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This study represents a retrospective comparison of video-assisted thoracic surgery (VATS) lobectomy with standard open lobectomy for non-small cell lung cancer (NSCLC). The endpoints of this study include surgical stress as measured by interleukin 6 concentration and patient survival. A retrospective review was performed of 240 consecutive patients with clinical stage IA or IB NSCLC who underwent either VATS lobectomy (n?=?67) or conventional open lobectomy (n?=?173). The amount of blood loss was significantly less in the VATS group (110±75 ml) as compared to 165±90 ml for the open lobectomy group ( P <0.05). A significantly lower incidence of postthoracotomy pain occurred in the VATS group (6.2±4.1 times/3days) than in the open lobectomy group (13.5±5.8 times/3 days, P <0.0001). The postoperative interleukin (IL)-6 serum concentration of was significantly lower in the VATS group (112±43 pg/ml) than that in the open lobectomy group (351±133 pg/ml, P <0.001). There was no statistically significant difference in survival between the VATS and open lobectomy groups. The median follow-up was 42 months in both groups. VATS lobectomy for NSCLC is a reasonable treatment option for selected patients with stage I NSCLC. [ABSTRACT FROM AUTHOR]

The proteinase-activated receptor-2 (PAR-2) is a G protein-coupled receptor that is cleaved and activated by trypsin and tryptase. PAR-2 was widely expressed in human pancreatic cancer cell lines and in malignant and nonmalignant human pancreatic tissues. The expression of PAR-2 was found to be higher in the tissues with infiltrative growth pattern than those with expansive growth pattern. Moreover, significantly higher expression of PAR-2 was observed in the tissues that were accompanied with severe fibrosis. Even in the same specimen, the intensity of immunoreactivity tended to be stronger in the part accompanied with severe fibrosis than that accompanied with mild fibrosis. Similarly, the higher expression of PAR-2 was observed in chronic pancreatitis with severe fibrosis than with mild fibrosis. Higher expression of PAR-2 in pancreatic cancer showing infiltrative growth and higher degree of fibrosis may indicate that the activation of PAR-2 is involved in cancer invasion and the induction of fibrosis in human pancreatic cancer. [Copyright &y& Elsevier]

It has been reported that a large number of carcinoma cells are able to produce a variety of cytokines. We also reported that many carcinoma cell lines constitutively produce IL-8 in supernatant cultures. To evaluate the in vivo function of IL-8 of carcinoma cells, we investigated the expression of IL-8 and IL-8 receptors (IL-8R) in human carcinoma cells and the role of IL-8 and IL-8R in the growth of carcinoma cells. IL-8 mRNA was detected in 16 out of 20 (80%) carcinoma cell lines and 20 out of 24 (83.3%) carcinoma tissues by Northern blot analysis. IL-8R mRNA was expressed in 7 out of 11 (63.6%) carcinoma cell lines by reverse transcriptase–polymerase chain reaction (RT-PCR). Neutrophil chemotactic activity in supernatant cultures of carcinoma cell lines correlated with immunoreactive IL-8 concentration. Growth of carcinoma cells was significantly inhibited in the presence of anti-IL-8 antibodies or IL-8R antisense oligonucleotides. These results revealed that IL-8 and IL-8R are expressed in the majority of carcinoma cells, and it suggests that they might play a role in the growth of carcinoma cells.On the other hand, the NF-κB/Rel families are crucial transcriptional factors for regulation of IL-8 in immune and inflammatory responses. To determine if IL-8 production in carcinoma cells is associated with activation of nuclear factor κB (NF-κB), we investigated MCF-7 breast carcinoma cells with 12-O-teradecanoyl-phorbol-13-acetate (TPA) treatment. After TPA treatment, ELISA showed IL-8 production was increasing in culture supernatant. Western blotting revealed that in concert with the decline in cytosolic IκB, NF-κB exhibited similar kinetics of translocation to the nucleus. Electrophoric mobility shift assay (EMSA) also revealed that activation of NF-κB. These findings suggest that activation of NF-κB regulates IL-8 expression in carcinoma cells. [Copyright &y& Elsevier]

Similarities between cancer cells and neutrophil, such as circulating by single cells, attachment to the vascular system of the target and invasion into the target, lead to a hypothesis that cancer cells might produce neutrophil elastase or a very similar protease. Although the production of immunoreactive polymorphonuclear leukocyte elastase (ir-PMN-E) can be measured by enzyme immunoassay (EIA) in human cancer and cancer cell lines, we were having difficulty to detect this at mRNA level.TNF-α stimulation induces neutrophil elastase to a detectable level by RT-PCR in human cancer cell lines. In SUIT2, neutrophil elastase mRNA was detectable from 0.1 ng/ml of TNF-α stimulation which in EBC1 and MCF7 requires 1.0 ng/ml of TNF-α. For PC-3, there was no induction. The RT-PCR direct sequencing method revealed that the induced neutrophil elastase has no mutation.Although the amount of this molecule is low, as neutrophil elastase is a protease, the function in living systems does not depend on their amount but mainly on the activity they display. The result of this study indicates that some of the cancer cells could produce neutrophil elastase by stimulation of TNF-α and also suggests that neutrophil elastase produced by cancer cells is involved in clinical aspects of malignancy under inflammatory conditions. [Copyright &y& Elsevier]

Reverse transcription-polymerase chain reaction (RT-PCR) technique is extremely useful for sensitive detection of cancer cells, but it requires at least 8 h. If the precise information on the cancer spread based on RT-PCR is available during surgery, we can give the optimal therapy to each patient during operation. We aimed to establish the ultra-rapid procedure of RT-PCR for application to the intra-operative diagnosis. We have established a one-step real-time RT-PCR using LightCycler with hybridization probes, in combination with automated mRNA extraction on MagNA Pure LC. The method can be completed in only 70 min after sampling and has a comparable sensitivity to conventional RT-PCR and/or two-step real-time RT-PCR with a wide (10–106) dynamic range. When this method was applied to the intra-operative detection of free cancer cells in peritoneal lavage, the results were available during operation in all cases. We could detect cancer cells more effectively compared to conventional cytology and RT-PCR. This protocol is easily accomplished, delivers rapid, sensitive and reproducible results, and is therefore applicable to intra-operative diagnosis. [Copyright &y& Elsevier]

Purpose: We aimed to clarify the possibility of hematogenous spreading of cancer cells by microwave coagulation therapy (MCT) and radio-frequency ablation (RFA) for liver cancers. Molecular marker: Carcinoembryonic antigen (CEA) mRNA and melanoma antigen-3 (MAGE-3) mRNA were selected as a genetic marker. PCR method: Blood samples were collected before, during and just after the treatments. Genetic markers were examined using LightCycler reverse transcriptase–polymerase chain reaction (RT–PCR) assay with SYBR Green I. The samples with both positive markers were defined as genetic positive. Molecular metastasis and recurrence: We evaluated peripheral blood samples of 70 patients with liver tumors; 64 hepatocellular carcinomas (HCCs), 1 cholangiocellular carcinoma (CCC), and 5 metastatic liver tumors (MLTs). Genetic positive rates in RT–PCR assay before treatment were 42.2% in HCC, 0% in CCC, and 20% in MLT. Among genetic negative patients before operation, 45% of patients in MCT and 29% in RFA changed to genetic positive as a result of the procedures. Recurrence rates were 55% and 50% in MCT and 43% and 88% in RFA of the patients assessed negative to negative and negative to positive, respectively. Conclusion: Local ablation therapies may promote hematogenous seeding of cancer cells. [Copyright &y& Elsevier]

The established ultra-rapid quantitative RT-PCR system for intraoperative detection of intraperitoneal free cancer cells, the elucidated cause of peritoneal recurrence after curative operation for patients with non-serosa-invasive gastric cancer, and the extensive intraperitoneal lavage (EIPL) therapy for the prophylaxis of peritoneal recurrence from the results of evaluation using the ultra-rapid quantitative RT-PCR system were reviewed. We established ultra-rapid RT-PCR protocol that enables diagnosis of intraperitoneal cancer spread about 70 min, using LightCycler method in combination with automated mRNA extractor. Both the carcinoembryonic antigen (CEA) and cytokeratin (CK)20 messenger RNA (mRNA) in intraperitoneal lavages after lymph node dissection were identified in three (14.2%) and four (26.7%) patients with submucosal (SM) and muscularis propria (MP) tumors, respectively. Although peritoneal metastasis occurs in some patients with early gastric carcinoma, the reasons have not been fully established. These results clarified that peritoneal metastasis after operation for non-serosal-invasive gastric cancer was caused by opening lymphatic channels during lymph node dissection allowing the spread of viable cancer cells into the peritoneal cavity. Furthermore, EIPL method was performed in five cases with serosa-invasive (SE) gastric carcinoma, and its efficacy was evaluated by the quantitative RT-PCR. The quantitative RT-PCR demonstrated that EIPL reduced free cancer cells from 3.8×105±1.4×105 to 2.8±1.5 cells/100 ml of lavage by from six to eight washes, and they disappeared after the seventh to ninth wash. In conclusion, an ultra-rapid quantitative RT-PCR system for intraoperative detection of intraperitoneal free cancer cells was established for clinical use. It is suggested that the combination with the novel rapid detection system with the intraoperative therapy of EIPL can be a useful prophylactic strategy for peritoneal metastasis from gastric carcinoma. [Copyright &y& Elsevier]

In our previous studies, the cancer dissociation factor (DF), which can induce cell dissociation of weakly invasive pancreatic cancer cells (PC-1), was isolated from a highly invasive cell line (PC-10). In further study, mitogen-activated protein kinase 2 (MEK2) was discovered to be an invasion-metastasis related factor in this model. Extracellular signal-regulated kinase 2 (ERK2) is known to be the downstream kinase of MEK2 in the mitogen-activated protein kinase (MAPK) signaling pathway. Demonstration of the role of ERK2 in DF induced cell dissociation may contribute to elucidation of the signaling regulatory mechanism of tumor invasion-metastasis. The two cell lines mentioned above and the immunofluorescent method were used. In untreated cells, both total ERK2 and phosphorylated ERK (p-ERK) presented constitutively strong expressions in PC-1.0 cells, whereas the relevant expressions were quite weak in PC-1 cells. Nevertheless, addition of the conditioned medium containing DF to the PC-1 cells, significantly induced total ERK2 and p-ERK expressions and dissociation of islandlike cell colonies. Furthermore, the total ERK2 and p-ERK expressions, either the induced expressions in PC-1 cells or constitutive expressions in PC-1.0 cells, were seriously suppressed after treatment with the MEK2 phosphorylation inhibitor, U0126. Correspondingly, obvious cell colonies formation was observed in these two cell lines. In conclusion, ERK2 activation is closely correlated with the DF induced cell dissociation in pancreatic cancer cells. [Copyright &y& Elsevier]