone or in combination with another antiproliferative agent, such as an inhibitor of Wee1 tyrosine kinase, is disclosed.

Abstract: Methods for treating diffuse intrinsic pontine glioma (DIPG) comprising administration of a therapeutically effective amount of an alkylating hexitol (such as dianhydrogalacitol, diacetyldianhydrogalacitol, and dibromodulcitol) are disclosed. Such methods may further comprise administration of other anti-cancer agents. In preferred embodiments, the secondary anti-cancer agent is an inhibitor of Wee1 tyrosine kinase (such as adavosertib). Methods of treating malignancies in general comprising administration of a combination of an alkylating hexitol and an inhibitor of Wee1 tyrosine kinase are also disclosed.

Abstract: The present invention describes methods and compositions for improving the therapeutic efficacy of therapeutic agents previously limited by suboptimal therapeutic performance by either improving efficacy as monotherapy or reducing side effects. Such methods and compositions are particularly applicable to mustard-based alkylating agents such as uracil mustard and analogs, derivatives, or prodrugs thereof, including 6-methyluracil mustard and 6-ethyluracil mustard.

Abstract: The use of dianhydrogalactitol provides a novel therapeutic modality for the treatment of non-small-cell lung carcinoma (NSCLC) and ovarian cancer, as well as other types of malignancy, including brain metastases of NSCLC. Dianhydrogalactitol acts as an alkylating agent on DNA that creates N7 methylation. Dianhydrogalactitol is effective in suppressing the growth of cancer stem cells and is active against tumors that are refractory to temozolomide, cisplatin, and tyrosine kinase inhibitors; the drug acts independently of the MGMT repair mechanism. Dianhydrogalactitol can be used together with other anti-neoplastic agents and can possess additive or super-additive effects.

Abstract: The present invention describes methods and compositions for improving the therapeutic efficacy of therapeutic agents previously limited by suboptimal therapeutic performance by either improving efficacy as monotherapy or reducing side effects. Such methods and compositions are particularly applicable to mustard-based alkylating agents such as uracil mustard and analogs, derivatives, or prodrugs thereof, including 6-methyluracil mustard and 6-ethyluracil mustard.

Abstract: The use of dianhydrogalactitol provides a novel therapeutic modality for the treatment of malignancies of the central nervous system in pediatric patients, including glioblastoma multiforme (GBM) high grade glioma, and medulloblastoma. Dianhydrogalactitol acts as an alkylating agent on DNA that creates N7 methylation and that can induce double-stranded breaks in DNA. Dianhydrogalactitol is effective in suppressing the growth of cancer stem cells and is active against tumors that are refractory to temozolomide, cisplatin, and tyrosine kinase inhibitors; the drug acts independently of the MGMT repair mechanism. Dianhydrogalactitol can be used together with other anti-neoplastic agents (e.g. cisplatin) and can possess additive or super-additive effects.

Abstract: Methods for treating diffuse intrinsic pontine glioma (DIPG) comprising administration of a therapeutically effective amount of an alkylating hexitol (such as dianhydrogalacitol, diacetyldianhydrogalacitol, and dibromodulcitol) are disclosed. Such methods may further comprise administration of other anti-cancer agents. In preferred embodiments, the secondary anti-cancer agent is an inhibitor of Wee1 tyrosine kinase (such as adavosertib). Methods of treating malignancies in general comprising administration of a combination of an alkylating hexitol and an inhibitor of Wee1 tyrosine kinase are also disclosed.

Abstract: The use of dianhydrogalactitol provides a novel therapeutic modality for the treatment of glioblastoma multiforme and medulloblastoma. Dianhydrogalactitol acts as an alkylating agent on DNA that creates N7 methylation. Dianhydrogalactitol is effective in suppressing the growth of cancer stem cells and is active against tumors that are refractory to temozolomide; the drug acts independently of the MGMT repair mechanism.

Abstract: The use of dianhydrogalactitol provides a novel therapeutic modality for the treatment of glioblastoma multiforme and medulloblastoma. Dianhydrogalactitol acts as an alkylating agent on DNA that creates N7 methylation. Dianhydrogalactitol is effective in suppressing the growth of cancer stem cells and is active against tumors that are refractory to temozolomide; the drug acts independently of the MGMT repair mechanism.

Abstract: The use of dianhydrogalactitol provides a novel therapeutic modality for the treatment of glioblastoma multiforme and medulloblastoma. Dianhydrogalactitol acts as an alkylating agent on DNA that creates N7 methylation. Dianhydrogalactitol is effective in suppressing the growth of cancer stem cells and is active against tumors that are refractory to temozolomide; the drug acts independently of the MGMT repair mechanism.

Abstract: Methods and compositions suitable for the treatment of malignancies in subjects with a germline deletion polymorphism that blocks the activity of thymidine kinase inhibitors in triggering apoptosis in tumor cells or in subjects having a mutation in or a dysregulation of the AHI-1 gene are disclosed. These methods employ an alkylating hexitol derivative such as dianhydrogalactitol, a derivative or analog of dianhydrogalactitol, diacetyldianhydrogalactitol, a derivative or analog of diacetyldianhydrogalactitol, dibromodulcitol, and a derivative or analog of dibromodulcitol. The compositions can include such alkylating hexitol derivatives. The methods can further include administration of a BH3 mimetic, and the compositions can further include a BH3 mimetic. In subjects having a dysregulation of the AHI-1 gene, the methods can further include the administration of an agent modulating the expression or activity of the AHI-1 gene or AHI-1 protein, and the compositions can further include such an agent.

Abstract: Methods and compositions suitable for the treatment of malignancies such as recurrent glioma and progressive secondary brain tumor are disclosed. These methods employ a hexitol derivative such as dianhydrogalactitol, a derivative or analog of dianhydrogalactitol, diacetyldianhydrogalactitol, or a derivative or analog of diacetyldianhydrogalactitol. The compositions can include such hexitol derivatives.

Abstract: The present invention describes methods and compositions for improving the therapeutic efficacy of therapeutically active agents previously limited by suboptimal therapeutic performance by either improving efficacy as monotherapy or reducing side effects. Such methods and compositions are particularly applicable to therapeutically active agents selected from the group consisting of: (i) indirubin; (ii) an analog of indirubin; (iii) a derivative of indirubin or of an analog of indirubin; and (iv) a pharmaceutical composition comprising indirubin, an analog of indirubin, or a derivative of indirubin or of an analog of indirubin, especially meisoindigo.

Abstract: Methods and compositions employing dianhydrogalactitol or a derivative or analog of dianhydrogalactitol together with a vascular endothelial growth factor (VEGF) inhibitor or other anti-neoplastic agents can be used for treatment of glioma. In particular, methods and compositions according to the invention can decrease the invasiveness of gliomas. Further disclosed are methods of using the compositions for treating a malignancy that has failed a VEGF inhibitor treatment.

Abstract: Methods and compositions employing dianhydrogalactitol or a derivative analog of dianhydrogalactitol together with a p53 modulator, a PARP inhibitor, or topoisomerase inhibitor for treatment of malignancies are provided.

Abstract: A single input multiple output plasma control system includes a splitter that receives a single input and generates multiple outputs. Each output from the splitter is provided to a load. The splitter includes branch circuits connected between selected splitter outputs. The branch circuits control voltage, current, power, frequency, or phase between each branch to enable controlling a predetermined relationship between the voltage, current, power, impedance, frequency, or phase measured at each load.

Abstract: The use of dianhydrogalactitol provides a novel therapeutic modality for the treatment of non-small-cell lung carcinoma (NSCLC) and ovarian cancer, as well as other types of malignancy, including brain metastases of NSCLC. Dianhydrogalactitol acts as an alkylating agent on DNA that creates N7 methylation. Dianhydrogalactitol is effective in suppressing the growth of cancer stem cells and is active against tumors that are refractory to temozolomide, cisplatin, and tyrosine kinase inhibitors; the drug acts independently of the MGMT repair mechanism. Dianhydrogalactitol can be used together with other anti-neoplastic agents and can possess additive or super-additive effects.

Abstract: The present invention describes methods and compositions for improving the therapeutic efficacy of therapeutically active agents previously limited by suboptimal therapeutic performance by either improving efficacy as monotherapy or reducing side effects. Such methods and compositions are particularly applicable to therapeutically active agents selected from the group consisting of: (i) indirubin; (ii) an analog of indirubin; (iii) a derivative of indirubin or of an analog of indirubin; and (iv) a pharmaceutical composition comprising indirubin, an analog of indirubin, or a derivative of indirubin or of an analog of indirubin, especially meisoindigo.