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About 10% of all serous ovarian cancer has BRCA1 and/or BRCA2 mutations. Recent data showed that following the SEE FIM protocol it is possible to evidence more fimbriae cancers. Due to those studies, fallopian tube cancer in recent years has become the predominant site of cancer in BRCA1 and/or 2 mutation carriers. The pathological study of the fallopian tube is not complete during salpingo-oophorectomy because a small part (intramural site) is situated inside the uterus. In this case report we demonstrate how it is possible to remove the tubes entirely for pathological analysis without hysterectomy by laparoscopic surgery.

Objectives: To evaluate PCa incidence in patients with one or more negative extended prostate biopsy who underwent repeat biopsy or TURP., Material and Methods: From June 2003 to February 2008, 308 patients were submitted to repeat prostate biopsy (median 20.5 cores) and 120 patients underwent TURP after one or more 12 cores prostate biopsy. Indications for biopsy were: abnormal DRE; PSA > 10 ng/mL; PSA included between 4.1-10 or 2.6-4 ng/mL with free/total PSA < or = 25% and < or = 20%, respectively 262 and 46 underwent a second and a third biopsy: 218 because for high levels of PSA, 40 and 50 patients for a previous diagnosis of HGPIN and ASAP, 28 had an abnormal DRE. PSA in patients who underwent TURP was 11.6 ng/mL (median); in all cases DRE was negative and only 76 patients referred LUTS., Results: PCa incidence at repeat biopsy was 16.9%; 96.2% of cancers were diagnosed at a second biopsy and 3.8% at a third one. PCa incidence was higher in patients with previous ASAP (43.4% and 50%) vs patients with HGPIN (25% and 0%) or benign pathology (11.9% and 0%). PCa was diagnosed in 11.1% and 19% of patients who underwent TURP previously submitted to a first and a second biopsy, respectively., Conclusions: In case of persistent suspicion of PCa after a repeated negative saturation biopsy, TURP should be proposed as part of the diagnostic procedure aside from LUTS, especially in patients with a life expectancy greater than 10 years.

PURPOSE We aimed to identify the maximum-tolerated dose (MTD) of irinotecan in patients with cancer with UGT1A1*1/*1 and *1/*28 genotypes. We hypothesize that the patients without the *28/*28 genotype tolerate higher doses of irinotecan. PATIENTS AND METHODS Patients undergoing first-line treatment for metastatic colorectal cancer (CRC) eligible for treatment with irinotecan plus infusional fluorouracil/leucovorin (FOLFIRI) were screened for the UGT1A1*28/*28 genotype and excluded from the study. Fifty-nine white patients with either the *1/*1 or the *1/*28 genotype were eligible for dose escalation of irinotecan. The starting dose of biweekly irinotecan was 215 mg/m(2) for both genotype groups, whereas the dose of infusional fluorouracil was fixed. Pharmacokinetic data of irinotecan and metabolites were also obtained. Results The dose of irinotecan was escalated to 370 mg/m(2) in patients with the *1/*28 genotype and to 420 mg/m(2) in those with the *1/*1 genotype. Dose-limiting toxicities (DLTs) were observed in two of four of *1/*28 patients at 370 mg/m(2) and in two of three of *1/*1 patients at 420 mg/m(2). No DLTs were observed in 10 *1/*28 patients at 310 mg/m(2) and in 10 *1/*1 patients at 370 mg/m(2); hence these dose levels were the MTD for each genotype group. The most common grade 3 to 4 toxicities were neutropenia and diarrhea. The pharmacokinetics of irinotecan and SN-38 exhibit linear kinetics. CONCLUSION The recommended dose of 180 mg/m(2) for irinotecan in FOLFIRI is considerably lower than the dose that can be tolerated when patients with the UGT1A1*28/*28 genotype are excluded. Prospective genotype-driven studies should test the efficacy of higher irinotecan doses in the FOLFIRI schedule.

Abdominal abscess is a very important problem nowadays, being responsible for prolonged hospitalisation, because these infections still cause substantial morbidity and mortality. For many years, surgical drainage has been considered the best therapeutic option in abdominal abscesses but several studies have subsequently shown that the percutaneous approach is as effective as surgical drainage. Starting from this background, the aim of this study was to evaluate whether or not percutaneous drainage is a valid treatment of choice. In the Department of Surgical Sciences, Organ Transplantation and Advanced Technologies of the University of Catania, 451 ultrasound guided percutaneous drainages of intra-abdominal abscesses were performed on 430 patients. Abscess drainage was successful in 322/403 (80%) of postoperative abscess, in 16/18 (90%) of primitive abscesses, in 10/12 cases (85%) of acute cholecystitis, in 3/6 cases (50%) of intrahepatic abscess and in 12/12 cases (100%) of pyelonephritis. US-guided drainage is currently the gold standard in the treatment of simple abdominal abscesses.

Background: The enhancement of circulating endothelial progenitor cells (EPCs) obtained by exercise training can be beneficial to patients with cardiac disease. Changes in the levels and differentiation of CD34(pos)/KDR(pos) EPCs, as well as the plasma concentration of vascular endothelial growth factor (VEGF) and stromal cell-derived factor (SDF)-1 EPC-mobilizing cytokines, were evaluated in patients with chronic heart failure after 8 weeks of supervised aerobic training (SAT) and 8 weeks of subsequent discontinued SAT (DSAT)., Methods and Results: The levels of circulating EPC and EPC differentiation potential of 22 patients who underwent SAT were studied by fluorescence-activated cell sorter analysis and colony forming-unit assay, respectively. The plasma levels of VEGF and SDF-1 were measured by enzyme-linked immunosorbent assay. In response to SAT, the levels of both EPC and VEGF/SDF-1 markedly increased (P < .001 vs baseline) but returned to the baseline levels after DSAT. A similar change was observed with the EPC clonogenic potential, but on DSAT the baseline level was incompletely attained., Conclusions: In response to SAT, patients with chronic heart failure show enhanced EPC levels and clonogenic potential that is mirrored by increased plasma VEGF and SDF-1 levels. DSAT can interfere with the maintenance of training-acquired VEGF/SDF-1-related EPC levels and clonogenic potential.

Background: RT-PCR has been widely used for the analysis of gene expression in many systems, including tumor samples. GAPDH (Glyceraldehyde-3-phosphate dehydrogenase) has been frequently considered as a constitutive housekeeping gene and used to normalize changes in specific gene expression. However, GAPDH has been shown to be up-regulated in many cancers and down-regulated by chemotherapic drugs. Bisphosphonates, potent inhibitors of bone resorption, have recently shown a direct and indirect antitumor effect in vitro and in animal models. They exert their effects mainly by inhibiting the mevalonate pathway but also by modulating the expression of many genes not only in osteoclasts but also in cancer cells., Methods: We evaluated GAPDH gene expression by real time RT PCR in breast (MCF-7 and T47D) and prostate (PC3 and DU-145) cancer cell lines treated with amino and non-amino bisphosphonates., Results: Our results showed that amino-bisphosphonates significantly decrease in a dose-dependent manner the expression of GAPDH gene., Conclusion: Therefore, GAPDH is inaccurate to normalize mRNA levels in studies investigating the effect of bisphosphonates on gene expression and it should be avoided. On the other hand, this gene could be considered a potential target to observe the effects of bisphosphonates on cancer cells.

Background: Intramyocardial injection of autologous bone marrow (ABM) may induce angiogenesis. We tested the safety and feasibility of catheter-based direct percutaneous intramyocardial delivery of ABM in patients with refractory angina pectoris., Methods: Ten patients (9 men, 67 +/- 8 years) with refractory angina (Canadian Cardiovascular Society class III-IV) and documented myocardial ischemia were enrolled. After left ventricular electromechanical mapping, freshly aspirated and filtered ABM was percutaneously injected into target myocardial ischemic areas. Clinical symptoms (as assessed according to the Canadian Cardiovascular Society class), quality of life, and myocardial perfusion were evaluated before the procedure and through the follow-up., Results: In all patients, ABM was successfully injected into the target regions. No periprocedural complications occurred. At 12 months, no major cardiac events (death, acute myocardial infarction, stroke, and malignant ventricular arrhythmias) occurred. Severity of angina improved of > or = 2 classes in 3 patients. Quality of life showed a significant improvement in all patients. Myocardial perfusion in the target regions improved in 4 of 8 patients., Conclusions: Direct percutaneous intramyocardial delivery of ABM appears feasible and safe. Further evaluation is warranted to test its clinical efficacy.

Purpose: To study the prognostic value for overall survival of baseline assessment of functional status, comorbidity, and quality of life (QoL) in elderly patients with advanced non-small-cell lung cancer treated with chemotherapy., Patients and Methods: Data from 566 patients enrolled onto the phase III randomized Multicenter Italian Lung Cancer in the Elderly Study (MILES) study were analyzed. Functional status was measured as activities of daily living (ADL) and instrumental ADL (IADL). The presence of comorbidity was assessed with a checklist of 33 items; items 29 and 30 of the European Organisation for Research and Treatment of Cancer (EORTC) core questionnaire QLQ-C30 (EORTC QLQ-C30) were used to estimate QoL. ADL was dichotomized as none versus one or more dependency. For IADL and QoL, three categories were defined using first and third quartiles as cut points. Comorbidity was summarized using the Charlson scale. Analysis was performed by Cox model, and stratified by treatment arm., Results: Better values of baseline QoL (P = .0003) and IADL (P = .04) were significantly associated with better prognosis, whereas ADL (P = .44) and Charlson score (P = .66) had no prognostic value. Performance status 2 (P = .006) and a higher number of metastatic sites (P = .02) also predicted shorter overall survival., Conclusions: Pretreatment global QoL and IADL scores, but not ADL and comorbidity, have significant prognostic value for survival of elderly patients with advanced non-small-cell lung cancer who were treated with chemotherapy. Using these scores in clinical practice might improve prognostic prediction for treatment planning.

Bisphosphonates are important in the management of tumours with secondary bone involvement. Recent findings have suggested that these drugs also have an effect on primary tumour burden. Telomerase is a cellular ribonucleoprotein reverse transcriptase responsible for elongation of the telomere. Telomerase expression is increased in many cancers. We studied the direct effects of clodronate, alendronate, and pamidronate (from 10(-6) to 10(-4) M) on MCF-7 human breast cancer cell line. In particular, we investigated their effect on viability, proliferation, apoptosis, human telomerase reverse transcriptase expression (h-TERT) by RT-PCR and telomerase activity. Alendronate and pamidronate showed an inhibition of viability (-63 and -35%, respectively; p < 0.0001) and proliferation of cancer cells, while no effect was observed with clodronate. Amino-bisphosphonates induced a significant increase of apoptosis in MCF-7. In addition, they showed a significant decrease in telomerase expression and activity with respect to control and to clodronate.

Aim of the Study: To evaluate if percutaneous ethanol injection treatment, introduced twelve years ago as palliative therapy for inoperable hepatocellular carcinoma, can be used with curative intent to treat biliary cysts with good results., Materials and Methods: For the study were observed 13 symptomatic patients (M 4; F 9 - age 38-71, medium 54 years). All the patients were treated by percutaneous alcoholization under ultrasonographic control., Results: Better technique and protocol standardisation give us the possibility to utilise percutaneous ethanol injection like a good treatment for symptomatic patients., Conclusions: Easy technique, low cost and very small number of complications gives to percutaneous ethanol injection the possibility to become the gold standard for the treatment of biliary cysts.

Aim of this study was to evaluate the role of radiofrequency ablation in the treatment of the hepatic metastasis of colorectal cancer. From November 1997 to July 2002 49 radiofrequency ablations have been performed in 19 patients (11 male and 8 female; mean age 65 years: range 50-78 years). The disease-free period was between 5 and 32 months. Nodules had a diameter <3 cm in 4 cases while in 3 cases a single lesion was present. One patient had a single lesion after 2 courses of intravenous systemic chemotherapy which had a reduced greater lesion (from 6 to 3 cm) while a 2 cm lesion had disappeared. In the remaining 12 patients the mean number of lesions is 3 (range 1-13) with a diameter between 3 and 12 cm. The radiofrequency ablation has been performed during laparotomy and vascular exclusion through clampage of the liver hilum in 4 cases and percutaneously under ultrasound guide in the remaining 15 cases. All patients underwent follow up by computed tomography, CEA level and ultrasound every 3 months. One patient only has completed a 4 year follow up and is alive without local recurrence but with a cerebral metastasis. The other 18 patients have a 32 months follow up with a survival of 50% (9 on 18). In conclusion in our experience the radiofrequency ablation is a valid alternative method in the treatment of the hepatic metastasis of colorectal cancer.

The present study describes supportive care (SC) in patients with advanced non-small-cell lung cancer (NSCLC), evaluating whether it is affected by concomitant chemotherapy, patient's performance status (PS) and age. Data of patients enrolled in three randomised trials of first-line chemotherapy, conducted between 1996 and 2001, were pooled. The analysis was limited to the first three cycles of treatment. Supportive care data were available for 1185 out of 1312 (90%) enrolled patients. Gastrointestinal drugs (45.7%), corticosteroids (33.4%) and analgesics (23.8%) were the most frequently observed categories. The mean number of drugs per patient was 2.43; 538 patients (45.4%) assumed three or more supportive drugs. Vinorelbine does not produce substantial variations in the SC pattern, while cisplatin-based treatment requires an overall higher number of supportive drugs, with higher use of antiemetics (41 vs 27%) and antianaemics (10 vs 4%). Patients with worse PS are more exposed to corticosteroids (42 vs 30%). Elderly patients require drugs against concomitant diseases significantly more than adults (20 vs 7%) and are less frequently exposed to antiemetics (12 vs 27%). In conclusion, polypharmacotherapy is a relevant issue in patients with advanced NSCLC. Chemotherapy does not remarkably affect the pattern of SC, except for some drugs against side effects. Elderly patients assume more drugs for concomitant diseases and receive less antiemetics than adults.

Portal vein thrombosis usually appears in the course of acute abdominal septic complications or after splenectomy, though in 50% of cases no aetiological factors can be identified. In our department we recently treated two patients affected by portal vein thrombosis, the first after splenectomy for haematological disease, and the second after sigmoid diverticulitis. When portal vein thrombosis occurs after splenectomy for haematological reasons, the increased viscosity of the blood due to thrombocytosis is the main factor regarded as being the cause. In the first case, acute abdominal pain appeared 15 days after splenectomy and the diagnosis was suspected and confirmed by Doppler ultrasonography. The clinical course in the second case was less typical, because, although the sigmoid diverticular disease was known, the symptomatology presented with high fever but no clear subjective or objective abdominal picture. The diagnosis was achieved by computed tomography. The clinical picture may vary greatly but usually abdominal pain, fever and intestinal ischaemia are present. Nowadays the diagnosis has improved as a result of the extensive use of Doppler ultrasonography and computed tomography. Fibrinolytic therapy and acetylsalicylic acid are the treatment of choice and in our experience the clinical picture tends to clear up rapidly. When the patient presents a number of risk factors, prophylaxis of portal vein thrombosis should be planned.

The aim of this study was to verify, and possibly improve, culture conditions to expand human mobilized peripheral blood stem cells (PBSCs). We investigated the role of three parameters: A) the culture medium (serum-free versus serum-dependent); B) the initial cell population (Ficoll-separated mononucleated cells versus CD34(+)-selected cells), and C) the low concentration of recombinant cytokines, flt3 ligand, and thrombopoietin in association with a basic cocktail of stem cell factor, interleukin (IL)-6, IL-3, GM-CSF, and erythropoietin. Eighteen leukapheresis samples were monitored in static culture for 15 days. The expansion potential was assessed at day 10 and 15 by total nuclear cells, colony-forming-units (CFUs) (burst-forming units-erythroid [BFU-E], colony-forming units-granulocyte-macrophage [CFU-GM], and colony-forming units-granulocyte-erythroid-macrophage-megakaryocyte [CFU-GEMM]), and flow cytometry immunophenotyping (CD34(+)/CD38(-), CD38(+), CD33(+), CD41(+), GlyA(+) progenitor cells). The results, evaluated by multivariate analysis of variance, emphasize that some variables affected the outcome of stem and progenitor cell expansion. CD34(+) enrichment increased expansion of total nuclear cells, number of CD38(+) and CD33(+) late precursors, and number of the CFU-GM compartment. Interestingly, however, quantitative expansion of GlyA(+) and the early progenitor cells (CD34(+)/CD38(-), CFU-GEMM, BFU-E) are favored by the use of unselected mononucleated cells. Regarding the role of serum, no significant difference was observed except for expansion of total nuclear cells, CFU-GM, and BFU-E. Cytokine combinations, in particular the use of flt3 ligand, stimulated expansion of almost all the cellular subsets, reaching a statistical significance for total nuclear cells and CFU-GM. Our study indicates that progenitor and late precursor multilineage cell compartments of mobilized PBSCs may be significantly expanded in short-term cultures by well-defined experimental conditions. Furthermore, these data might be useful when evaluating ex vivo expansion of hematopoietic cells for clinical purposes.

Background: Capillarisation of hepatic sinusoids is a well recognized phenomen occurring in long standing liver disease, in hepatic cirrhosis as well as in hepatocellular carcinoma. To study immunohistochemically the expression and distribution of CD34 in chronic liver disease and hepatocellular carcinoma in order to evaluate the possible diagnostic implication of this marker., Methods: Sixty-five samples of liver tissue showing normal liver, different degrees of chronic inflammation, cirrhosis and histological features of hepatocellular adenoma and carcinoma (HCC) were included in the study. The specimens were fixed in formalin and embedded in paraffin and an immunohistochemical investigation was performed by the standard avidin-biotin-peroxidase complex method with CD34., Results: The sinusoids of normal liver showed no immunoreactivity. The sinusoids of liver affected by different degrees of chronic active hepatitis showed no or focal immunostaining for CD34; an increased immunoreactivity was observed in the periportal sinusoids of the cirrhotic nodules whereas diffuse and strong staining was observed in the overall HCC as well as in the hepatocellular adenoma tested., Conclusions: In HCC, immunoreactivity for CD34 represents an effective method to evaluate angiogenesis and to distinguish well-differentiated HCC from non-neoplastic liver. Its role in clinical stage and prognostic evaluation needs further investigation.

The telomerase activity and the senescence profile of cultured breast fibroblasts from normal human interstitial and malignant stromal tissue were studied in comparison with their proliferation and differentiation pattern. Fibroblasts were grown either in the presence or absence of a conditioned medium (CM) obtained from cultures of the oestrogen receptor-positive breast cancer MCF-7 cell line. At different passages (from the 2nd up to the 48th), fibroblasts were examined for the telomerase activity by the Telomerase Repeats Amplification Protocol (TRAP) assay, for proliferation profile by Ki-67 antigen expression, and the myofibroblast or smooth muscle cell-like differentiation pattern by immunofluorescence with monoclonal antibodies specific for smooth muscle markers. Serial passages of fibroblasts from normal or tumour breast reveal that the relationship between the levels of telomerase activity and phenotypic/proliferation profile changes with cell subcultivation in a different manner in the two cell populations. The fibroblasts from normal tissue completed 12 passages in a CM-independent way prior to senescence whereas fibroblasts from tumour stroma senescence were attained after 48 passages. These cells showed a marked decrease of telomerase activity, growth rate and smooth muscle alpha-actin expressing myofibroblasts after the 32nd passage. CM treatment of this fibroblast population induces a decline in the myofibroblast content, which precedes the changes in telomerase activity. Passaged fibroblasts from normal breast tissue can be converted to myofibroblasts upon CM treatment whereas those from tumour stroma were CM-insensitive. Taken together our data suggest that a heterogeneous fibroblast population with different life span is activated/recruited in the breast interstitium and poses the problem of a unique activation/recruitment of fibroblasts in neoplastic conditions.

We studied the effect of conditioned medium (CM) obtained from cultures of oestrogen-receptor positive breast cancer MCF7 cell line on the differentiation, proliferation and apoptosis patterns of cultured breast fibroblasts from normal interstitial and malignant stromal tissue. Fibroblasts were grown in the presence or absence of CM and examined for the differentiation pattern by immunofluorescence and Western blotting procedures, for proliferation profile by Ki67 expression, and for apoptosis by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling technique. Monoclonal antibodies specific for non-muscle (NM), smooth muscle (SM) lineage and differentiation markers were applied to these cultures. CM is able to induce a SM-like differentiation in interstitial fibroblasts, i.e., essentially myofibroblast formation. Fibroblasts from tumour stroma showed the presence of a small number of smooth muscle cells (SMC) along with a large number of myofibroblasts. Treatment of these cultures with CM was unable to change this pattern. Only normal fibroblasts were responsive to the proliferation/apoptotic-inhibitory effect of the CM. These data suggest that structural and functional differences exist between stromal fibroblasts from normal breast and breast cancer with respect to the responsiveness to soluble factors present in the CM. We hypothesize that the lack of in vitro sensitivity to CM shown by 'tumour' fibroblasts is the result of an in vivo inherent and stable phenotypic change on the fibroblasts surrounding breast tumour cells occurring via a paracrine mechanism.

Aims and Background: In addition to nausea and vomiting following chemotherapy treatment, cancer patients can experience these side effects prior to a treatment session, the so-called anticipatory nausea and vomiting. As various psychological and neurophysiological aspects have been claimed to be implied in its etiopathogenesis, the present paper aims to shortly review the etiological, epidemiological and therapeutical assumptions on the topic, in particular the psychological-behavioral therapies., Patients and Methods: The present study was carried out on 16 consecutive adult cancer patients affected by chemotherapy-induced anticipatory nausea and vomiting who had received at least four treatment cycles. All of them were submitted to induction of relaxation followed by hypnosis., Results: In all subjects anticipatory nausea and vomiting disappeared, and major responses to chemotherapy-induced emesis control were recorded in almost all patients., Conclusions: The experience highlights the potential value of hypnosis in the management of anticipatory nausea and vomiting; furthermore, the susceptibility to anticipatory nausea and vomiting is discussed under the psychoanalytic point of view., (Copyright 2000 S. Karger AG, Basel.)

Introduction: We investigated the accuracy of contrast-enhanced color Doppler US in the assessment of the effectiveness of intralesional treatment of hepatocarcinomas., Material and Methods: Eight cirrhotic patients (HCV+), Child-Pugh class B, with a single hepatocarcinoma (< 4 cm O) and ineligible for surgical resection for various reasons (age > 70 years, reduced partial hepatic reserve, esophageal varices at risk, postoperative recurrence, no consent to the operation) were submitted to radiohyperthermia (6 patients) and percutaneous alcoholization (2 patients). The diagnosis was made with alpha-fetoprotein titration. CT, B-mode and color Doppler US with the administration of Levovist (Schering AG, Berlin, Germany). Thirty and 60 days after the treatment, both the alpha-fetoprotein titration and contrast-enhanced color Doppler US were repeated., Results: Baseline color Doppler was carried out before intralesional treatment in the 8 patients and was followed by Levovist color Doppler which showed some intralesional signals, afferent vessels and rich vascularization in all the lesions. At the first follow-up (30 days), no intralesional vascular signals or afferent vessels were detected in any patient, while rich peripheral vascularization persisted in all cases, even after radiofrequency and alcoholization treatments. At 60 days' follow-up, the color Doppler pattern of all cases was the same as at 30 days., Conclusions: The absence of any intralesional vascular signals in all the treated patients and the possible demonstration of complete tumor necrosis seem to confirm the important role of contrast-enhanced color Doppler US in monitoring focal hepatic lesions after intralesional treatment.

A comparative analysis of the differentiation pattern, the proliferative behaviour, and the level of apoptosis between human benign and malignant neoplasms of smooth-muscle (SM) tissue is lacking. The clinical, histopathological, immunochemical, and immunocytochemical features of leiomyomas (LM) and leiomyosarcomas (LMS) were investigated by a panel of monoclonal antibodies specific for some differentiation markers of SM tissue (SM myosin and alpha-actin, desmin, and SM22) and for markers of non-muscle tissue (vimentin and non-muscle myosin). Proliferating normal and neoplastic cells were identified by proliferating-cell nuclear antigen (PCNA)/Ki67 immunostainings and the apoptotic cells were revealed by means of the terminal-deoxynucleotidyltransferase-mediated dUTP nick-end labelling technique. Gel electrophoresis and Western blotting, performed with anti-(SM1/SM2 myosin isoform) antibody, indicated quantitative differences between LMS and LM, which mirrored higher positive to negative nuclear ratios for PCNA, Ki67 and apoptosis in malignant as opposed to benign neoplasms. With LM, however, a similar SM1 to SM2 ratio could be associated with different proliferation levels. Uterine, gastric and intestinal LMS displayed specific patterns of SM1/SM2 and/or non-muscle myosin expression that were not paralleled by different levels of proliferation/apoptosis. While the level of PCNA/Ki67 correlated with the level of apoptosis in normal SM tissues and LM, that of LMS did not. In vivo at the cellular level, LM and uterine LMS displayed a near-uniform SM tissue differentiation, whereas the other LMS displayed a lesser or a heterogeneous immunoreactivity. In vitro, cultured LMS cells showed a limited and peculiar expression of SM myosin. In conclusion, there is no reciprocal relationship between degree of differentiation and the level of proliferation, as exemplified by the finding that the less differentiated intestinal LMS displays the lowest proliferative behaviour and that the relatively more differentiated gastric LMS/metastasis is more proliferative.

The putatative effects of different estrogen levels on the expression of non-muscle myosin isoforms in rabbit myometrium have been investigated using three monoclonal anti-platelet myosin heavy chain (MyHC) antibodies (NM-F6, NM-G2, and NM-A9). Western blotting analysis of proteolytic digests of human platelet actomyosin indicates that these antibodies are specific for three distinct epitopes. Comparative immunofluorescence tests on cultered human fibroblasts with polyclonal sequence-specific anti-MyHCA antibody suggest that the patterns of NM-F6, NM-.G2 and NM-A9, although similar, do not overlap with that of type-A MyHC. Distribution of NM myosin isoforms has been studied in indirect immunofluorescence assays using cryosections of tissues from rabbits at various stages of development, pregnancy, or from ovariectomized, 17beta-estradiol-treated ovariectomized, and human chorionic gonadotropin-treated animals. Non-muscle myosin antigenicity is still present in the myometrium when the female becomes sexually competent. The immunoreactivity of non-muscle myosin for NM-F6 is steroid-independent, since it does not change with pregnancy or ovariectomy, but that of NM-G2 is estrogen-dependent; the latter disappears during pregnancy and in ovariectomized animals treated with estradiol, whereas it is expressed in ovariectomized rabbits. Although non-muscle myosin immunoreactivity for NM-A9 is detectable under all the experimental conditions, it can assume different patterns of intracellular distribution in vitro (punctate vs filamentous), depending on culture conditions and the presence of estrogens.

The authors investigated the state of immunity, before and after surgery, in a group of 6 methisoprinol-treated patients and in a 10-patient control group both affected by malignant neoplasia. All the patients exhibited various degrees of immuno-depression. Versus the control group the group treated with 1-g methisoprinol injections at the dosage of 4 g daily for 7 days after surgery showed a positive effect on post-surgical immuno-depression.

Myosin heavy chain (MHC) composition of chemically-induced rhabdomyosarcoma (RMS) was analyzed by gel electrophoresis and Western blotting using a panel of monoclonal antimyosin antibodies specific for embryonic-, neonatal-, slow- and adult fast-type MHC isoforms. Myosin extracted from tumours and electrophoresed on 6%-sodium dodecyl sulfate (SDS)glycerol gels was found to migrate as three distinct MHC components. These polypeptides were present in different relative amounts in the five RMS studied. Western blotting experiments revealed that variable proportions of embryonic-, slow- and adult fast-, but not neonatal-type, MHC isoforms are consistently expressed in RMS. Indirect and double immunofluorescence procedures applied to cryosections of tumoral tissue showed that: (a) RMS cells were unreactive with antineonatal-type-MHC antibody, (b) the majority of neoplastic, desmin-positive, cells contained embryonic- as well as adult fast-type MHCs and (c) a minority of cells were labelled by anti-slow MHC antibody. The results of this study indicate that there is no obligatory sequence of MHC isoform expression in the molecular transition (emb----neo----adult) which occurs during rat skeletal myogenesis.