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PubMed2003

SEL1L expression in pancreatic adenocarcinoma parallels SMAD4 expression and delays tumor growth in vitro and in vivo.

Recent data suggest that SEL1L may play an important role in pancreatic carcinoma, similar to breast cancer, where the expression of SEL1L has been associated with a reduction in both proliferative activity in vitro and clinical tumor aggressiveness. To investigate this possibility, we examined the expression of Sel1L in a series of primary pancreatic carcinomas by immunohistochemistry and characterized the effects of Sel1L overexpression both in vitro and in vivo. In 74 pancreatic cancers analysed, 36% lacked Sel1L expression, although there was no significant correlation between the expression of Sel1L and any clinicopathologic parameter, including survival. However, immunohistochemical reactivity for Sel1L and Dpc4/Smad4 was concordant in 69% of cases (chi(2) test P&<0.004). Overexpression of SEL1L in stably transfected pancreatic cancer cells caused both a decrease in clonogenicity and anchorage-independent growth as well as a significant increase in the levels of activin A and SMAD4. When implanted in nude mice, Suit-2-SEL1L-overexpressing clones displayed a considerably reduced rate of tumor growth. Thus, it can be hypothesized that Sel1L plays an important function in the growth and aggressiveness of pancreatic carcinoma. Moreover, our data provide evidence that SEL1L has an impact on the expression of genes involved in regulation of cellular growth, possibly through the TGF-beta signaling pathway.

Activins↗
PubMed2000

Endometriosis-associated intestinal tumors: a clinical and pathological study of 6 cases with a review of the literature.

This clinicopathologic study of primary Mullerian tumors of the bowel arising in foci of endometriosis is based on six new cases and an analysis of 17 previously reported cases. Varieties of Mullerian tumors occur in the bowel; the most common types are endometrioid carcinoma, followed by various mixed Mullerian tumors and stromal sarcomas. Seventy-eight percent develop in the rectosigmoid colon, the remaining in the cecum or ileum. Those in the latter area tend to be sarcomas or mixed Mullerian tumors. Certain architectural growth characteristics, derived from precursor endometriosis, are common to most endometriosis-associated intestinal tumors (EAITs). Seventy percent of EAITs occur in the outer bowel wall. Transmural tumors tend to form luminal polyps and assume an hourglass shape. Metachronous or synchronous Mullerian tumors occur in 39% of cases. Seventy percent of women with EAITs are in their mid 30s to early 50s. Common presenting symptoms are abdominal or pelvic pain, melena, and an abdominal or pelvic mass. Documented in 26% of patients is a history of prolonged unopposed estrogen therapy. Only 28.5% of cases die of their tumors, but follow-up is less than 5 years in all but 2 patients.

Adenofibroma↗
PubMed2001

Post-initiation effects of chlorophyllin and indole-3-carbinol in rats given 1,2-dimethylhydrazine or 2-amino-3-methyl- imidazo.

Chlorophyllin (CHL) is a water-soluble derivative of chlorophyll, the ubiquitous pigment in green and leafy vegetables, whereas indole-3-carbinol (I3C) is present in cruciferous vegetables such as cabbage, broccoli and cauliflower. In rats initiated with 1,2-dimethylhydrazine (DMH), CHL and I3C reportedly promoted or enhanced the incidence of colon tumors when they were administered after, or during and after the carcinogen exposure, respectively. The same compounds given post-initiation inhibited the formation of colonic aberrant crypts induced by heterocyclic amines, such as 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), but tumor suppression was not examined in the latter studies. In the present investigation, male F344 rats were treated with IQ or DMH during the first 5 weeks of a 1 year study; IQ was given in the diet (0.03%), whereas DMH was administered once a week by s.c. injection (20 mg/kg body wt). Beginning 1 week after the last dose of IQ or DMH until sacrifice, rats received 0.001, 0.01 or 0.1% (w/v) CHL in the drinking water or 0.001, 0.01 or 0.1% I3C in the diet. Compared with controls given carcinogen alone, 0.1% I3C treatment suppressed the multiplicity of IQ-induced colon tumors, and CHL inhibited in a dose-related manner the incidence of IQ-induced liver tumors. However, 0.001% CHL increased significantly the multiplicity of DMH-induced colon tumors while having no effect on the colon tumors induced by IQ. These results indicate that both the choice of carcinogen as well as the dose of the tumor modulator can be important determinants of the events that occur during post-initiation exposure to CHL or I3C. Based on the present findings and data in the literature, it is possible for CHL and I3C to act as tumor promoters or anticarcinogens, depending upon the test species, initiating agent and exposure protocol.

1,2-Dimethylhydrazine↗
PubMed1999

Endometrial cancers in postmenopausal breast cancer patients with tamoxifen treatment.

To evaluate possible predicting factors for endometrial cancer in postmenopausal breast cancer patients with tamoxifen treatment, we compared various clinical features between 12 postmenopausal breast cancer tamoxifen-treated patients with endometrial cancer and a control group of 261 otherwise similar patients without this endometrial pathology. These comparisons were based on a long-term prospective follow-up. Several clinical factors such as longer duration of breast disease, older patient age, lower frequency of chemotherapy administration, and higher frequency of postmenopausal bleeding were found among the tamoxifen-treated patients with endometrial cancers, and were significantly different when compared to the control group. Only eight (66.7%) had postmenopausal bleeding, and a preoperative diagnosis of endometrial cancer was made in only six (50.0%). When considering postmenopausal bleeding as a marker for endometrial cancer in the study patients, sensitivity was 67% and specificity was 98%.

Adenosarcoma↗
PubMed2003

Serous carcinoma arising in an adenofibroma of the endometrium.

A serous carcinoma and endometrial intraepithelial carcinoma were encountered in an endometrial adenofibroma in a 61-year-old woman. The carcinoma involved the myometrium and cervix (stage IIa). To our knowledge, this is the third documented case of an adenocarcinoma and the first serous carcinoma involving a uterine adenofibroma.

Adenofibroma↗
PubMed2004

Effective bladder sparing therapy with intra-arterial cisplatin and radiotherapy for localized bladder cancer.

PURPOSE: We evaluated the feasibility and efficacy of the organ preserving strategy of intra-arterial cisplatin and concurrent radiotherapy for localized bladder cancer. MATERIALS AND METHODS: Bladder preservation has been pursued over the decades in treatment regimens featuring radiotherapy alone or in conjunction with single or multiagent chemotherapy. The chemotherapy has consisted almost exclusively of intravenously administered drugs. There are theoretical and clinical data demonstrating a higher concentration of cisplatin within tumors following intra-arterial as opposed to intravenous delivery. This study was performed to evaluate whether this increased concentration would enhance radiosensitization and thereby increase the success of bladder preservation. RESULTS: We report on our prospectively collected experience during 15 years of treating 200 patients with localized bladder cancer using this regimen of 3 courses of intra-arterial cisplatin integrated with pelvic radiotherapy and reserving cystectomy for salvage as required. We report on the efficacy in terms of complete response rate, ultimate tumor-free bladder preservation, overall survival and patterns of failure. We detail the acute and chronic toxicity observed to date. CONCLUSIONS: This strategy has resulted in a durable high complete response rate and overall tumor-free bladder preservation rate of 75% while maintaining a survival comparable to that achieved with cystectomy. These results corroborate the hypothesis that intra-arterial administration of cisplatin enhances radiosensitization during pelvic radiotherapy.

Adenosarcoma↗
PubMedDate not supplied

Ultrasonography of the medial iliac lymph nodes in the dog.

Sixty-one medial iliac lymph nodes of 38 different dogs (eight with adenocarcinoma of the apocrine glands of the anal sac, 13 with multicentric lymphoma, six with multicentric lymphoma but in clinical remission, and 11 control dogs) were evaluated to assess the ability of ultrasound to identify and interrogate these lymph nodes across the different groups and to differentiate these groups using different sonographic parameters. Ultrasound proved to be useful to assess canine medial iliac lymph nodes. An increase in size or number of detected lymph nodes or finding rounder or heterogeneous lymph nodes could differentiate lymph nodes of dogs of the control group from lymph nodes of dogs with lymphoma or an adenocarcinoma of the apocrine glands of the anal sac. Subcategories of malignancy could not be differentiated. More studies need to be performed, both with patients with reactive lymph nodes and also focusing on other canine superficial lymph nodes, before generalizing the results of this study to other areas or diseases.

Adenosarcoma↗
PubMed2003

Chromosomal variations within aneuploid cancer lines.

Aneuploid cancers exhibit a wide spectrum of clinical aggressiveness, possibly because of varying chromosome compositions. To test this, karyotypes from the diploid CCD-34Lu fibroblast and the aneuploid A549 and SUIT-2 cancer lines underwent fluorescence in situ hybridization (FISH) and DAPI counterstaining. The number of DAPI-stained and FISH-identified chromosomes, 1-22, X,Y, as well as structural abnormalities, were counted and compared using the chi(2), Mann-Whitney rank sum test and the Levene's equality of variance. Virtually all of the evaluable diploid CCD-34Lu karyotypes had 46 chromosomes with two normal-appearing homologues. The aneuploid chromosome numbers per karyotype were highly variable, averaging 62 and 72 for the A549 and SUIT-2 lines, respectively. However, the A549 chromosome numbers were more narrowly distributed than the SUIT-2 karyotype chromosome numbers. Furthermore, 25% of the A549 chromosomes had structural abnormalities compared to only 7% of the SUIT-2 chromosomes. The chromosomal compositions of the aneuploid A549 and SUIT-2 cancer lines are widely divergent, suggesting that diverse genetic alterations, rather than chance, may govern the chromosome makeups of aneuploid cancers.

Adenosarcoma↗
PubMed1998

CT and MRI appearances of sarcomatous change in chronic pelvic endometriosis.

Endometriosis is a relatively common condition in pre-menopausal women. Rarely, endometrial malignancy may arise in and co-exist with endometriosis. In this case report, the findings on CT and MRI which indicated this development are described. Multiple image-guided biopsies showed features consistent with endometriosis and the diagnosis was not confirmed histopathologically until formal laparotomy and open biopsy.

Adenosarcoma↗
PubMed1997

Serum insulin-like growth factors (IGFs) and IGF binding protein (IGFBP)-3 in patients with gastric cancer: IGFBP-3 protease activity induced by surgery.

Recent findings have indicated that insulin-like growth factors (IGF-I and IGF-II) may play a role in neoplasia. Alteration of serum IGFs or IGF Binding Proteins (IGFBPs) have been reported in some tumors. In this study, we measured serum IGF-I, IGF-II and IGFBPs profile in gastric cancer by radioimmunoassay and Western ligand blots. The serum IGF-I level in gastric cancer was significantly lower than in control subjects (65.2 +/- 26.5 vs 148.4 +/- 55.2 ng/ml, p < 0.01) and was further decreased to 45.5 +/- 20.9 ng/ml after surgery. The serum IGF-II level was slightly higher than that in control subjects (826.3 +/- 360.2 vs 735.7 +/- 154.6 ng/ml) but it was significantly decreased after surgery (525.7 +/- 220.1 ng/ml, p < 0.05). The serum IGFBP-3 level was not significantly different from those in control subjects. However, we observed a decreased level of serum IGFBP-3 after surgery, and incubation of postoperative serum with control serum resulted in a significant reduction of IGFBP-3 level. The reduction of IGFBP-3 in postoperative serum was mainly due to surgery associated IGFBP-3 protease activity. This protease activity was totally inhibited by aprotinin, EDTA and PMSF but not by pepstatin and leupeptin. This inhibition pattern is consistant with cation dependent serine protease. We speculate that proteolysis of IGFBP-3 may contribute to increase the bioavailability of IGFs.

Adenosarcoma↗
PubMed2000

Pancreatic duct cell carcinoma with positive 111In Octreotide uptake.

Duct cell adenocarcinomas may produce neuroendocrine markers such as pancreatic polypeptide, gastrin and gastrin releasing hormones. A 53 year old patient, with a history of insulin dependent diabetes, was found to have a pancreatic mass which was later pathologically demonstrated to be a duct cell adenocarcinoma. The tumor produced elevated circulating neuroendocrine markers specifically gastrin and pancreatic polypeptides. An 111In Octreotide imaging showed definite uptake of Octreotide by the tumor. The patient was subsequently treated with Somatostatin analog which resulted in the reduction of some of the circulating endocrine markers. The patient had essentially six months of asymptomatic clinical remission but then she relapsed. Octreotide scanning could be useful for selected patients with pathologic diagnosis of duct cell adenocarcinoma, because some tumors may have neuroendocrine features and can be imaged, and might even respond to Somatostatin analog therapy.

Adenosarcoma↗
PubMed1991

Effects of hypergravity on adherent human cells.

In recent years, accumulating evidence has shown that microgravity or hypergravity may affect cell growth and differentiation. Since it is not easy to carry out researches in space or to simulate weightlessness on earth, we conducted experiments on simulated hypergravity (2 to 15 g) by using a centrifuge (radius: 80 cm; speed motor: 180 rpm). We looked for the effects of chronic hypergravity (7 to 10 days) on cultures of three human cell lines: lung or dermic fibroblasts and lung adenocarcinoma A 549 cells. The results showed a significant decrease (10-20%, P<0.05) in cell proliferation connected to a significant decrease (20-50%, P<0.01) in culture DNA content under hypergravity, but only for lung fibroblasts. The protein content was never disturbed. Dermic fibroblast elastase activity was enhanced (8-13%, P<0.02) under 15 g. Total phospholipid content as well as relative amounts of phospholipid components, analysed by thin layer chromatography, were unchanged in A 549 cells.

Adenosarcoma↗
PubMed2001

[Evaluation and treatment of endometrial cancer].

Endometrial cancer is the most common gynaecologic cancer and its incidence increases with age. Prognosis is good because in over 80% of cases the cancer is discovered early. Preoperative work-up should include definition of the operability of such patients, who are often elderly with frequent co-morbidity. Preoperative evaluation and operative findings allow guiding the treatment and evaluating the prognosis. Main determinants are local extension, penetration into the myometrium, histologic stage of the tumour and involvement of lymph modes or peritoneum. Surgery is the first approach since it establishes the evaluation and comprises the first step of treatment. When necessary, subsequent treatment uses irradiation. Treatment with hormones or antimitotic drugs is less effective and is used for forms that are locally advanced, metastatic or recurrent after initial treatment.

Adenosarcoma↗
PubMed2003

Effect of Nigella sativa (N. sativa L.) and oxidative stress on the survival pattern of MCF-7 breast cancer cells.

N. Sativa L., an oriental spice, has long been used as a natural medicine for treatment of many acute as well as chronic conditions. It has been used in the treatment of diabetes, hypertension, and dermatological conditions. There has been very few studies on the effects of N. Sativa as cancer prevention/therapy. Our objective therefore, was to expose MCF-7 breast cancer cells to aqueous and alcohol extracts and in combination with H2O2 as an oxidative stressor. Measurement of cell survival under various concentrations and combinations was conducted using standard cell culture techniques, exposure protocols in 96 well plates and Fluoro-spectrosphotometry. Following cellular growth to 90% confluency, exposure to water (WE) and ethanol (AE) extracts of N. sativa and H2O2 was performed. Toxicity index (LC50) was calculated from percent survival using regression analysis. Results showed that the alcohol extract and its combinations were able to completely inactivate the MCF-7 cells (LC50 ranged from 377.16-573.79 in descending potency for H2O2 + AE, AE and Mix of WE and AE). H2O2 alone effectively inactivated MCF-7 cells (LC50 = 460.94). The least effective combinations in descending potency were WE + H2O2, WE + AE + H2O2, and WE (LC50 were 725.79, 765.94, and 940.5 respectively. Combinations other than AE + H2O2 showed possible interactions, which lead to reduction in their potency. In conclusion, N. Sativa alone or in combination with oxidative stress were found to be effective in vitro in inactivating MCF-7 breast cancer cells, unveiling opportunities for promising results in the field of prevention and treatment of cancer.

Adenosarcoma↗
PubMed2004

Different muscarinc receptors are involved in the proliferation of murine mammary adenocarcinoma cell lines.

We described that two different murine mammary adenocarcinoma cell lines, LM3 and LM2 constitutively expressed muscarinic acetylcholine receptors (mAchR). We here demonstrate, by competitive binding experiments with the tritiated muscarinic antagonist quinuclidinyl benzilate that M2 subtype predominates in both tumor cell lines. Concordantly immunoblotting assays indicate that mAchR exhibit the following order of expression: M2 > M4 > M3 > M1 >> M5 in both tumor cell lines. Activation of mAchR with carbachol (CARB) increased proliferation in both tumor cell lines in a concentration dependent manner. In LM3 cells CARB promoted proliferation via M3 receptor activation via inositol 1,4,5-triphosphate and nitric oxide production. CARB-induced LM2 cells proliferation needed both M2 and M1 receptor activation, promoting prostaglandin E2 liberation and arginase catabolism respectively, both of them involved in tumor cell growth.

Adenosarcoma↗