[A case of interstitial pneumonia induced by CPT-11 for local recurrence of rectal cancer].

A 60-year-old man underwent total pelvic exenteration for rectal cancer and urinary bladder invasion.He received adjuvant chemotherapy with S-1 and PSK.Because of local recurrence in the 4th postoperative month, he underwent FOLFIRI therapy followed by mFOLFOX6 therapy.After an adverse reaction occurred for OHP, CPT-11 therapy was performed.After 1 course of CPT-11 therapy, he complained of dyspnea and chest pain.We suspected drug-induced interstitial pneumonia, and stopped chemotherapy.He still complained dyspnea, and was treated with PSL.Once dyspnea improved, he gradually deteriorated and was admitted to the hospital.He was given oxygen and steroid pulse therapy, but died of respiratory failure.

[A case of unresectable and multiple advanced primary cancers of the stomach and rectosigmoid colon with hepatic metastases successfully treated with FOLFIRI for local control of a gastric lesion].

The patient was a 59-year-old man who was hospitalized at our department for intestinal obstruction. Contrast enhanced abdominal CT showed a rectosigmoid tumor invading the left pelvic wall and multiple metastatic hepatic tumors. Colonoscopy showed a type-2 cancer in the rectosigmoid region. The patient underwent sigmoid colostomy 3 days after admission. Postoperative upper gastrointestinal endoscopy showed a type 3 cancer in the fornix. From the above findings, the patient was diagnosed with unresectable gastric and rectosigmoid cancers with multiple hepatic metastases, and systemic chemotherapy was initiated. The first line treatment was two courses of S-1, but it was discontinued due to PD. FOLFIRI was begun as the second line treatment. After 5 courses of FOLFIRI, upper gastrointestinal endoscopy showed a marked reduction in tumor size. Twelve courses of FOLFIRI chemotherapy were performed in total. Subsequently, 11 courses of mFOLFOX6 and 1 course of RPMI were performed, but the patient died from carcinomatous peritonitis. However, the gastric lesion had been controlled well after the second line treatment. The findings of the present study suggested that FOLFIRI could be an effective treatment for unresectable multiple advanced cancers of the stomach and colorectal cancer.

[A case of unresectable multiple hepatic metastases from colorectal cancer successfully treated with IRIS (S-1, CPT-11) therapy].

In a patient with multiple liver metastases of colorectal cancer whose tumor response had been achieved by 5-FU hepatic arterial infusion, a catheter for arterial infusion chemotherapy was occluded resulting in re-elevation of tumor marker levels. For this reason, a second-line IRIS therapy using S-1 and CPT-11 was started. IRIS therapy reduced tumor marker levels to a degree greater than that of previously achieved with 5-FU hepatic arterial infusion, and a diagnostic imaging allowed a judgment of partial response. Although a ratio of liver tumor volume to liver volume was 57% on admission of this patient, the ratio was reduced to 16% by the 14th course of 5-FU hepatic arterial infusion immediately before the catheter was occluded. The ratio was 18% after the 7th course of IRIS therapy, and the diagnostic imaging showed a partial response. Hepatic arterial infusion therapy is one of the treatment methods characterized by a lower incidence of adverse reactions, relatively low cost, and expectation of high anti-tumor efficacy as compared to chemotherapy such as FOLFIRI. IRIS therapy does not require a port insertion and it costs about a half of FOLFIRI therapy. When used as a second-line therapy for unresectable colorectal cancer, IRIS therapy has demonstrated non-inferiority compared to FOLFIRI in a phase III clinica (l FIRIS) study.

[A long-term survival case of local recurrence of breast cancer treated with combined modality therapy].

The case was a 70-year-old woman. In 1997, the patient underwent pectoral muscle-preserving mastectomy and axillary/subclavicular lymph node dissection for the treatment of right breast cancer. Histological diagnosis was invasive ductal carcinoma (T2, N2, M0, Stage IIIA). She received a combination therapy with TAM and UFT for 5 years postoperatively. Because tumor recurrence occurred in right axillary lymph nodes in the 9th postoperative year, the patient underwent resection of these lymph nodes followed by 6 cycles of AC-based chemotherapy. Multiple lung metastases occurred in the 10th postoperative year, and then, the patient received 8 cycles of DOC-based chemotherapy. In the 11th postoperative year, a mass appeared again in the right axilla, and 6 cycles of capecitabine-based chemotherapy was administered. In the 12th postoperative year, pulmonary metastasis was in progression and an increased right axillary mass were noted. Thus, the specimen extirpated in 2006 was examined again, revealing negative ER, negative PgR and positive HER2. Six cycles of combined trastuzumab+PTX therapy were administered. Lung metastasis decreased in size, allowing a judgment of partial response. Because the right axillary mass had grown to 10 cm, and the patient's QOL was reduced, it was extirpated. The patient is scheduled to receive a postoperative radiotherapy, followed by resumption of chemotherapy.

[A case of stage IV breast cancer responding to S-1 therapy after FEC and PTX therapies].

In November 2005, a 34-year-old female presented to our department with a bleeding tumor on her right breast. She noticed the tumor approximately two years ago but she left it untreated. An exposed tumor was observed with a diameter of approximately 8 cm located in the right breast. It was diagnosed as invasive ductal carcinoma by biopsy (ER (+), PgR (+), and HERS2: 1 +). The imaging showed multiple metastases to the bilateral lungs, right axillary lymph node, mediastinal lymph node and sternal. The diagnosis was made as right breast cancer (T4c, N3c, M1, and stage IV). The patient received 4 courses of FEC therapy and 4 courses of PTX therapy. The patient had a partial response (PR). However, tumor markers were elevated in September 2006. Thus, an administration of S-1 was initiated. The size of the tumor shown in the imaging was reduced, and the patient had a PR. Since December 2008, tumor markers have been elevated again. However, the patient has had SD in the imaging and S-1 administrations have been continued. A total of 24 courses have been performed to the present time, and the patient's conditions have not been aggravated in approximately 3 years and 5 months. She has maintained a good QOL and is being followed up on an outpatient basis. S-1 administrations can be an effective treatment for advanced breast cancer resistant to anthracycline and taxane when considering a satisfactory QOL of patients.

Trehalose inhibits inflammatory cytokine production by protecting IkappaB-alpha reduction in mouse peritoneal macrophages.

OBJECTIVE: The aim of this study was to examine whether trehalose, a disaccharide, could inhibit Porphyromonas gingivalis (P. gingivalis) lipopolysaccharide (LPS)-enhanced production of inflammatory cytokines in mouse peritoneal macrophages. DESIGN: Mouse peritoneal macrophages were treated with trehalose and stimulated with P. gingivalis LPS. Interleukin-1beta (IL-1beta) and tumour necrosis factor-alpha (TNF-alpha) levels in the culture supernatant were measured by ELISA. The mRNA levels of the cytokines in macrophages were analysed by semi-quantitative RT-PCR. DNA and protein synthesis were measured by incorporation of [(3)H] thymidine or [(14)C] praline into mouse peritoneal macrophages. IkappaB-alpha reductions were assessed by western blot. RESULTS: Treatment with trehalose suppressed LPS-induced IL-1beta and TNF-alpha production and downregulated transcription of these cytokines. Furthermore, trehalose inhibited LPS-induced reduction of IkappaB-alpha. In addition, we also observed expression of the trehalose receptor (T1R3) in mouse peritoneal macrophages. CONCLUSION: These results may suggest that trehalose inhibits LPS-induced production of IL-1beta and TNF-alpha in mouse peritoneal macrophages by inhibiting degradation of IkappaB-alphavia the trehalose receptor T1R3.

Serum interleukin-12 levels in patients with gastric cancer.

PURPOSE: To evaluate the immunological status of patients with gastric cancer before surgery, we investigated the relationship between serum interleukin-12 (IL-12) levels and clinicopathological factors. METHODS: We measured serum IL-12 levels in 127 patients with gastric cancer and 35 healthy controls, by a sandwich enzyme-linked immunosorbent assay using the Human IL-12 +p40 Immunoassay kit. RESULTS: The serum IL-12 levels in the patients with gastric cancer were significantly higher than those of the healthy controls (P < 0.05). There were no significant differences in disease stage or gross appearance among the cancer groups, but the serum IL-12 levels in patients with T4 disease were significantly lower than those in patients with T1, T2, or T3 (P < 0.01). There were no significant differences in serum IL-12 levels between patients with and those without lymph node, liver, or peritoneal metastasis. The serum IL-12 levels in patients with distant metastasis were significantly lower than those in patients without distant metastasis (P < 0.02). There were no significant differences in the serum IL-12 levels according to classification by histopathological findings. Analysis with the linear correlation coefficient showed no significant correlation between serum IL-12 and serum carcinoembryonic antigen, carbohydrate antigen (CA) 19-9, CA 72-4, alpha-fetoprotein, or immunosuppressive acidic protein. However, there was a significant relationship between serum IL-12 levels and soluble IL-2 receptor levels (r = 0.53, P < 0.01). CONCLUSION: Serum IL-12 levels in patients with far-advanced gastric cancer were significantly lower than those in patients with less-advanced gastric cancer. This is because macrophages in patients with far-advanced cancer would be hectic and unable to produce sufficient IL-12.

Leptin corrects increased gene expression of renal 25-hydroxyvitamin D3-1 alpha-hydroxylase and -24-hydroxylase in leptin-deficient, ob/ob mice.

Leptin, the ob gene product secreted by adipocytes, controls overall energy balance. We investigated leptin effects on bone metabolism using male leptin-deficient obese (ob/ob) mice, which had lower bone mineral density (BMD) and shorter femurs than lean (?/+) controls. Serum concentrations of calcium, phosphate, tartrate-resistant acid phosphatase (a bone resorption marker) and alkaline phosphatase, and urinary calcium and phosphate excretion were significantly elevated in ob/ob mice, whereas urinary concentrations of deoxypyridinoline did not differed between ob/ob and control mice. Because ob/ob mice develop severe hypogonadism, testosterone was administered to these mice for 10 wk (5 mg/kg, sc, twice weekly); this did not affect femoral BMD. Control and ob/ob mice showed similar vitamin D-receptor densities in bone and kidney; the obese mice had marked increases in serum 1,25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)] and in mRNA expression and activities of renal 25-hydroxyvitamin D(3)-1 alpha-hydroxylase (CYP27B1) and -24-hydroxylase (CYP24) compared with control mice. Leptin administration to ob/ob mice (4 mg/kg body weight, ip, every 12 h for 2 d) greatly reduced mRNAs and activities of 1 alpha-hydroxylase and 24-hydroxylase. Elevated concentrations of serum calcium, phosphate, and 1,25-(OH)(2)D(3) were normalized by leptin treatment. Thus, leptin suppresses renal gene overexpression for 1 alpha-hydroxylase and 24-hydroxylase and corrects increased serum concentrations of calcium and phosphate in ob/ob mice. Therefore, low BMD in leptin-deficient mice appears to be related to stimulation of bone resorption by 1,25-(OH)(2)D(3).

Serum soluble interleukin-2 receptor as a predictor of lymph node metastasis in early gastric cancer.

BACKGROUND: In the present study, we investigated the clinical significance of serum soluble IL-2R as a predictor of lymph node metastasis in patients with early gastric cancer. PATIENTS AND METHODS: Seventy-four patients with early gastric cancer were enrolled in this study. Levels of serum soluble IL-2R were measured by an enzyme-linked immunosorbent assay. RESULT: Significant differences in serum soluble IL-2R between the control group and cases of T1 were not recognized. On the other hand, levels of serum soluble IL-2R in 74 patients with early gastric cancer (T1) were significantly lower than those of T2, T3, and T4 (p < 0.05). There were no significant differences in serum soluble IL-2R between cases of mucosal and submucosal invasion (379 +/- 42 vs. 382 +/- 35 U/ml). Six of 35 patients with submucosal invasion (17.1%) had lymph node metastasis, but none of the 39 patients with mucosal invasion. In the 6 cases showing lymph node metastasis, the macroscopic types were IIc + Ul(+) in 4, and IIc + IIa and IIc + IIb in 1, respectively. Histopathologically, there were 5 poorly and 1 moderately differentiated adenocarcinomas. In 6 cases with lymph node metastasis, serum soluble IL-2R levels were significantly higher than in those without lymph node metastasis (556.8 +/- 73 vs. 329 +/- 22 U/ml, respectively, mean +/- SEM, p < 0.05). Five of these 6 cases demonstrated statistically significantly increased levels of serum soluble IL-2R (sensitivity 83%, specificity 63%), suggesting serum soluble IL-2R as a predictor of lymph node metastasis in early gastric cancer (p < 0.05). CONCLUSION: According to these data, in patients of early gastric cancer with increased levels of serum soluble IL-2R, endoscopic mucosal resection or minimal invasive gastrectomy without dissection of regional lymph nodes should be avoided, since there is a high risk of lymph node metastasis.