Expression of tumor necrosis factor-alpha stimulated gene-6 mRNA in cultured human uterine cervical fibroblasts

BACKGROUND: Uterine cervical ripening process is an active biochemical process similar in part to inflammatory reaction. In this process, hyaluronan plays important roles including facilitation of tissue hydration, release of matrix metalloproteinases and migration of inflammatory cells. The activities of hyaluronan are mediated by the hyaluronan binding proteins, hyaladherins. In the present study, we investigated the mRNA expression of tumor necrosis factor-alpha stimulated gene-6 (TSG-6), a member of the hyaladherin family, in cultured human uterine fibroblasts and uterine cervical tissues. METHODS: We developed one-step RT-PCR method for the quantification of TSG-6 mRNA and quantified the expression of TSG-6 mRNA in cultured human uterine fibroblasts, treated with or not proinflammatory cytokines, and TSG-6 mRNA in uterine cervical tissues. RESULTS: We clarified that [1] TSG-6 mRNA was expressed constitutively in cultured human uterine cervical fibroblasts, [2] expression of TSG-6 mRNA was upregulated in a dose dependent manner by proinflammatory cytokines, such as IL-1beta and TNF-alpha, which were key mediators in the cervical ripening process, [3] expression of TSG-6 mRNA in uterine cervices during parturition was significantly (P < 0.05) higher than that in a non-pregnant state. CONCLUSIONS: Our results suggest that TSG-6 might participate in the cervical ripening process.     

Fournier's gangrene: report of 4 cases

Fournier's gangrene is an infective necrotizing fasciitis of the perineal, genital or perianal region. We treated four cases of Fournier's gangrene from July 2002 to April 2003. All patients were male, ranging in age from 73-92 years old (80.5 +/- 6.5). They were admitted to our hospital complaining of perineal pain, scrotal swelling and high fever. Immediately, we started systemic chemotherapy with broad-spectrum antibiotics, and performed surgical debridements for all patients. Three patients made a full recovery, but one patient died of sepsis. These cases are presented with some notes on the relevant literature.     

Involvement of 90K/Mac-2 binding protein in cancer metastases by increased cellular adhesiveness in lung cancer

90K/Mac-2 Binding Protein (M2BP) plays a role in regulation of immune responses and cell adhesive ability in patients with cancer and infectious diseases. We previously reported that M2BP was highly expressed in lung cancer and that immune responses to M2BP were increased in many patients with lung cancer. To determine the involvement of M2BP in metastatic processes of cancer progression, we examined the ability of M2BP DNA-transduced lung carcinoma cell lines to adhere to extracellular matrices. Although expressions of cell-surface integrins were not modulated in the M2BP transfectants, they showed increased adhesiveness to fibronectin and collagen IV. We next analyzed the serum levels of M2BP in patients with lung cancer and normal donors and the relationships between M2BP expression and clinicopathological factors in the patients. The M2BP level was markedly elevated in the patients and was strongly correlated with nodal involvement and clinical staging. To determine whether expression of M2BP by cancer cells is modulated in the environment of tumor-bearing hosts, M2BP expression in M2BP-positive QG56 cells following exposure of the cells to pro-inflammatory cytokines was examined. The M2BP expression in QG56 cells was up-regulated by many of the cytokines that activate host protective immunity. The findings in this study suggest that M2BP plays a role in cancer metastasis by increased adhesiveness of cancer cells and that M2BP is increasingly produced even in a state of exposure to the host immune system. This molecule may be useful as a predictive factor of disease progression in lung cancer.     

Effect of bone-like layer growth from culture medium on adherence of osteoblast-like cells

The electrical polarization of ceramic HAp had an effect on the acceleration of bone restoration. Cell behavior in the bone-like growth layer was investigated. The deposits on the ceramic HAp was grown and formed layers by soaking in alpha-minimum essential medium supplemented with 10% fetal bovine serum (alpha-MEM supplemented with 10% FBS). The shapes of the adhering cells on the grown layer gradually changed from spindle to flat with growth of the layer. On the totally grown layer that was grown on the ceramic HAp by soaking in alpha-MEM supplemented with 10% FBS for 7 days, all the adhering cells were flat and the surface was filled with the grown cells. From these results, it was revealed that the grown layer on the ceramic HAp is one of the activation factors of cell growth. Consequently, cell growth was reinforced by acceleration of the layer growth on the negatively charged surface of the polarized ceramic HAp.     

Co-expression of CD44v3 and heparanase is correlated with metastasis of human colon cancer

Heparanase is an enzyme that degrades extracellular glycoprotein to release heparan sulfate molecules. CD44 variant exon 3 (CD44v3), a receptor for heparan sulfate, generates intracellular signals for cell migration. Production of CD44v3 and expression of heparanase were detected by immunohistochemistry and in situ hybridization, respectively. In 145 cases of colon cancer, heparanase mRNA and CD44v3 protein were detected in 46% and 43%, respectively. Co-expression of heparanase and CD44v3 was found in cases of 12% of Dukes' B, 32% of Dukes' C, and 57% of Dukes' D cases. Survival analysis found a significantly poorer prognosis in patients showing concurrent expression of heparanase and CD44v3 than in patients not showing both (p<0.0001). Concurrent expression of heparanase and CD44v3 might be a mechanism of cancer invasion and metastasis in colon cancer.     

Testicular malignant lymphoma: a case report

We report a case of malignant lymphoma arising from the testicle in a patient who had been on chemotherapy for a long period after orchiectomy. A 54-year-old male presented with indolent swelling in the right scrotum. Diagnosed as having a testicular tumor by ultrasonography and MRI, he underwent orchiectomy. According to the histopathological diagnosis, the tumor was classified as non-Hodgkin's lymphoma, diffuse large cell type, B cell type. Diagnosis of Stage I eA was made by the Arr Arbor classification. Four courses of cycrophosphamide, adriamycin, vincristin and prednisolone (CHOP) therapy were administered. COP (CHOP minus adriamycin) therapy has been given every four months on an out-patient basis. At present, 28 months after the operation, no evident recurrence has been found.     

MEK kinase 1 mediates the antiapoptotic effect of the Bcr-Abl oncogene through NF-kappaB activation

Bcr-Abl tyrosine kinase, a chimeric oncoprotein responsible for chronic myelogenous leukemia, constitutively activates several signal transduction pathways that stimulate cell proliferation and prevent apoptosis in hematopoietic cells. The antiapoptotic function of Bcr-Abl is necessary for hematopoietic transformation, and also contributes to leukemogenesis. Herein, we show for the first time that cell transformation induced by Bcr-Abl leads to increased expression and kinase activity of MEK kinase 1 (MEKK1), which acts upstream of the c-Jun N-terminal kinase (JNK), extracellular signal regulated kinase (ERK) and NF-kappaB signaling pathways. Inhibition of MEKK1 activity using a dominant-negative MEKK1 mutant (MEKK1km) diminished the ability of Bcr-Abl to protect cells from genotoxin-induced apoptosis, but had no effect on the proliferation of Bcr-Abl-transformed cells. Expression of MEKK1km also reduced NF-kappaB activation, and inhibited antiapoptotic c-IAP1 and c-IAP2 mRNA expression in response to the genotoxin. By contrast, neither JNK nor ERK activation was affected. These results indicate that MEKK1 is a downstream target of Bcr-Abl, and that the antiapoptotic effect of Bcr-Abl in chronic myelogenous leukemia cells is mediated via the MEKK1-NF-kappaB pathway.     

Prognostic significance of persistent mediastinal metastasis following induction therapy in large (&gt; or = 2cm) N2 or N3 non-small cell lung cancer

Objective: It is controversial whether or not surgery is beneficial for patients with non-small cell lung cancer accompanied by persistent lymph node metastasis in the mediastinum following induction therapy. We have therefore conducted a retrospective study to assess this issue Methods: Eligibility criteria were defined as follows: 1) the period of treatment was between January 1991 and April 1998, 2) the clinical stages were IIIA (N2) or IIIB (N3) with large lymph nodes (> or = 2 cm), 3) induction therapy had been administered, 4) tumor was resected completely, 5) at least one mediastinal lymph node had necrosis or scar if the pathological N status was p-N0 or p-N1 and 6) the p-stage was not IV. Dichotomous variables included the radiographic response of the tumor, the T status, and the N status. Results: Thirty-nine patients were eligible. There were 29 males and 10 females aged from 27 to 74 years, and involved 20 cases of adenocarcinoma. The pathological N status was as follows: p-N0 in 18 patients, p-N1 in 3, p-N2 in 16, and p-N3 in the other 2. In overall survival, the median survival time (MST) was 34 months and the actuarial 5-year-survival rate (5-YSR) was 28%. The group of patients with either N0 or N1 (n-21) had a 71-month MST and a 54% 5-YSR, and the group of patients with either N2 or N3 (n=18) had a 13-month MST and a 5-YSR of 0% (p<0.0001). On multivariate analysis, the pathological N factor was confirmed as an independently significant. Conclusions: Our retrospective study found that the survival rate of patients with persistent mediastinal nodal metastasis was very poor. A prospective study is needed to investigate whether or not surgery is beneficial for these patients.     

Supplementation of l‐arginine boosts the therapeutic efficacy of anticancer chemoimmunotherapy

Myeloid‐derived suppressor cells (MDSCs) play a crucial role in immunosuppression in tumor‐bearing hosts. MDSCs express arginase‐I and indoleamine 2,3‐dioxygenase; they suppress T‐cell function by reducing the levels of l ‐arginine and l ‐tryptophan, respectively. We examined the anticancer effects of supplementation of these amino acids in CT26 colon carcinoma‐bearing mice. Oral supplementation of l ‐arginine or l ‐tryptophan (30 mg/mouse) did not affect tumor growth, whereas oral supplementation of d ‐arginine was lethal. Supplementation of l ‐arginine showed a tendency to augment the efficacy of cyclophosphamide (CP). CP reduced the proportions of granulocytic MDSCs and increased the proportions of monocytic MDSCs in the spleen and tumor tissues of CT26‐bearing mice. l ‐Arginine supplementation alone did not affect the MDSC subsets. CP treatment tended to reduce the plasma levels of l ‐arginine in CT26‐bearing mice and significantly increased the number of tumor‐infiltrating CD8⁺ T cells. In addition, l ‐arginine supplementation significantly increased the proportions of tumor peptide‐specific CD8⁺ T cells in draining lymph nodes. Importantly, additional supplementation of l ‐arginine significantly increased the number of cured mice that were treated with CP and anti‐PD‐1 antibody. Totally, l ‐arginine supplementation shows promise for boosting the therapeutic efficacy of chemoimmunotherapy.