Expression of Akt and Mdm2 in human esophageal squamous cell carcinoma

The Akt-Mdm2 pathway plays an important role in carcinogenesis in a variety of malignant tumors. However, the Akt-Mdm2 pathway in esophageal squamous cell carcinoma (ESCC) has not been fully studied. We investigated the proteins and mRNA expression of Akt and Mdm2 to elucidate the roles of these proteins in ESCC. We also examined the effect of Akt knockdown on Mdm2 expression in ESCC cells. ESCC tissue samples were obtained from 23 individuals who underwent surgical resection with no preoperative treatment. Akt1-3 and Mdm2 gene and protein expression were analyzed. The effect of siRNA-mediated Akt knockdown on Mdm2 expression was also studied, using ESCC cell lines. Akt1 and Mdm2 immunoreactivity was detected in 77.8 and 66.7% of tumor specimen from ESCC patients, respectively. Akt1 and Mdm2 mRNA expressions were correlated and significantly elevated in tumor tissue (p < 0.0001 and p < 0.05, respectively). The siRNA-targeted reduction of each Akt isoform reduced Mdm2 protein expression. The overexpression of Akt1 and Mdm2 may be related to esophageal carcinogenesis. Furthermore, Akt expression regulates Mdm2 expression, which may in turn regulate the function of wild-type p53. These results may provide the basis for future preventative or clinical therapies for esophageal cancer.     

Colorectal polypectomy and risk of colorectal cancer by subsite: the Fukuoka Colorectal Cancer study

BACKGROUND: Colorectal adenomas are well-established precursor lesions for colorectal cancer and removal of polyps is deemed to reduce the risk of colorectal cancer. However, benefit of colorectal polypectomy in routine practice is still uncertain. We therefore investigated subsite-specific risks of colorectal cancer in relation to history of colorectal polypectomy in a case-control study. METHODS: Both case patients and control subjects were residents aged 20-74 years in Fukuoka City and three adjacent areas. The case group comprised 840 patients undergoing surgery for a first diagnosis of colorectal cancer, while the control subjects were 833 residents who were selected in the community by two-stage random sampling. Past history of selected diseases, surgery and lifestyle factors were ascertained by in-person interview. Statistical adjustment was made for sex, 5-year age class, residence, smoking, alcohol drinking, physical activity, body mass index and parental history of colorectal cancer. RESULTS: Overall, 74 case patients (9%) and 85 control subjects (10%) reported a prior history of colorectal polyps, and 50 cases (6%) and 64 controls (8%) had a history of colorectal polypectomy. The adjusted odds ratio associated with colorectal polypectomy was 0.71 (95% confidence interval [CI] 0.48-1.06) for the overall risk of colorectal cancer. The corresponding values for cancer of the proximal colon, distal colon, and rectum were 1.68 (95% CI 0.98-2.88), 0.71 (95% CI 0.41-1.26) and 0.24 (95% CI 0.11-0.52), respectively. CONCLUSIONS: The findings indicate that colorectal polypectomy in current practice confers a decreased risk of rectal cancer and possibly of distal colon cancer.     

A case of advanced gastric cancer responding remarkably to neo-adjuvant combination chemotherapy using CPT-11 plus S-1

Adjuvant chemotherapy for advanced gastric cancer has not yet been established. We report a patient with advanced gastric cancer responding remarkably to neo-adjuvant combination chemotherapy consisting of CPT-11 and S-1. The patient was a 69-year-old woman diagnosed with large type 3 advanced gastric cancer with esophageal invasion and having No.3 lymph node metastasis (cT3, cN1, cM0, cStage IIIA), treated with 2 courses of CPT-11 plus S-1 as neo-adjuvant chemotherapy. Computed tomography after neo-adjuvant chemotherapy showed improvement of gastric wall thickness and reduction of lymph node metastasis. Subsequently, she underwent an operation. There was no lymph node swelling,so we performed curative surgery consisting of total gastrectomy, splenectomy, cholecystectomy, and D 2 lymph node dissection. Histological diagnosis was pT2 (MP), pN1, pStage II, and estimation of the histological change by chemotherapy was Grade 2. The course after surgery was good, and she was treated by S-1 after discharge. To date, 8 months after surgery, there is no evidence of recurrence. Combination chemotherapy consisting of CPT-11 plus S-1 can be performed safely as a neo-adjuvant treatment, and may be an effective treatment modality for advanced gastric cancer.     

Inflammatory mediators in diabetic and non-diabetic lumbosacral radiculoplexus neuropathy

Nerve microvasculitis and ischemic injury appear to be the primary and important pathogenic alterations in lumbosacral radiculoplexus neuropathy of patients with (DLRPN) and without (LRPN) diabetes mellitus (DM). Here, we examine the involvement of inflammatory mediators in DLRPN and LRPN. Paraffin sections of sural nerves from 19 patients with DLRPN, 13 patients with LRPN, and 20 disease control patients were immunostained for intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and nuclear factor κB (NF-κB). The findings were correlated with histopathology. The pathologic and immunohistochemical alterations of DLRPN and LRPN nerves were indistinguishable. The nerves of both types of LRPN had a significantly greater number of ICAM-1 positive vessels than did the controls (P < 0.01). TNF-α expression was seen in Schwann cells and some macrophages of DLRPN and LRPN nerves, whereas IL-6 expression was minimal. There was greater NF-κB immunoreactivity in vessels and endoneurial cells of DLRPN and LRPN nerves than of the controls (P < 0.001). NF-κB expression correlated with the number of empty nerve strands (P < 0.01) and the frequency of axonal degeneration (P < 0.05), whereas TNF-α expression correlated inversely with the number of empty nerve strands of teased fibers (P < 0.05). Our findings suggest that up-regulation of inflammatory mediators target different cells at different disease stages and that these mediators may be sequentially involved in an immune-mediated inflammatory process that is shared by both DLRPN and LRPN. Up-regulated inflammatory mediators may be immunotherapeutic targets in these two conditions. Nobutoshi Kawamura was a Research Fellow in Phillip A. Low’s Peripheral Neuropathy Research Laboratory. Supported in part by grants obtained from the National Institute of Neurological Disease and Stroke (NS 36797) (NS 32352) (NS 22352) (NS 43364).     

Screening for prostate cancer using prostate-specific antigen testing in Japanese men on hemodialysis

Objectives The objectives of this study were to evaluate the usefulness of serum prostate-specific antigen (PSA) screening in detecting prostate cancer in Japanese men on hemodialysis, and to analyze features of prostate cancer detected in these patients. Materials and methods This study included 115 male hemodialysis patients aged >55 years who agreed to the measurement of serum PSA value (group A) and 7529 men aged >55 years participating in a PSA mass screening test in Kobe City (group B) between April 2005 and March 2006. Prostate biopsy was recommended in men with serum PSA > 4.0 ng/ml in both groups. Seventy-eight patients with normal renal function aged >55 years diagnosed as having prostate cancer during the same time period as groups A and B were also included as a comparison group (group C). Results There was no significant difference in the distribution of serum PSA values between groups A and B. Prostate biopsy was performed in 8 and 205 men in groups A and B, respectively, and prostate cancer was detected in 5 and 68 in groups A and B, respectively; that is, there was no significant difference in the rate of positive prostate biopsy between these two groups (group A, 62.5%; group B, 33.2%), while the cancer detection rate in group A (4.3%) was significantly greater than that in group B (0.90%). In addition, there was no evident metastasis in five patients on hemodialysis who were diagnosed as having prostate cancer, and their serum PSA, clinical T stage and biopsy Gleason score were similar to those in group C. However, the percent of positive biopsy cores in these five was significantly greater than that in group C. All five were treated by maximal androgen blockade therapy, and all are currently alive without emergence of hormone-refractory diseases. Conclusions These findings indicate that hemodialysis patients may have an increased risk of prostate cancer, and that prostate cancer detected in such patients tends to be relatively advanced. Therefore, it would be recommended for hemodialysis patients to undergo PSA testing to screen for prostate cancer.     

CNS changes in neuro-Behçet's disease: CT, MR, and SPECT findings

CNS changes in three cases of neuro-Behçet's disease were observed by computed tomography (CT), magnetic resonance (MR) and single photon emission computed tomography (SPECT). The present study illustrates the reversibility of lesions in the brain stem with MR, while CT failed to show any abnormal findings in the region of the disease. We conclude that MR is a quite useful method to detect lesions in the brain stem and to evaluate the effects of treatment in neuro-Behçet's disease. SPECT is also an important method for the evaluation of dementia recognized in neuro-Behçet's disease.     

Chronic Herpes Simplex Encephalitis with Somnambulism: CT, MR and SPECT Findings

Abstract: A 64-year-old male with herpes simplex encephalitis had shown somnambulism and memory disturbance for nine months before consciousness disturbance appeared. Brain CT, MR and SPECT revealed lesions in the right temporal lobe. The atypical clinical course of this patient, including chronkity and focal symptom, is discussed.     

A patient with paraneoplastic limbic encephalitis induced by breast cancer presenting with hypersomnia]

A 50-year-old woman developed gait disturbance and hypersomnia over a period of a month. General physical examination revealed axillary lymph node swelling. On neurological examinations she was fully orientated but hypersomnic; short term memory disturbance, horizontal gaze evoked nystagmus and ataxic gait were observed. Electroencephalography disclosed a tendency for easily decreasing vigilance with delta activities but normal dominant rhythm. Cerebrospinal fluid examinations showed increased protein amounts (109 mg/dl) without either pleocytosis or atypical cells. An echogram of the breasts revealed a tiny mass in the left side. Pathological studies on a biopsied lymph node and the mass in her left breast showed a mammillary duct carcinoma. Brain MRI was normal, and no anti-neuronal antibody was detected in sera by two dimensional immunoblotting using human brain crude antigens. She was diagnosed as having paraneoplastic limbic encephalitis (PLE) associated with breast cancer. Over 42 hours polysomnography showed long total sleep time (TST) with a high ratio of sleep stage 1/TST and no REM sleep abnormalities; this resembled a thalamic-hypothalamic damaged sleep pattern. At first she was treated with plasma exchanges, but no improvement was observed. Hormonal and chemotherapies produced partial resolution of her neurologic symptoms and there were signs of reduction of the breast mass. Most reported PLE cases with hypersomnia have been associated with testicular cancer and anti-Ma antibodies. The present case is an extremely rare example manifesting hypersomnia without either testicular cancer or anti-Ma antibody. Since anti-tumor therapy successfully ameliorated her neurologic symptoms, cell-mediated immunity against a common tumor and neuronal antigens rather than hormonal immunity may have played a role in the development of her PLE.     

Effects of the oral or intratumoral administration of OK432 on the immuno-reactivities of regional lymph nodes in gastric cancer patients

The effects of OK432, a streptococcal preparation, administered either orally (PO-OK432) or intratumorally (IT-OK432) on the immuno-reactivities of regional lymph nodes were investigated in gastric cancer patients. Although native lymph node lymphocytes (LNL) from untreated patients did not show any cytotoxicities against K562 and Raji cells, enhanced activities were found in LNL from patients administered OK432. Augmenting effects on the cytotoxicities of LNL byin vitro additional OK432, interleukin 2 or γ-interferon were remarkable in the patients given IT-OK432. Moreover, the cytotoxicities of peripheral blood lymphocytes were augmentedin vitro more strongly in patients given IT-OK432 than in those given PO-OK432. Flow cytometric analysis of LNL revealed a decrease in CD4⁺ cells by PO-OK432 and an increase in CD8⁺ cells by IT-OK432. An increase in CD4⁺2H4⁺ cells and a decrease in CD4⁺2H4⁻ cells were observed in the patients given OK432, though CD8⁺CD11⁺ cells decreased by PO-OK432 while CD8⁺CD11⁺ cells increased by IT-OK432. Thus, it is suggested that LNL reactive to OK432 immunotherapy may differ between PO- and IT-OK432, and that the immunoreactivities of local lymph nodes and systemical immuno-reactivities may be highly potentiated by IT-OK432 rather than PO-OK432.