Evaluation of a combination chemotherapy with docetaxel and nedaplatin for patients with oral squamous cell carcinomas

The purpose of this study was to evaluate the effectiveness and safety of combination chemotherapy with docetaxel (TXT) and nedaplatin (CDGP) for patients with oral squamous cell carcinomas. Eight patients were enrolled in this study (4 men and 4 women, with a mean age of 61.7 years). TXT and CDGP were administered at a dose of 60 mg/m(2) and 70 mg/m(2) by drip infusion for 120 minutes, respectively. Three patients received one more administration 4 weeks after the first one. The locoregional response was evaluated 4 weeks after the final administration of TXT and CDGP. As a result, the locoregional response rate after 1 course was 62.5% including 25.0% of complete response (CR). The response rate after 2 courses was 100.0% with 66.7% of CR. According to Oboshi and Shimosato's classification, histological evaluation of surgical specimens revealed that four cases were Grade IIa, two cases Grade IIb, and two cases Grade IV. The severe adverse events were neutropenia and leukopenia, which were effectively managed with granulocyte colony-stimulating factor (G-CSF). No other severe side effects were recognized. The present study suggested that the combination chemotherapy with TXT and CDGP would be an effective and safe regimen in neo-adjuvant chemotherapy for oral squamous cell carcinomas.     

Tumor suppressive role of a 2.4 Mb 9q33-q34 critical region and DEC1 in esophageal squamous cell carcinoma

The key genes involved in the development of esophageal squamous cell carcinoma (ESCC) remain to be elucidated. Previous studies indicate extensive genomic alterations occur on chromosome 9 in ESCC. Using a monochromosome transfer approach, this study provides functional evidence and narrows down the critical region (CR) responsible for chromosome 9 tumor suppressing activity to a 2.4 Mb region mapping to 9q33-q34 between markers D9S1798 and D9S61. Interestingly, a high prevalence of allelic loss in this CR is also observed in primary ESCC tumors by microsatellite typing. Allelic loss is found in 30/34 (88%) tumors and the loss of heterozygosity (LOH) frequency ranges from 67 to 86%. Absent to low expression of a 9q32 candidate tumor suppressor gene (TSG), DEC1 (deleted in esophageal cancer 1), is detected in four Asian ESCC cell lines. Stably expressing DEC1 transfectants provide functional evidence for inhibition of tumor growth in nude mice and DEC1 expression is decreased in tumor segregants arising after long-term selection in vivo. There is 74% LOH in the DEC1 region of ESCC primary tumors. This study provides the first functional evidence for the presence of critical tumor suppressive regions on 9q33-q34. DEC1 is a candidate TSG that may be involved in ESCC development.     

Immunological evaluation of personalized peptide vaccination for patients with pancreatic cancer

The prognosis of pancreatic cancer is extremely poor, and development of new treatment modalities is needed. One such treatment could be specific immunotherapy. To evaluate safety and immunological responses, we conducted a phase I study of personalized peptide vaccination for pancreatic cancer patients (n=11). Namely, pre-vaccination peripheral blood mononuclear cells were screened for their reactivity in vitro to each of 14 or 16 peptides in HLA-A24(+) or -A2(+) patients, and only the reactive peptides (maximum: 4) were vaccinated in vivo. This regimen was generally well tolerated, although inflammatory reactions at the injection site were observed in 7 patients. Delayed-type hypersensitivity to peptides used for vaccination was observed in 7 patients. Increased cellular and humoral immune responses to at least one of peptides used for vaccination were observed in the post-vaccination PBMCs and sera from 4 of 8 patients and 4 of 10 patients tested, respectively. The 6- and 12-month survival rates for patients who received >3 vaccinations (n=10) were 80% and 20%, respectively. Due to tolerability and capability of inducing specific immunity, further development of personalized peptide-based immunotherapy for pancreatic cancer patients is warranted.     

Advanced chemoresistant breast cancer responding to multidisciplinary treatment with hyperthermia, radiotherapy, and intraarterial infusion

We employed multidisciplinary therapy, consisting of hyperthermia, radiotherapy, and intraarterial infusion, for a patient with progressive advanced breast cancer that was resistant to epirubicin hydrochloride and cyclophosphamide (EC) therapy as well as being resistant to docetaxel hydrate, and obtained a good therapeutic response. Because estrogen and progesterone receptors were both negative and HER2 was 3(+), administration of trastuzumab was started, and this patient has shown no signs of recurrence at 33 months after our treatment. The results suggested that our multidisciplinary therapy can be an effective method for the treatment of progressive breast cancer showing resistance to major chemotherapy agents such as anthracyclines and taxanes.     

Regulation of inducible nitric oxide synthase expression in advanced glycation end product-stimulated raw 264.7 cells: the role of heme oxygenase-1 and endogenous nitric oxide

Advanced glycation end products (AGEs) are closely linked to the development of diabetic atherosclerosis. The current study examines the induction of inducible nitric oxide (NO) synthase (iNOS) and heme oxygenase (HO)-1 expression by AGEs, as well as the signaling pathways involved and the interplay between these two enzymes. The stimulation of RAW 264.7 cells with 6.64 or 33.2 microg/ml AGEs leads to HO-1 protein expression, iNOS protein expression, and nitrite accumulation. AGEs lead to the phosphorylation of p42/44 and p38 mitogen-activated protein kinase (MAPK). The inhibition of p42/44 MAPK and protein kinase C prevented, whereas inhibition of p38 MAPK augmented, AGE-induced nitrite release and iNOS expression. In contrast, HO-1 expression was downregulated by inhibition of p38 MAPK. Furthermore, the expression of both proteins was prevented by coincubation with acetovanillone (NADPH oxidase inhibitor). AGE-induced iNOS expression was negatively regulated by stimulation of HO-1 expression with cadmium chloride or endogenous NO. Tin-protoporphyrin IX (HO-1 inhibitor) partially reversed the cadmium chloride-mediated downregulation of iNOS expression. The current study demonstrates that multiple signaling molecules are involved in AGE-stimulated iNOS and HO-1 expression. There also exists a downregulation of iNOS by its own product as well as the products of HO-1.     

A Case of Graft Infection 10 Years After Ascending Aorta Replacement

A 52-year-old man was admitted with anemia and slight fever, which he had for the last 2 months. He had undergone replacement of the ascending aorta for acute aortic dissection 10 years previously. Echocardiography demonstrated a flailing thin structure in the anterior wall of the ascending aorta corresponding to the proximal portion of the prosthetic graft. This abnormal echocardiographic finding led us to repeat blood cultivation. We finally detected Enterococcus facium and Staphilococcus epidermidis in his blood sample. We diagnosed this as a graft infection and prepared for surgical re-replacement of the infected graft. While he was waiting for the operation, an infectious aneurysm of a tibialis posterior artery ruptured and an emergency operation was done. Replacement of the infected ascending aorta graft was done thereafter. In surgery, 2-cm-long vegetation was found. It stuck to the graft wall near the former hole used for air removal in the first surgery. The patient recovered fully and left our hospital after 3 months of postoperative antibiotics therapy. This rare case of aortic graft infection long after the original replacement surgery suggests the importance of thorough echocardiographic investigation of prosthetic graft infection as a possible cause of fever of unknown origin.     

Complete response in an elderly patient with advanced gastric cancer treated with TS-1

The patient was an 89-year-old woman whose complaints were anorexia and weight loss. As a result of various examinations, she was diagnosed with advanced gastric cancer, Borrmann 3. TS-1 was administered at 75 mg/day for two weeks followed by one-week discontinvation during hospitalization; This course was then repeated after discharge. Anorexia and weight loss improved after two weeks, and complete response (CR) was obtained after 10 months of treatment. No cancer cells were confirmed by endoscopic biopsy. During this period no severe toxicities occurred. This TS-1 administration schedule appears to be a feasible and effective therapy for elderly patients with advanced gastric cancer.     

Optimal lymphadenectomy for squamous cell carcinoma in the thoracic esophagus: comparing the short- and long-term outcome among the four types of lymphadenectomy

Abstract Controversy continues over the optimal extent of lymphadenectomy (regional versus three-field) for a potentially resectable squamous cell carcinoma in the thoracic esophagus. In the Consensus Conference of the International Society for Diseases of the Esophagus (ISDE), held in Munich in 1994, the types of lymphadenectomy were classified as standard, extended, total, or three-field lymphadenectomy. The objective of the present study was to determine the optimal procedure among these four types of lymphadenectomy. The mortality and morbidity rates, postoperative course, and survival rates were compared among 302 patients who underwent curative (R0) transthoracic esophagectomy with one of these four types of lymphadenectomy at Kurume University Hospital, Fukuoka, Japan, from 1986 to 1998. Three-field lymphadenectomy resulted in better survival than any other type of lymphadenectomy for patients with positive lymph node metastasis from a cancer in the upper or middle thoracic esophagus. A postoperative complication, such as recurrent laryngeal nerve paralysis, anastomotic leakage, and tracheal ischemic lesion, was significantly more common after three-field lymphadenectomy. However, the mortality rate was the same among the four procedures. Three-field lymphadenectomy was optimal for an upper or middle thoracic esophageal cancer with metastasis in the lymph node(s) based on improved long-term survival, whereas there was not a large difference in short-term and long-term outcomes after the four types of lymphadenectomy for a lower thoracic esophageal cancer. Electronic Publication     

Detection of chromosomal aneusomy by fluorescence in situ hybridization for patients with nipple discharge

BACKGROUND: Breast carcinoma and precancer are believed to start in the lining of the milk duct or lobule. Ductography and fiberoptic ductoscopy (FDS) are used to identify abnormal intraductal lesions, although it is difficult to distinguish malignant from benign cases. Therefore, we studied the clinical usefulness of fluorescence in situ hybridization (FISH) analysis of a numerical aberration of chromosomes (aneusomy) using ductal lavage from patients with nipple discharge. METHODS: We applied ductography and FDS to 90 women who had nipple discharge. Ductal lavages obtained from patients with positive ductography and/or FDS findings were subjected to cytology and FISH analysis using centromere probes for chromosomes 1, 11, and 17. Patients with samples that showed aneusomy in at least one of the three chromosomes were diagnosed as positive. RESULTS: Histologic evaluation revealed 54 benign lesions and six malignancies. The sensitivity, specificity, and diagnostic accuracy were 33.3%, 88.9%, and 83.3%, respectively, for cytology and 100%, 100%, and 100%, respectively, for FISH. CONCLUSION: The results demonstrated that FISH has a diagnostic accuracy comparable to cytology. This technique has 100% specificity is making a definitive diagnosis of malignancy in patients with indeterminate cytologic results, suggesting that FISH diagnosis can be a good adjunct to cytology.