The hypothalamus to brainstem circuit suppresses late-onset body weight gain.

Body weight (BW) is regulated in age-dependent manner; it continues to increase during growth period, and reaches a plateau once reaching adulthood. However, its underlying mechanism remains unknown. Regarding such mechanisms in the brain, we here report that neural circuits from the hypothalamus (paraventricular nucleus: PVN) to the brainstem (dorsal vagal complex: DVC) suppress late-onset BW gain without affecting food intake. The genetic suppression of the PVN-DVC circuit induced BW increase only in aged rats, indicating that this circuit contributes to suppress the BW at a fixed level after reaching adulthood. PVN neurons in the hypothalamus were inactive in younger rats but active in aged rats. The density of neuropeptide Y (NPY) terminal/fiber is reduced in the aged rat PVN area. The differences in neuronal activity, including oxytocin neurons in the PVN, were affected by the application of NPY or its receptor inhibitor, indicating that NPY is a possible regulator of this pathway. Our data provide new insights into understanding age-dependent BW regulation.

[Treating Side Effects of FOLFIRINOX--A Study of the Effect of Hange-Shashin-To on Preventing Diarrhea].

OBJECTIVES: FOLFIRINOX is an effective therapy for unresectable advanced pancreatic cancer. However, FOLFIRINOX has side effects of blood and gastrointestinal toxicity. Diarrhea, one of the side effects of CPT-11, sometimes becomes serious. We studied whether Hange-shashin-to could prevent diarrhea caused by CPT-11. METHODS: Seven patients who were diagnosed with unresectable pancreatic cancer, either Stage Ⅳor recurrent disease, were enrolled. They took 2.5 g of Hange-shashin-to before each meal starting one day before FOLFIRINOX, and continued taking it for one week. We examined the occurrence of diarrhea by using CTCAE retrospectively. RESULTS: The median age was 61 years. The median number of chemotherapy courses was 4. The frequency of diarrhea was lower, compared to the results of ACCORD11 trial and the domestic phaseⅡ clinical trials. In addition, Grade 3 or more serious diarrhea was not observed, even in the patients with genetic polymorphisms of UGT1A1. CONCLUSION: The incidence of diarrhea in patients treated with Hange-shashin-to in our department was lower compared to the ACCORD11 trial and domestic phase Ⅱ clinical trials. Hange-shashin-to is useful to allay the severity of diarrhea caused by CPT-11 in FOLFIRINOX therapy.

[PSK decreased FOLFOX4-induced peripheral neuropathy and bone marrow suppression in patients with metastatic colorectal cancer].

FOLFOX4 has been proven to be effective for metastatic colorectal cancer and is now used as a postoperative adjuvant therapy. However, adverse effects such as cold-sensitive paresthesia and bone marrow suppression are common, and this may necessitate a change of chemotherapy regimen even though FOLFOX is effective. PSK, a polysaccharide derived from mushrooms, has been developed in Japan as an immune-enhancing agent, and is widely used in patients with gastric, colorectal and pulmonary cancer. PSK has also been reported to decrease some adverse effects of chemotherapy. FOLFOX4 combined with PSK was administered to patients with metastatic colorectal cancer and the results were evaluated. Eight cycles of FOLFOX4 and PSK (3.0 g/day, po) were given to 25 patients with metastatic (19 hepatic, 3 pulmonary and 3 peritoneal) colorectal cancer. There was no CR (0%), while PR, SD and PD were 48, 36 and 16%, respectively. The response rate was 48%, and the disease control rate was 84%. There were significantly lower frequencies of adverse effects in comparison with published data. Grades 1 and 3 neutropenia occurred in 48 and 24%, respectively, of the patients; grades 1 and 3 nausea in 48 and 4%; and grades 1, 2 and 3 sensory neurotoxicity in 52, 4 and 0%. No patient dropped out due to adverse effect in this study. PSK plus FOLFOX4 seemed to be as effective as FOLFOX4 monotherapy as has been published, and significantly less toxic. These results suggest that this combination therapy may be more effective than FOLFOX4 monotherapy when given over a longer period, with a lower incidence of adverse effects.

[A case of liver metastases from cecal cancer successfully treated with fluorouracil and folinic acid (UFT/LV)].

A 76-year-old man had undergone a right hemicolectomy for cecal cancer. Oral UFT (450 mg/day) administration alone was started 2 months following the operation. From a CT scan of the abdomen performed 3 months postoperatively, he was diagnosed with liver metastasis. Because the liver metastasis had progressed, combination oral administration of UFT+LV was started (UFT 450 mg/day, LV 75 mg/day, 4 weeks of therapy followed by a 1-week treatment break). After 1 cycle, a good partial response of that lesion was achieved. The pulmonary metastasis had almost disappeared to within normal limits. In conclusion, this treatment was very safe and effective.

[A patient with metastatic breast cancer associated with retention of pleural effusion with no response to both CMF and exemestane, whose life was saved by high-dose toremifene].

The patient was a 70-year-old woman, who became aware of a mass in her right breast in 2001, but left it untreated. On March 10, 2003, she visited a nearby doctor with the chief complaint of dyspnea. Since a large painful mass was palpable in the right breast, advanced right breast cancer was suspected, and the patient was referred to our department. Examination revealed the presence of right axillary lymph node metastasis, left pleural effusion, and left atelectasis, and the patient was admitted to our hospital on an emergency basis. Two cycles of CMF were begun on April 2, but CT indicated NC to PD. Therefore, exemestane (EXE, 25 mg/day), was administered on May 13. While the size of the primary lesion was partially decreased, the tumor marker levels were increasing markedly. Administration of EXE was therefore discontinued, and toremifene (TOR, 120 mg/day), was begun. The systemic condition began to improve one month after the start of TOR administration. Two months later, the primary lesion had decreased in size. At after 9 months of TOR treatment, the size of the primary lesion and the tumor marker levels continued to decrease, and both the left pleural effusion and the left atelectasis disappeared.