The TP53 pathway is frequently inactivated in human cancers. PICT1 (also known as GLTSCR2) is a novel regulator of the MDM2-TP53 pathway via its interaction with the ribosomal protein RPL11 in the ...nucleolus. However, the clinical significance of PICT1 in gastric cancer remains unknown.
To evaluate PICT1 function, we used shRNA to inhibit PICT1 expression in gastric cancer cells that expressed wild-type TP53. PICT1 expression and TP53 mutation status were quantified in 110 cases of primary gastric cancer to explore the impact of PICT1 expression levels on gastric cancer.
Deficiency of PICT1 significantly impaired cell proliferation and colony formation via TP53-mediated cell cycle arrest. Following induction of PICT1 deficiency, RPL11 translocated out of the nucleolus. Of the 110 gastric cancer samples tested, 70 (63.6%) and 40 (36.4%) tumours expressed wild-type and mutant TP53, respectively. In gastric cancer patients with wild-type TP53 tumours, patients with relatively low PICT1 expression levels had a better prognosis compared with high expression level patients (P=0.046).
The findings suggest that PICT1 has a crucial role in gastric cancer progression by regulating the MDM2-TP53 pathway through RPL11. Clinically, PICT1 expression is a novel prognostic parameter in gastric cancer patients with wild-type TP53 tumours.
Background The therapeutic potential of using stem cells is tremendous. Mesenchymal stromal cells (MSC) have now been isolated in various tissues including bone marrow (BM), muscle, skin and adipose ...tissue. Among them, adipose tissue could be one of the most suitable cell sources for cell therapy, because of its easy accessibility, minimal morbidity and abundance of stem cells. The large numbers of stem cells in adipose tissue means that clinically relevant stem cell numbers could be extracted from the tissue, potentially eliminating the need for in vitro expansion. To utilize these characteristics of adipose tissue fully, Cytori Therapeutics Inc. has developed a closed system called Celution™ to isolate and concentrate stem cells and regenerative cells automatically from adipose tissue. Methods Adipose tissue-derived cells were isolated using the Celution™ system. The output from the Celution™ was characterized using multicolor FACS analysis with CD31, CD34, CD45, CD90, CD105 and CD146. The multidifferentiation potential of the cells was analyzed using adipogenic and osteogenic media. Results Our results showed that cells from the Celution™ are composed of heterogeneous cell populations including adipose-derived stem cells (ASC) (CD31− CD34+ CD45− CD90+ CD105− CD146− ), endothelial (progenitor) cells (CD31+ CD34+ CD45− CD90+ CD105− CD146+ ) and vascular smooth muscle cells (CD31− CD34+ CD45− CD90+ CD105− CD146+ ). We also confirmed the output contains cells able to differentiate into adipogenic and osteogenic phenotypes. Our results show that cells isolated with the Celution™ and manually are equivalent. Discussion Cells from adipose tissue can be processed by Celution™ within the time frame of a single surgical procedure. This system could provide a ‘real-time’ treatment setting that is cost-effective and safe.
Vascular endothelial growth factor-C (VEGF-C) functions specifically to induce lymphangiogenesis. We examined the relationship between expression of VEGF-C and clinicopathological features in ...patients with colorectal cancer. The expression of VEGF-C in the 99 primary tumours and 18 metastatic lymph nodes from colorectal cancer patients was examined immunohistochemically. To verify VEGF-C mRNA expression, reverse transcriptase-polymerase chain reaction (RT-PCR) was carried out. The expression of VEGF-C correlated with lymphatic involvement, lymph nodes metastasis, and depth of invasion. On the other hand, correlations were nil with regard to gender of the patients, histologic type, venous involvement, and liver metastasis. The expression of VEGF-C in metastatic lymph nodes was fairly consistent with this expression in the primary tumour. Survival time was shorter for VEGF-C positive groups than for VEGF-C negative ones, but with no statistically significant difference. RT-PCR findings revealed that the expression of VEGF-C mRNA correlated mostly with that of VEGF-C protein expression. VEGF-C may play an important role in lymphatic spread of colorectal cancer.
Aim: Angiopoietin 1 (Ang-1) and its antagonist, angiopoietin 2 (Ang-2), are novel ligands that regulate the Tie2 receptor. The Ang-2 gene is upregulated in the hypervascular type of human ...hepatocellular carcinoma (HCC). To gain a better understanding of the role of the Ang–Tie2 system in HCC the expression of these genes was investigated in a series of human HCCs. Methods: The expression of the angiopoietin and Tie2 proteins was investigated in nine normal liver tissues and 52 surgically resected HCCs. In addition, the effects of hypoxic stimuli on Ang-1, Ang-2, vascular endothelial growth factor (VEGF), and erythropoietin (EPO) expression was investigated in Hep3B cells. Results: Ang-1, rather than Ang-2, was more frequently expressed in the normal liver. Ang-1 was expressed in 68% of HCCs, whereas Ang-2 was expressed in 81%, and was significantly higher in poorly differentiated HCCs characterised by high vascularity (p = 0.02), and in tumours with a peliotic change (p = 0.02). Strong expression of Tie2 was seen in tumour vessels in accordance with Ang-2 expression. In Hep3B cells, hypoxic stimuli upregulated VEGF and EPO, but not Ang-1 or Ang-2. Conclusions: These data support the evidence that the reversal of Ang-1 and Ang-2 expression plays an important role in the angiogenic and dedifferentiation processes in HCC. The hypoxic stimuli were not responsible for Ang-2 upregulation, unlike that of VEGF, in human HCC cells.
A recent study disclosed that breast cancer cases with low 'tau' expression can predict susceptibility to Paclitaxel administration. In the current study, the clinical significance of tau expression ...in gastric cancer cases was established by identifying candidates with Paclitaxel administration. Tissue specimens from 20 cases of in-operable or noncuratively resected gastric cancer were examined. Subsequent to the administration of 80 mg m(-2) of Paclitaxel in six 3-h intravenous infusions, the clinical effectiveness of Paclitaxel was evaluated by the size of metastatic lesions with computed tomography. The status of the tau expression was determined by immunohistochemistry. Based on a previously reported classification scheme, six were classified as tau-negative expression (0, 1+) cases and 14 were classified as tau-positive expression (2+, 3+) cases. All six (100%) cases of tau-negative expression showed a favourable response (partial response or minor response) to Paclitaxel administration. However, 12 (86%) of the 14 cases of tau-positive expression showed progressive disease (n = 11) or no change (n = 1) after Paclitaxel administration. The serum carcinoembryonic antigen values of the six cases of tau-negative expression were markedly decreased in comparison to the 14 tau-positive cases. These data indicate that tau-negative expression can be used to select gastric cancer patients, which will favourably respond to Paclitaxel treatment.
E-cadherin, a calcium-dependent cell-cell adhesion molecule, plays a key role in the maintenance of tissue integrity. The function of this molecule is partly mediated by alpha-/beta-/gamma-catenin. ...Loss or dysfunction of E-cadherin is associated with an invasive phenotype. We analyzed the expression of E-cadherin and beta-catenin in human lung cancer to determine the relationship to clinicopathological factors and prognosis. E-cadherin and beta-catenin expressions were evaluated in 331 lung cancer tissues in a immunohistochemical analysis. Reduced E-cadherin expression was evident in 138 (42%), and reduced beta-catenin expression was noted in 122 (37%). Reduced E-cadherin expression significantly correlated with lymph nodes metastasis (P = 0.0199). E-cadherin expression significantly correlated with increasing histological differentiation (P = 0.0403). Although reduced E-cadherin did not correlate with the prognosis (P = 0.0652), reduced beta-catenin expression did significantly correlate with a poor prognosis (P = 0.0001). When both were reduced, there was a significant unfavorable prognosis compared with either the reduced expression (P = 0.0493) and preserved expression (P = 0.0003). Multivariate analysis showed a significantly lower survival rate for patients with reduced beta-catenin (P < 0.0001). We interpret these data to mean that dysfunction of the cell-cell adhesion molecule has a role in the progression of lung cancer and that analysis of E-cadherin and beta-catenin expression can provide clinically important evidence on which to base treatment.
This study set out to evaluate, in patients with metastatic colorectal carcinoma, the efficacy and toxicity of S-1, which contains tegafur, 5-chloro-2,4-dihydroxypyridine (CDHP) and potassium ...oxonate, based on a biochemical modulation of 5-fluorouracil (5-FU) targeted at inhibition of dihydropyrimidine dehydrogenase (DPD). Sixty-three patients with measurable metastatic colorectal carcinoma were enrolled into the study. None of the patients had received prior chemotherapy except for adjuvant setting. S-1 was administered orally twice daily at a standard dose of 80 mg m(-2) day(-1) for 28 days followed by a 14-day rest. This agent is continued until disease progression, unaccepted toxicity, or patient refusal. Twenty-two (35%) of the 62 eligible patients achieved PR with a 95% confidence interval of 25-48%. Five of the 10 patients with a history of adjuvant chemotherapy achieved partial remission. The median survival time was 12 months. Major adverse reactions included myelosuppressive and gastrointestinal toxicities, though their incidence of grade 3 or 4 being 13% in neutropenia and less than 10% in the others. None of the 53 patients treated as outpatients required hospitalization due to adverse reactions: These results suggest that S-1 achieves similar responses to those of infusional 5-FU plus leucovorin and shows the potential of another biochemical modulation with easily manageable toxicity.
Aims: The relationship between the pre-operative nutritional condition and the outcome of the surgical treatment in patients with oesophageal carcinoma has been discussed diversely. The aim of the ...current study was to demonstrate the relationship between pre-operative nutritional condition and post-operative complications and prognosis following surgical treatment for oesophageal carcinoma.
Methods: Two hundred and fifty-eight patients with oesophageal carcinoma treated with oesophageal resection and reconstruction were selected. The correlation of pre-operative values of prognostic nutritional index (PNI) with the incidence of post-operative complications and prognosis of the patients was investigated.
Results: The mean pre-operative value of PNI in patients with post-operative complications (41.8±5.4) was significantly lower than that in patients without post-operative complications (46.5±5.3;P <0.0001). The survival in patients with higher PNI value was significantly more favourable than that in patients with lower PNI value (P=0.0001).
Conclusions: Pre-operative assessment of the nutritional condition could provide predictive information for post-operative complications in patients with oesophageal carcinoma.
With the growth and sophistication of laparoscopic surgery, increased attention is now being focused on safety and complications.
In an attempt to address questions regarding the safety of ...laparoscopic surgery, a retrospective study of the time period from January 1991 to December 1995 was conducted by the Study Group of Endoscopic Surgery in Kyushu, Japan.
The response rate was 84.4% (152 of 180 hospitals). During the last 5 years 17,626 patients underwent endoscopic operations and 87.5% (15, 422 patients) had laparoscopic surgery while 12.5% (2,204 patients) underwent thoracoscopic surgery. In 96.6% of the hospitals a minimal open laparotomy was used. Among the various operations, a cholecystectomy was performed in the largest number of patients (13, 787). The total number of complications was 415 (2.7%), of which 156 (37.6%) were related to needle or trocar insertion. Visceral injury was found in 22 patients (0.14%): major vessel injury in 10, gastrointestinal tract injury in 11, and liver injury in one patient. Abdominal wall injury was seen in 79 patients (0.52%), bleeding in 70 (0.46%), and a hernia in 9 (0.06%). Extraperitoneal insufflation occurred in 55 patients (0.36%). There was no mortality. The complication rate significantly decreased year by year after the use of laparoscopic surgery began.
The most common complications of laparoscopic surgery are related to needle and trocar insertion. These are preventable by placement under direct vision with verification of the intraperitoneal location of the needle and trocar.
To evaluate the impact of graft size on recipients in living donor liver transplantation (LDLT) to establish a clinical guideline for the minimum requirement.
Although the minimum graft size required ...for LDLT has been reported to be 30% to 40% of graft volume (GV)/standard liver volume (SLV), the safety limit of the graft size was unknown.
A total of 33 cases of LDLT, excluding auxiliary transplantation, were reviewed with a minimum observation period of 4 months. The 33 patients were divided into three groups according to GV/SLV: medium-size graft group, small-size graft group, and extra-small graft group. The effect of GV/SLV on graft function, graft regeneration, and survival was evaluated.
The overall patient survival rate was 94% at a mean follow-up of 15 months with a minimum observation period of 4 months. There were no statistically significant differences in postoperative bilirubin clearance, alanine aminotransferase, prothrombin time, and frequency of postoperative complications among the three groups. One week after transplantation, the regeneration rate (GV at 1 week/harvested GV) in the extra-small and small groups was significantly higher than that of the medium group. The graft and patient survival rates were both 100% in the extra-small group, 75% and 88% in the small group, and 90% and 95% in the medium group.
Small-for-size grafts less than 30% of SLV can be used with careful intraoperative and postoperative management until the grafts regenerate.