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Accumulation of chlorine e6 derivatives in cells with different level of expression and function activity of multidrug resistance protein P-gp 170.

AIM: This work deals with studying the influence of overexpression and function activity of multidrug transporter protein P-gp 170 on the intracellular accumulation of several porphyrin sensitizers, including chlorin e6 (Chl e6), di- (DME) and trimethyl esters (TME) of Chl e6. METHODS: A parental IM9 cell line and two IM9 drug-resistant IM9 sublines were used. With flow cytometry technique the rates of chlorines accumulation in different IM9 cells and values were related to the extent of multidrug resistance (MDR) phenotype. RESULTS: Using P-gp 170-specific antibodies and fluorescent probe JC-1 an increased expression and function activity of P-gp 170 was detected for drug-resistant cells. It was obtained that drug-resistant IM9 cells accumulated chlorines to a lesser extent than the respective wild type, however the differences did not exceed 30%. Verapamil, cyclosporine, known to reverse the MDR phenotype affects equally IM9-Vinc IM9-Tax and Im9 cells. CONCLUSION: Our results demonstrate that the P-gp 170 does not appear to play a role in the intracellular accumulation of chlorines. Since the enhanced activity of P-gp 170 in tumor cells is a factor of their resistance to the action of various antitumor drugs, we conclude that photodynamic therapy could be useful in killing cells exhibiting the MDR.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[125I seed implantation in sphincter preservation for treatment of low rectal cancer].

OBJECTIVE: To evaluate the effects of (125)I seed implantation in sphincter preservation for treatment of low rectal cancer. METHODS: Seventy-six patients with low rectal cancer were randomly divided into 2 group: group A, 17 males and 13 females, aged 48.5 +/- 2.4, receiving rectostomy and anal sphincter preservation and group B, 24 males and 22 females, aged 49.4 +/- 2.6, receiving modified TME and anal sphincter preservation combined with brachytherapy by (125)I seed implantation. Two to four weeks after operation chemotherapy with 5-FU/CF were performed. Follow-up was carried out 6, 12, 24, and 36 months after operation. RESULTS: The local recurrence rates 6, 12, 24, and 36 months after operation were 0%, 11.1%, 14.3%, and 23% respectively in the group A, and all 0% in the group B (P < 0.05 for the rate 36 months later). The survival rates 6, 12, 24, and 36 months after operation were 100%, 100%, 85.7%, and 76.7% respectively in the group A, and were 100%, 100%, 97.1%, and 93% respectively in the group B (P < 0.05 for the rate 36 months later). The functions of defecation and erection were better in the group B and the symptom of pain was improved better in the group A too (all P < 0.05). CONCLUSIONS: Safe, simple, and effective, surgery with sphincter preservation combined with brachytherapy in low rectal cancer is one of the ideal methods for treatment of low rectal cancer.

Adenocarcinoma↗

[Study with large slice technique and tissue microarray on lymph node involvement and micro-metastasis of rectal cancer].

OBJECTIVE: To study lymph node involvement and micro-metastasis of rectal cancer with large slice technique and tissue microarray. METHODS: Large slice technique, combined with tissue microarray,was used in pathologic study of 31 patients after total mesorectal excision (TME) for rectal cancer. RESULTS: Nine hundred and ninety- two lymph nodes were harvested and 148 were positive. More than 40% of positive lymph nodes were located in the outer layer of the mesorectum and in the same side of the mesorectum as the primary tumor was. Circumferential margin involvement was observed in 12 cases and correlated with the numbers of metastatic lymph nodes (Beta =1.166, P=0.041). Micrometastasis was found in 9 cases with negative pathological lymph nodes, but not correlated with tumor differentiation and stage (P> 0.05). CONCLUSION: Large slice technique combined with tissue microarray facilitates the detection of lymph node involvement and micrometastasis. There is a predominance of lymph node metastasis in the outer layer and the same side of the mesorectum. Micrometastasis can be discovered in different stages of rectal cancer.

Adult↗

[Spongiform encephalopathies with special reference to bovine spongiform encephalopathy].

In Switzerland bovine spongiform encephalopathy (BSE) was detected for the first time in November 1990. It is a transmissible disease of the central nervous system similar to Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker syndrome (GSS) and kuru in man, and, in animals, scrapie in sheep and goats, chronic wasting disease (CWD) in captive mule deer and elk of North America and transmissible mink encephalopathy (TME) of farm reared mink. The infectious agent of the spongiform encephalopathies (SEs) is extremely small (greater than 100 microns) and very resistant against physical and chemical disinfectants. The infectiousness is closely linked to the so-called prion proteins, the biological and genetic properties of which are not yet fully understood. The first outbreak of BSE occurred in England, and the disease spread rapidly all over Great Britain. The source of infection proved to be bone and meat meal obtained from scrapie-infected slaughter wastes. So far we have diagnosed 17 cases of BSE in our country. The risk of humans contracting CJD by ingestion of meat, milk and their products contaminated with BSE is probably minimal.

Animals↗

[Rectal cancer: locoregional recurrence in relation to surgical and complementary treatment].

Much recent data have been published on the risk of local recurrence (LR) following curative surgery for rectal cancer and the impact of adjuvant therapy. On the other hand, improvements in surgical techniques, as the total mesorectal excision, have apparently reduced the risk of LR. Furthermore, in selected cases, neoadjuvant therapy seems to reduce much more the incidence of LR. A list of prognostic factors which affect the onset of LR, other than the different procedures, was considered. To investigate such evidences a retrospective analysis was undertaken in our series, focusing on examination of the employed techniques as potential predictors of local recurrence. Thus, in a 18-yr-period (1986-2003), two hundred and ninety-five patients who had undergone elective curative surgical resection of rectal cancer were included in the study. The demographic, operative and follow-up data were collected retrospectively. All patients underwent total mesorectal excision, whereas neoadjuvant therapy was performed in a selected series of patients, according to defined entry criteria patterns. Results evidenced LR in 7.1% of patients and occurred between 6 months to 8 year following surgery. Comparisons were made between patients who had different surgical procedures; indeed sphyncter saving procedures correlated with a higher incidence of LR rather than abdomino-perineal resection. Pelvic recurrences were observed more frequently compared to the anastomotic ones. A limited number of patients with LR underwent surgery due to the associated condition of metastatic lesions; the follow-up related to such series evidenced a mortality rate of 57% within 3 year from reoperation. A low local recurrence rate can be achieved after total mesorectal excision (TME) without preoperative radiotherapy. Our results suggest that preoperative radiotherapy may be employed only for those patients who are at a higher risk for local recurrence.

Combined Modality Therapy↗

[Neoadjuvant radiochemotherapy of rectal carcinoma: retrospective analysis of a personal experience].

Even if surgical resection continues to be the mainstay of treatment in rectal cancer, preoperative chemoradiation may downstage locally advanced rectal cancer, in some cases with no residual tumors. Compared with surgery alone, preoperative radiotherapy and chemotherapy improves outcomes in patients with locally advanced rectal cancer. In the present review we summarize the results of preoperative chemoradiation therapy in a group of 15 patients who underwent surgical resection with total mesorectal excision (TME) for advanced mid and low rectal cancer from February 2002 to February 2004.

Aged↗

[Colorectal laparoscopic surgery. Single center experience with 599 cancer patients].

PURPOSE: To analyze the results of laparoscopic colectomy for cancer of colon and rectum on early outcome. METHODS: Fifty hundred and ninety-nine consecutive unselected patients who underwent laparoscopic colectomy for cancer of the colon or rectum between January 1998 and December 2004 in a single Institution were prospectively evaluated. Tumor classification was by TNM stage. Patients were monitored for postoperative complications for 30 days after surgery. Follow-up was done by direct patient contact. RESULTS: Mean (SD) age was 65.8 (11.7) years. Mean (SD) ASA score was 2.0 (0.5). The following operations were performed: 248 left colectomies, 131 right colectomies, 26 sigmoid resections, 164 rectal resections, 21 abdominoperineal resections (Miles operation) and 9 total colectomies. Conversion rate was 7.2% (43/599 pts). The overall morbidity rate was 23.3% (143/599 pts). The mortality rate was 0.3% (2/599 pts). Anastomotic leak occurred in 45/599 (7.3%) patients. Re-operation rate was 4.6% (26/599 pts). Mean (SD) length of stay was 9.9 (5.8) days. The mean number (SD) of lymphnodes intraoperatively collected was 16.7 (9.8). Median (range) time of follow-up period was 20.2 months (6-68). One port-site metastasis was found at 18 months after surgery. Overall 5-years survival was 81%. Local recurrence rate in patients who underwent TME of the rectum was 4.4%. CONCLUSION: Laparoscopic colectomies is safe and effective in the treatment of colon and rectal cancer.

Aged↗

[Efficacy of intersphincteric resection in the sphincter-preserving operation for ultra-lower rectal cancer].

OBJECTIVE: To evaluate the clinical efficacy of intersphincteric resection in the sphincter- preserving operation for ultra-lower rectum cancer. METHODS: Thirty-one rectal cancer patients with the distal edge of the tumour less than 2 cm from the dentate line were evaluated. Eighteen advanced rectal cancer patients received preoperative chemo-radiation. Total mesorectal excision (TME) was performed with the rectum immobilized down, and the puborectal ligament and partial levator cut to the level of the dentate line. In some well-exposed patients, it was possible to further immobilize the rectum between the external sphincter ring and the rectum inner sphincter wall. In anal approach,good exposure was attained and the cut-line was made vertically to the anal canal 2 cm below the lower edge of the tumor, and further intersphincteric immobilization was made upright. Colon or colon pouch were anastomosed to the distal anal wall. RESULTS: There was no peri-operative death. Thirty patients had good fecal control. Twenty-nine patients showed no evidence of recurrence or metastasis after follow-up for 12 months. Recurrence occurred in one case 1 year after operation. Another one had higher CEA 19.9 level, but without evidence of metastasis. CONCLUSION: Radical resection can be attained and anal sphincter preserved by intersphincter resection which is an alternative sphincter-preserving operation.

Anal Canal↗

[Analysis of recurrence and prognosis after surgical resection for I stage lower rectal carcinoma].

OBJECTIVE: To investigate the clinicopathologic factors related with recurrence and prognosis after surgical resection for I stage lower rectal carcinoma. METHODS: The related clinicopathologic factors for recurrence and prognosis of 166 patients with I stage lower rectal carcinoma after surgical resection were retrospectively analyzed using univariate and multivariate methods. RESULTS: A total of 138 patients with I stage lower rectal carcinoma received radical resection according to the operative rules of total mesorectal excision (TME). Ninety-three patients received abdominoperineal resection (APR) operation, 45 patients received sphincter preserving operation, and 28 patients received local excision. The local recurrence rates were 6.5% (6/93), 2.2% (1/45), 17.9% (5/28), respectively . Histological differentiation and operative procedures were associated with local recurrence. The 5-year survival rates were 91.1% in APR group, 95.5% in sphincter preservation group and 82.6% in local resection group. Univariate analysis revealed that histological differentiation and local recurrence were correlated with prognosis. Multivariate analysis revealed that local recurrence was the most important prognostic factor for I stage lower rectal carcinoma. CONCLUSIONS: Radical resection of I stage lower rectal carcinoma has low recurrence rate and better prognosis. Sphincter preserving operation and local excision must be strictly selected in proper patients.

Adult↗

Impaired anastomotic healing after preoperative radiotherapy followed by anterior resection for treatment of rectal carcinoma.

BACKGROUND: Patients with rectal carcinoma undergoing total mesorectal excision (TME) have a lower recurrence rate with preoperative radiotherapy (RT). The aim of this study was to assess the side-effects in patients who had preoperative RT compared with those who did not receive it (because of palliative resections, advanced age or refusal). METHODS: From January 2001 to March 2003, 40 patients underwent resection and double-stapled anastomosis for rectal carcinoma. We compared 17 patients who received RT followed by resection and low rectal anastomosis, with 23 patients who did not have RT. RESULTS: After surgery 7/17 of the patients who had received RT developed anastomotic leaks. Anastomotic leakage was seen only once in the patients who did not have RT (41% v. 4%, p = 0.006). A protective stoma, which was performed in 11 patients in the RT group, did not prevent anastomotic leakage (4/11 leakage with stoma v. 3/6 leakage without stoma, p = 0.64). Median hospital stay was longer in the RT group (17.4 v. 13.7 days, p = 0.017). There was no difference in the number of minor postoperative complications between the two groups (24% v. 22%). CONCLUSION: Compared with surgery alone, preoperative short-term RT increased the number of anastomotic leaks and hospital stay, whether or not a protective stoma was performed.

Adult↗

[Distribution of micrometastatic nodules of low rectal cancer in mesorectum: a pathological study using whole-mount sections].

OBJECTIVE: To investigate the regional spread of micrometastatic nodules in the mesorectum from low rectal cancer, and provide further pathological evidence to optimize radical resection procedure for rectal cancer. METHODS: A total of 62 patients with low rectal cancer underwent low anterior resection and total mesorectal excision (TME) was included in this study. Surgical specimens were sliced transversely and serial embedded blocks were made at 2.5 mm interval, and paraffin sections were stained with hematoxylin and eosin. The mesorectum on whole-mount sections was divided into three regions: outer region of mesorectum (ORM), middle region of mesorectum (MRM) and inner region of mesorectum (IRM). Microscopic spread were examined microscopically on the sections for the distribution in different mesorectal regions, frequency, types, involvement of lymphatic system and correlation with the primary tumor. RESULTS: Microscopic spread of the tumor in mesorectum and ORM was observed in 38.7% (24/62) and 25.8% (16/62) of the patients, respectively. Circumferential resection margin (CRM) involved by microscopic tumor foci occurred in 6.5% (4/62) of the patients, and distal mesorectum (DMR) involvement was recorded in 6.5% (4/62) with a spread extent within 3 cm of distal border of the main lesions. Most (20/24) of the patients with microscopic spread in mesorectum were in TNM stage III. CONCLUSION: Results of the present study support that complete excision of mesorectum without destruction of the ORM is essential for surgical management of low rectal cancer, and an optimal DMR clearance resection margin should not be less than 4 cm.

Adenocarcinoma↗

[Clinico-morphological study of transmissible encephalopathy of mink].

Histological examination of the central nervous system of naturally infected and dying minks revealed the picture of "status spongiosus" in the brains and spinal cords, lysis and loss of neurons, hypertrophy and proliferation of astroglia typical of transmissible mink encephalopathy (TME). The disease in minks was induced experimentally by oral, suboccipital, intramuscular, intraperitoneal, and subcutaneous routes of inoculation inducing typical clinical signs and histological lesions. Suspensions prepared from the infectious material obtained from the Institute of Poliomyelitis and Viral Encephalitides, Acad. Med. Sci. USSR. were used for inoculations. The incubation period varied from 7 to 9 months with different routes of inoculation. The infection could be reproduced by keeping the infected and normal animals together. Transmission of the disease from sick mothers to their offsprings was also observed. Electron microscopic studies revealed ultrastructural changes characteristic of transmissible encephalopathies.

Animals↗

Slow viral infections of animals: experimental models for human disease.

Sigurdsson's three criterions for a slow viral infection are quoted and discussed and the background of his work briefly described. A fourth criterion for a slow viral infection, is suggested, infection of the hosts lymphoid tissues, which is a common feature of slow infections that have been observed. The general properties of the maedi-visna virus, the diseases and the immune response it causes are discussed. Sheep and goats are susceptible to natural maedi-visna infection. In the goat an identical retrovirus causes arthritis. Arthritis has not been found in maedi-visna infected sheep. Two subacute spongiform encephalopathies of animals are shortly reviewed, scrapie in sheep and goats and transmissible mink encephalopathy (TME). General properties of the very unusual scrapie agent are mentioned briefly. The third type of a slow viral infection is mentioned, Aleutian mink disease, an immunopathological disorder of certain minks caused by a selective infection of lymphoid cells.

Aleutian Mink Disease↗

Composition and nutritive value of pejibaye (Bactris gasipaes) in animal feeds.

Nutritive assessment of pejibaye (Bactris gasipaes) meals included proximal composition of the lipid and nitrogenous fractions. Caloric values obtained as true metabolizable energy (TME) indicate that the pejibaye has a higher content of energy than corn and that it is not necessary to separate the seeds from the fruits in animal feeds; the level of indispensable aminoacids is considerably low, especially methionine, which is lower than in corn; thin layer chromatography shows that most of the free fatty acids are present in a ratio of 2:1 in unsaturated to saturated acids. The predominant fatty acids in whole pejibaye meal are oleic and palmitic acids with adequate levels of linoleic acid. Saturated fatty acids are predominant in the seed, with a very high content of lauric and myristic acids.

Amino Acids↗

[Mildewproof of Chinese traditional medicinal materials].

A study on the anti-mold activity of BCM, cinnamaldehyde and clove oil, was made by means of ultramicrostructural observation. The results show that both cinnamaldehyde and clove oil have strong anti-mold activity, (the former being even stronger), while BCM works well only in cases of Aspergillus, Penicillium and Trichoderma. SME and TME have found out that cinnamaldehyde is able to destroy the wall of fungal cells, the coagulate plasma and dissolve the cell organs.

Acrolein↗

[Ultrastructural changes in endothelial cells in rabbits with multiple organ failure (MOF)].

The morphological lesions of endothelial cells in rabbits with MOF were studied by scanning (SEM) and transmission electron microscopy (TME). The edges of the cells were blurred in the MOF groups. TEM showed that the nuclei were irregular and the mitochondria were swollen. The results indicated that the vascular endothelial cells were injured in rabbits with MOF in various extent. Administration of vitamin E in the early stage seemed beneficial in protecting the endothelial cell in this event.

Animals↗

A validity test of cephalometric variables as a measure of clinical applicability in anteroposterior profile assessment.

Twenty-six profile silhouettes are divided by five judges into three categories: retrognathic, orthognathic, and prognathic. On the corresponding lateral cephalograms, 51 cephalometric variables are tested for profile recognition. Discriminant analysis indicates that measurements based on natural head position perform better than comparable variables based on an intracranial reference line. The soft tissue variables (SnPo'-SnTV, Po'-SnTV, ILS-SnTV) are most successful, but no single variable is totally accurate. Skeletal variables relating the maxilla to the mandible (APo, AB, NA-PoA) are more successful than those variables relating one arch to the remainder of the skull (A-FHP, B-NTV, SNA, SNB). A combination of soft tissue and dental variables (SnPo'-SnTV, SnPo'-TMe', 1u-Npo, 1l-NPo) is found to be completely successful. A methodological approach, as applied in this study, can pinpoint the cephalometric variables that are clinically more effective in describing certain facial features.

Analysis of Variance↗

Regulation by retinoic acid of insulin-degrading enzyme and of a related endoprotease in human neuroblastoma cell lines.

Physiologically, the action of insulin-like growth factors (IGFs) is controlled at different levels, from its transcription start by tissue-specific and development-specific transcriptional factors to its degradation by peptidases such as insulin-degrading enzyme (IDE). Since IGF-II is the major autocrine/paracrine growth factor for neuroblastoma cells, we studied the expression and the role of IDE in this system. Here, we show that (a) IDE is expressed in several human neuroectodermal tumor cell lines, including neuroblastoma cell lines; (b) in a neuroblastoma cell line, IDE expression is up-regulated by retinoic acid, a well-known inducer of neuronal differentiation and/or programmed cell death; (c) IDE is probably not the only IGF-degrading enzyme present in these cells, since the activity of a novel thermolysin-like metalloendopeptidase, clearly distinct from IDE, is also detected. The TME activity is inhibited by IGF-I, Des-IGF-I, and IGF-II, and it is down-regulated by retinoic acid. Since retinoic acid plays a relevant role in controlling the growth of these cells and affects the expression of IDE, we have also: (a) identified the retinoic acid receptors (RARs) and retinoid X receptors (RXRs) expressed in these cell lines and (b) by means of synthetic retinoid analogues identified the RAR/RXR isoforms whose activation may be sufficient to induce the expression of the IDE gene. These results provide evidence that complex posttranslational molecular mechanisms participate in the autocrine/paracrine growth control of the IGF-II loop in neuroblastomas involving proteolytic systems.

Endopeptidases↗