[Granulocyte-colony stimulating factor-producing urothelial carcinoma of right renal pelvis : a case report].

A 78-year-old female patient with fever and general malaise was referred to our hospital. Laboratory examination showed the marked elevation of leukocyte and serum granulocyte-colony stimulating factor (GCSF) concentration without any infectious sign. A computed tomography scan demonstrated irregular enhanced mass of the right kidney with liver metastasis. The pathological findings of the needle biopsy was high-grade urothelial cancer with positive staining for G-CSF antibody. Systemic chemotherapy with gemcitabine and cisplatin was administered. The patient showed a partial response and the serum G-CSF level was normalized after 1 course of chemotherapy. After four courses of chemotherapy, the extent of liver metastasis increased and the G-CSF concentration became elevated. Although combined chemotherapy with paclitaxel and gemcitabine was administered, the patient died 7 months after her first visit.

Melanoma-Targeted Chemothermotherapy and In Situ Peptide Immunotherapy through HSP Production by Using Melanogenesis Substrate, NPrCAP, and Magnetite Nanoparticles.

Exploitation of biological properties unique to cancer cells may provide a novel approach to overcome difficult challenges to the treatment of advanced melanoma. In order to develop melanoma-targeted chemothermoimmunotherapy, a melanogenesis substrate, N-propionyl-4-S-cysteaminylphenol (NPrCAP), sulfur-amine analogue of tyrosine, was conjugated with magnetite nanoparticles. NPrCAP was exploited from melanogenesis substrates, which are expected to be selectively incorporated into melanoma cells and produce highly reactive free radicals through reacting with tyrosinase, resulting in chemotherapeutic and immunotherapeutic effects by oxidative stress and apoptotic cell death. Magnetite nanoparticles were conjugated with NPrCAP to introduce thermotherapeutic and immunotherapeutic effects through nonapoptotic cell death and generation of heat shock protein (HSP) upon exposure to alternating magnetic field (AMF). During these therapeutic processes, NPrCAP was also expected to provide melanoma-targeted drug delivery system.

[Hyperthemia enhances activated lymphocytes and molecular target therapy].

We already informed that a combination therapy of hyperthermia and activated lymphocytes therapy reduced the tumor growth and lung metastasis synergistically in mice model. In this study we treated mice inoculated LLC tumors with hyperthermia or molecular target drugs (erlotinib 25 mg/kg/day and sorafenib 10 mg/kg/day). Both of hyperthermia and molecular target therapy reduced not only tumor growth but also lung metastasis. And a combination therapy of hyperthermia and molecular target therapy reduced more of the tumor growth and lung metastasis synergistically. The expression of HER2 and VEGFR was reduced by hyperthermia and molecular target drugs. Apoptosis was enhanced by hyperthermia and molecular target drugs synergistically.

[Hyperthermic immuno-cellular therapy-basic and clinical study].

BASIC: We treated mice inoculated LLC tumors with hyperthermia or activated lymphocytes. Both of hyperthermia and activated lymphocytes therapy reduced not only a tumor growth but also lung metastasis. And a combination therapy of hyperthermia and activated lymphocytes therapy reduced more of the tumor growth and lung metastasis synergistically. CLINICAL: We proceeded with hyperthermia (HT) for 472 cancer patients and activated lymphocytes (CAT) therapy for 384 patients and dendritic cell (DC) therapy for 94 patients. Two-hundred-thirty-eight patients of them underwent a combination therapy with hyperthermia and CAT therapy. And 92 patients received a combination therapy with hyperthermia and DC therapy. We proceeded with hyperthermia or immunotherapy for 526 cancer patients. And we have 67 clinical benefit cases including 8 complete response (CR) cases. These basic and clinical results indicate an effectiveness of a combination therapy with hyperthermia and cellular-immunotherapy for cancer patients.

Clinical effect of bisphosphonate and vitamin D on osteoporosis: reappraisal of a multicenter double-blind clinical trial comparing etidronate and alfacalcidol.

As inhibitors of bone resorption, bisphosphonates and vitamin D derivatives have been extensively used for the treatment of osteoporosis in various parts of the world, but the clinical effects of these two groups of agents have rarely been compared in detail. A multicenter, prospective, double-blind controlled study was started comparing the effects of etidronate and alfacalcidol (1-alpha-hydroxycholecalciferol) in 414 patients with established osteoporosis from 36 centers. Among these patients, 135 were given 400 mg etidronate daily at bedtime for 2 weeks followed by 10 weeks off treatment, and this cycle was repeated four times along with a placebo indistinguishable from the alfacalcidol capsule daily throughout the 48 weeks of study (Group A, High Dose Etidronate Group). In 133 patients, 200 mg etidronate was used instead of 400 mg (Group B, Low Dose Etidronate Group). In 138 patients, 1 microg alfacalcidol was given daily throughout the 48-week study period along with a placebo indistinguishable from the etidronate tablet in four separate periods of 2 weeks (Group C, Control Group). Dual-energy X-ray absorptiometry of the lumbar spine (L2-L4) was performed before the beginning of the study and every 12 weeks thereafter. Changes in spinal deformity were also assessed based on the lateral thoracic and lumbar spine X-ray films taken before and after the study. The lumbar spine bone mineral density (BMD) changes were +3.4% +/- 0.6% (mean +/- SEM) in Group A, +2.4% +/- 0.5% in Group B, and -0.5% +/- 0.4% in Group C, the former two being significantly higher than the last. New occurrence of spinal compression fracture was also significantly reduced in Group A compared to Group C. In patients without previous fracture at entry, incident fracture was 10.2% in Group C, but 0% in Groups A and B. In patients with prevalent fracture at entry, corresponding figures were 21.5% (Group C), 12.0% (Group A), and 13.2% (Group B), respectively. Alfacalcidol maintained lumbar spine BMD, preventing a decrease for 48 weeks, and etidronate significantly increased it further, demonstrating its usefulness in the treatment of established osteoporosis.

Multicenter study investigating the postoperative progression of ossification of the posterior longitudinal ligament in the cervical spine: a new computer-assisted measurement.

OBJECT: Ossification of the posterior longitudinal ligament (OPLL) often progresses after surgery, and this may cause late-onset neurological deterioration. There have been few studies, however, to clarify any correlation between progression and clinical outcome, partly because of the lack of studies involving reliable and reproducible methods by which detection of progression is made possible. The authors conducted a multicenter study to investigate the occurrence of postoperative progression and to elucidate the possible risk factors in a large-scale patient population, and a novel computer-assisted measurement method was used to provide the basis for future clinical studies. METHODS: The authors analyzed lateral plain radiographs obtained immediately and at 1 and 2 years after surgery in 131 patients who underwent posterior decompression at 13 institutions. The x-ray films were transformed via scanner into digital images; the length and thickness of ossifications were measured using a new computer-assisted measurement system, and the incidence of progression was determined. Odds ratios for progression according to age group and types of OPLL were determined and compared to elucidate significant risk factors of progression. CONCLUSIONS: This is the first multicenter study to investigate the incidence of OPLL progression after posterior decompression by using a standardized measurement method. The rate of postoperative progression at 2 years was 56.5%, which was comparable with results reported in other studies. Progression occurred more frequently in younger-age rather than in older-age patient populations at both 1 and 2 years postoperatively. Mixed-type and continuous-type OPLL progressed more frequently than the segmental-type lesion at 2 years. The results of the present study could serve as basis for future studies to assess the efficacy of drug therapy to prevent OPLL progression.