1. A combination comprising:
(i) a compound of Structure (I):
or a pharmaceutically acceptable salt thereof; and
(ii) a compound of Structure (II):
or a pharmaceutically acceptable salt or solvate thereof.
2. A combination according to claim 1 where the compound of Structure (I) is in the form of a 2-amino-2-(hydroxymethyl)-1,3-propanediol salt and the compound of Structure (II) is in the form of a dimethyl sulfoxide solvate.
3. A kit comprising a combination according to claim 1 together with a pharmaceutically acceptable carrier or carriers.
4. A combination according to claim 1 where the amount of the compound of Structure (I) is selected from: about 5 mg, 25 mg and 100 mg, and that amount is administered once per day and the amount of the compound of Structure (II) is an amount selected from: about 0.5 mg, 1 mg and 2 mg, and that amount is administered once per day.
5. (canceled)
6. A method of treating cancer in a human in need thereof which comprises the in vivo administration of a therapeutically effective amount of
2-methyl-1-{2-methyl-3-(trifluoromethyl)phenylmethyl}-6-(4-morpholinyl)-1H-benzimidazole-4-carboxylic acid 2-amino-2-(hydroxymethyl)-1,3-propanediol salt, and
N-{3-3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)6,8-dimethy;-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido4,3-dpyrimidin-1-ylphenyl}acetamide, or a pharmaceutically acceptable salt or solvate thereof, to such human, wherein the combination is administered within a specified period, and wherein the combination is administered for a duration of time.
7. A method of treating cancer in a human in need thereof according to claim 6, wherein a specified period is within 24 hours.
8. A method according to claim 7, wherein
2-methyl-1-{2-methyl-3-(trifluoromethyl)phenylmethyl}-6-(4-morpholinyl)-1H-benzimidazole-4-carboxylic acid 2-amino-2-(hydroxymethyl)-1,3-propanediol salt is administered once per day in an amount selected from about 5 mg, 25 mg and 100 mg, and
N-{3-3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)6,8-dimethy;-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido4,3-dpyrimidin-1-ylphenyl}acetamide dimethyl sulfoxide is administered once per day in an amount selected from about 0.5 mg, about 1 mg and about 2 mg, suitably about 2 mg, by weight of the un-solvated compound.
9. A method according to claim 8 wherein the cancer is selected from: breast cancer, inflammatory breast cancer, ductal carcinoma, lobular carcinoma, colon cancer, pancreatic cancer, insulinoma, adenocarcinoma, ductal adenocarcinoma, adenosquamous carcinoma, acinar cell carcinoma, glucagonoma, melanoma, metastatic melanoma, lung cancer, small cell lung cancer, non-small cell lung cancer, squamous cell carcinoma, adenocarcinoma, and large cell carcinoma, brain (gliomas), glioblastomas, astrocytomas, glioblastoma multiforme, Bannayan-Zonana syndrome, Cowden disease, Lhermitte-Duclos disease, Wilm’s tumor, Ewing’s sarcoma, Rhabdomyosarcoma, ependymoma, medulloblastoma, head and neck, kidney, liver, melanoma, ovarian, pancreatic, adenocarcinoma, ductal adenocarcinoma, adenosquamous carcinoma, acinar cell carcinoma, glucagonoma, insulinoma, prostate, sarcoma, osteosarcoma, giant cell tumor of bone, thyroid, lymphoblastic T cell leukemia, chronic myelogenous leukemia, chronic lymphocytic leukemia, hairy-cell leukemia, acute lymphoblastic leukemia, acute myelogenous leukemia, chronic neutrophilic leukemia, acute lymphoblastic T cell leukemia, plasmacytoma, Immunoblastic large cell leukemia, mantle cell leukemia, multiple myeloma, megakaryoblastic leukemia, multiple myeloma, acute megakaryocytic leukemia, promyelocytic leukemia, erythroleukemia, malignant lymphoma, hodgkins lymphoma, non-hodgkins lymphoma, lymphoblastic T cell lymphoma, Burkitt’s lymphoma, follicular lymphoma, neuroblastoma, bladder cancer, urothelial cancer, vulval cancer, cervical cancer, endometrial cancer, renal cancer, mesothelioma, esophageal cancer, salivary gland cancer, hepatocellular cancer, gastric cancer, nasopharangeal cancer, buccal cancer, cancer of the mouth, GIST (gastrointestinal stromal tumor) and testicular cancer.
10. A method according to claim 8 wherein the cancer selected from ovarian, breast, pancreatic and prostate.
11. A method of treating or lessening the severity of cancer that is either wild type or mutant for BRAF, KRAS, NRAS, HRAS, SOS1, NF1, EGFR, ErbB2, c-Kit, PDGFR, or ErbB-2 genes or have overexpression of EGFR or ErbB2 protein, in a human in need thereof which comprises the in vivo administration of a therapeutically effective amount of
2-methyl-1-{2-methyl-3-(trifluoromethyl)phenylmethyl}-6-(4-morpholinyl)-1H-benzimidazole-4-carboxylic acid, or a pharmaceutically acceptable salt thereof, and
N-{3-3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)6,8-dimethy;-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido4,3-dpyrimidin-1-ylphenyl}acetamide, or a pharmaceutically acceptable salt or solvate thereof, to such human, wherein the combination is administered within a specified period, and wherein the combination is administered for a duration of time.
12. A method according to claim 11 wherein the cancer selected from ovarian, breast, pancreatic and prostate.
13. A method according to claim 11 wherein a specified period is within 24 hours.
14. A method of treating cancer in a human in need thereof according to claim 6, wherein a specified period is within 24 hours and the duration of time is 7 days.
15. A method of treating cancer in a human in need thereof according to claim 6, wherein a specified period is within 24 hours and the duration of time is 14 days.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. An endoscope system comprising:
an endoscope having a channel;
an insertion-section flexibly inserted into the channel;
a treating section, disposed at a distal end of the insertion-section, for treating a target section;
an driving-section, making contact with the insertion-section, for driving the insertion-section with respect to predetermined directions; and
a pivoting section for directing the driving-section toward a first direction or a second direction, wherein
the first direction indicates the direction for driving the insertion-section along an axial line of the insertion-section, and
the second direction indicates the direction for rotating the insertion-section around the axial line.
2. An endoscope system according to claim 1, wherein the pivoting section directs the driving-section from 0 to 90 degrees with respect to the axial line.
3. An endoscope system according to claim 1, wherein the driving-section has a plurality of rollers making contact with the insertion-section.
4. An endoscope system according to claim 3, wherein the driving-section comprises:
the plurality of rollers; and
a switching section for changing the rotational direction of at least one of the rollers in accordance with the pivoted direction of the rollers.
5. An endoscope system according to claim 3, wherein protrusions are formed on outer surfaces of the rollers.
6. An endoscope system according to claim 1, further comprising:
a housing for pivotably supporting the driving-section; and
a guide member, fixed in the housing, through which the insertion-section is inserted, the guide member having apertures through which the driving-section making contact with the insertion-section.
7. An endoscope system according to claim 1, wherein protrusions and grooves are alternately provided on a surface of the insertion-section, the surface making contact with the driving-section.
8. An endoscope system according to claim 1, wherein a cross section of a part of the insertion-section is polygonal, the part making contact with the driving-section.
9. An endoscope system according to claim 3, wherein each pivoting section has a pivoting shaft having a pivoting axial line, the pivoting axial line being disposed on a line extending along radial directions of the rollers, and passes through a section in which the rollers making contact with the insertion-section.
10. An endoscope system, comprising:
an endoscope having a channel;
an insertion-section flexibly inserted into the channel;
a treating section, disposed on a distal end of the insertion-section, for treating a target section, the treating section being manipulated by a wire disposed in the insertion-section;
an driving-section for driving the insertion-section with respect to predetermined directions, the driving-section making contact with the insertion-section;
a wire driving section for driving the wire with respect to the predetermined directions; and
a pivoting section for directing the driving-section and the wire-driving section with respect to first and second directions, wherein the first direction indicates the direction for driving the driving-section and the wire along the axial lines thereof, and
the second direction indicates a the direction for rotating the insertion-section and the wire around.
11. An endoscope system according to claim 10, further comprising a tube connected to a proximal end of the insertion-section, wherein the wire is inserted in the tube, and the tube make contact with the wire-driving section.
12. An endoscope system according to claim 10, further comprising a control section for controlling the driving-section and the wire-driving section, wherein the control section has selective modes, the modes including: a first mode in which the driving-section and the wire-driving section are driven synchronously; and a second mode in which the wire-driving section is driven while the driving-section is stopped.
13. An endoscope system comprising:
an endoscope having a channel;
a treating section, disposed at a distal end of the insertion-section, for treating a target section;
an driving-section, making contact with the insertion-section, for driving the insertion-section along an axial line of the channel; and
a rotative-connective section for connecting the driving-section and the endoscope so that the driving-section is rotative around the axial line of the channel.