ABSTRACT
In the silkworm Bombyx mori and other insects, prothoracicotropic hormone (PTTH) plays a central role in controlling molting and metamorphosis by stimulating the prothoracic glands to synthesize and release the molting hormone ecdysone. Using an AcNPV (Autographa californica nucleopolyhedrovirus)-mediated transient gene transfer system, we identified a cis-regulatory element that participates in the decision to switch expression of PTTH on or off in PTTH-producing neurosecretory cells (PTPCs). The nucleotide sequence of this cis-regulatory element is similar to a cis-regulatory element that participates in direction of expression of diapause hormone-pheromone biosynthesis activating neuropeptide gene (DH-PBAN) (Shiomi et al., 2007). Furthermore, we found that B. mori Pitx (BmPitx), a bicoid-like homeobox transcription factor, binds the element and activates PTTH expression. Therefore, we propose that the cell-specific expression of two neuropeptide hormone genes, PTTH and DH-PBAN, is activated by the Pitx transcription factor, which may act as a pan-activator in the insect neuroendocrine system and in vertebrate pituitary cells.
Subject(s)
Bombyx/metabolism , Gene Expression Regulation , Homeodomain Proteins/metabolism , Insect Hormones , Insect Proteins/metabolism , Neuropeptides/metabolism , Protein Precursors/metabolism , Amino Acid Sequence , Animals , Base Sequence , Bombyx/genetics , Cloning, Molecular , Gene Transfer Techniques , Homeodomain Proteins/genetics , Insect Hormones/biosynthesis , Insect Hormones/genetics , Insect Proteins/genetics , Larva/genetics , Larva/metabolism , Microinjections , Molecular Sequence Data , Molting/genetics , Neuropeptides/genetics , Neurosecretory Systems/metabolism , Nucleopolyhedroviruses , Protein Precursors/genetics , Pupa/genetics , Pupa/metabolism , Transcription Factors/genetics , Transcription Factors/metabolismABSTRACT
Cancer of unknown primary site (CUP) is not a rare entity and accounts for 3-5% of all malignant neoplasias. CUPs are diagnosed with metastatic lesion so they are all in the advanced stage. Systemic chemotherapy is applied in many cases, but the ideal therapeutic strategy has not yet been determined. CUP shows much histological and therapeutic heterogeneity. Histologically, half of CUPs are adenocarcinoma and the rest are undifferentiated carcinomas. We analyzed the clinical and therapeutic characteristics 22 cases of CUP patients. Most CUP patients are found from lymph node swelling. There is no significant tendency as to the site of lymph node metastasis. Bone metastases are frequently encountered. It seems undifferentiated carcinomas are more responsive to chemotherapy. Chemo-sensitive patients are likely to have a longer life expectancy. In our experience all of the chemo-responsive cases are treated with platinum-based chemotherapy. Today several platinum-based combination chemotherapies are reported, but there is no large-scale randomized study. Because of its variety, individualized therapy may be ideal for CUP.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymph Nodes/pathology , Neoplasms, Unknown Primary/drug therapy , Neoplasms, Unknown Primary/mortality , Adenocarcinoma/drug therapy , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Bone Neoplasms/secondary , Carboplatin/administration & dosage , Combined Modality Therapy , Drug Administration Schedule , Etoposide/administration & dosage , Female , Fluorouracil/administration & dosage , Humans , Lymphatic Metastasis , Male , Middle Aged , Neoplasms, Unknown Primary/pathology , Paclitaxel/administration & dosage , Prognosis , Survival RateABSTRACT
BACKGROUND: Definitive chemoradiation with cisplatin (CDDP) and 5-fluorouracil (5FU) has been playing an important role in the treatment of esophageal cancer, but some patients are not curable or have recurrent lesions. However, few chemotherapeutic regimens are available for such patients. Docetaxel and nedaplatin are active for esophageal cancer. We conducted a dose-escalation study of docetaxel and nedaplatin as second line-chemotherapy after definitive chemoradiation in patients with relapsed or refractory squamous cell carcinoma of the esophagus after chemoradiation. METHODS: Nedaplatin was administered on day 1 and docetaxel was administered on days 1 and 15, every 4 weeks. Dose escalation was based on the dose-limiting toxicity (DLT) observed during the first cycle. RESULTS: Twelve patients were enrolled. At a docetaxel dose of 30 mg/m(2) and a nedaplatin dose of 80 mg/m(2), one grade 4 neutropenia occurred and caused one treatment break longer than 2 weeks, but there were few DLTs. At doses of 35 and 80 mg/m(2), respectively, two grade 4 neutropenias and one grade 2 thrombopenia occurred and caused three treatment breaks longer than 2 weeks. Therefore, the maximum tolerated dose was established at this dose level. Two grade 3 anorexias and one grade 3 nausea occurred, but other non-hematological toxicities were generally mild. Responses were seen in one-fourth of the 12 patients, including one complete remission. CONCLUSION: The recommended doses of docetaxel and nedaplatin were 30 and 80 mg/m(2), respectively. This combination could be a potential second-line treatment for this target population.
