Disclosed herein are methods for treating a cancer comprising: a. administering a Btk inhibitor to a subject sufficient to result in an increase or appearance in the blood of a subpopulation of lymphocytes defined by immunophenotyping; b. determining the expression profile of one or more biomarkers from one or more subpopulation of lymphocytes; and c. administering a second agent based on the determined expression profile.

Provided herein are compositions comprising substantially non-viable Gram-negative bacterial organisms that have a substantial reduction in endotoxin activity and/or pyrogenicity and methods for treating a cancer using the same. Also provided are methods for treating cancer provided herein, comprising administering to a mammal diagnosed with cancer, substantially non-viable Gram-negative bacteria having a substantial reduction in endotoxin activity and/or pyrogenicity, in an amount sufficient to inhibit growth or metastasis of the cancer. An additional method is provided comprising administering viable or non-viable Gram-negative bacterial organisms that have a genetic defect that results in a substantial loss of lipopolysaccharide within the outer membrane of the bacteria. Further provided are methods for reducing endotoxin activity and/or pyrogenicity in Gram-negative bacteria comprising treatment with polymyxin and glutaraldehyde.

A medicament characterized in that (A) a compound represented by the formula (I): ##STR00001##
its pharmaceutically acceptable salt, or a solvate thereof,
wherein P is hydrogen or a group to form a prodrug; A.sup.1 is CR.sup.1AR.sup.1B, S or O; A.sup.2 is CR.sup.2AR.sup.2B, S or O; A.sup.3 is CR.sup.3AR.sup.3B, S or O; A.sup.4 is each independently CR.sup.4AR.sup.4B, S or O; the number of hetero atoms among atoms constituting the ring which consists of A.sup.1, A.sup.2, A.sup.3, A.sup.4, nitrogen atom adjacent to A.sup.1 and carbon atom adjacent to A.sup.4 is 1 or 2; R.sup.1A and R.sup.1B are each independently hydrogen, halogen, alkyl or the like; R.sup.2A and R.sup.2B are each independently hydrogen, halogen, alkyl, or the like; R.sup.3A and R.sup.3B are each independently hydrogen, halogen, alkyl, or the like; R.sup.4A are each independently hydrogen, halogen, alkyl, or the like; R.sup.4B are each independently hydrogen, halogen, alkyl, or the like; R.sup.3A and R.sup.3B may be taken together with an adjacent carbon atom to form non-aromatic carbocycle or non-aromatic heterocycle; n is any integer of 1 to 2; and R.sup.1 is ##STR00002##
or the like,
is combined with (B) compound(s) having an anti-influenza activity, its pharmaceutically acceptable salt or a solvate thereof and/or an antibody having anti-influenza activity, is useful for treating or preventing influenza.

A medicament characterized in that (A) a compound represented by the formula (I): ##STR00001##
its pharmaceutically acceptable salt, or a solvate thereof,
wherein P is hydrogen or a group to form a prodrug; A.sup.1 is CR.sup.1AR.sup.1B, S or O; A.sup.2 is CR.sup.2AR.sup.2B, S or O; A.sup.3 is CR.sup.3AR.sup.3B, S or O; A.sup.4 is each independently CR.sup.4AR.sup.4B, S or O; the number of hetero atoms among atoms constituting the ring which consists of A.sup.1, A.sup.2, A.sup.3, A.sup.4, nitrogen atom adjacent to A.sup.1 and carbon atom adjacent to A.sup.4 is 1 or 2; R.sup.1A and R.sup.1B are each independently hydrogen, halogen, alkyl or the like; R.sup.2A and R.sup.2B are each independently hydrogen, halogen, alkyl, or the like; R.sup.3A and R.sup.3B are each independently hydrogen, halogen, alkyl, or the like; R.sup.4A are each independently hydrogen, halogen, alkyl, or the like; R.sup.4B are each independently hydrogen, halogen, alkyl, or the like; R.sup.3A and R.sup.3B may be taken together with an adjacent carbon atom to form non-aromatic carbocycle or non-aromatic heterocycle; n is any integer of 1 to 2; and R.sup.1 is ##STR00002##
or the like,
is combined with (B) compound(s) having an anti-influenza activity, its pharmaceutically acceptable salt or a solvate thereof and/or an antibody having anti-influenza activity, is useful for treating or preventing influenza.

Disclosed are compounds of Formula I:

##STR00001##

or a pharmaceutically acceptable salt, a solvate, a tautomer, a stereoisomer or a deuterated analog thereof, wherein R.sup.1, R.sup.2, R.sup.3, A, L, and G are as described in any of the embodiments described in this disclosure; compositions thereof; and uses thereof.

Disclosed are compounds of Formula I:

##STR00001##

or a pharmaceutically acceptable salt, a solvate, a tautomer, a stereoisomer or a deuterated analog thereof, wherein R.sup.1, R.sup.2, R.sup.3, A, L, and G are as described in any of the embodiments described in this disclosure; compositions thereof; and uses thereof.

Disclosed herein is a recombinant nucleic acid, comprising: a mitochondrial targeting sequence; a mitochondrial protein coding sequence, wherein said mitochondrial protein coding sequence encodes a polypeptide comprising a mitochondrial protein; and a 3′UTR nucleic acid sequence. Also disclosed is a pharmaceutical composition comprising the recombinant nucleic acid and a method of treating Leber's hereditary optic neuropathy (LHON) using the pharmaceutical composition.

Disclosed herein is a recombinant nucleic acid, comprising: a mitochondrial targeting sequence; a mitochondrial protein coding sequence, wherein said mitochondrial protein coding sequence encodes a polypeptide comprising a mitochondrial protein; and a 3′UTR nucleic acid sequence. Also disclosed is a pharmaceutical composition comprising the recombinant nucleic acid and a method of treating Leber's hereditary optic neuropathy (LHON) using the pharmaceutical composition.

The invention relates to a compound of General Formula (I): wherein R1, R2, R3, R4 and R5 are as defined herein. Compounds and compositions comprising the same exhibit high serum stability and potent activation of the γδ T-cell immune response, so are suitable for use in immunotherapy. The invention also relates to methods of immunotherapy using the compounds of General Formula (I).

##STR00001##

The invention provides derivatives of cyclopamine having the following formula: ##STR00001##