BRAF and PIK3CA genes are somatically mutated in hepatocellular carcinoma among patients from South Italy.

Poor data have been previously reported about the mutation rates in K-RAS, BRAF, and PIK3CA genes among patients with hepatocellular carcinoma (HCC). Here we further elucidated the role of these genes in pathogenesis of primary hepatic malignancies. Archival tumour tissue from 65 HCC patients originating from South Italy were screened for mutations in these candidate genes by direct sequencing. Overall, oncogenic mutations were detected in 15 (23%) patients for BRAF gene, 18 (28%) for PIK3CA gene, and 1 (2%) for K-RAS gene. Using statistical analysis, BRAF mutations were significantly correlated with the presence of either multiple HCC nodules (P=0.021) or higher proliferation rates (P=0.034). Although further extensive screenings are awaited in HCC patients among different populations, our findings clearly indicated that mutational activation of both BRAF and PIK3CA genes does contribute to hepatocellular tumorigenesis at somatic level in Southern Italian population.

Metachronous Paget's disease of the breast: case report.

Paget breast disease is a kind of intraductal carcinoma that through an intracanalicular diffusion invades the basal epidermal layer, reaching the areola and nipple, producing a typical erythematous desquamative eczematous-like lesion. This neoplasia can remain undetected for a long time and inadequately treated as a dermatological affection. Synchronous or metachronous lesions are very uncommon. Surgical choice is conditioned by the presence of a tumor below the epidermal lesion, by its dimensions, and by the possible lymph node involvement. Surgical therapy can be radical or conservative. From our experience we think that lesion biopsy is always necessary to formulate a correct diagnosis and to schedule an appropriate therapeutic approach. In our case, a biopsy was performed first, then on the basis of the frozen section analysis a radical mastectomy with axillary third level lymph nodes dissection, because of the large dimensions of the lesion and the previous history of a methachronous lesion.

[Conservative anal fistula treatment with collagenic plug and human fibrin sealant. Preliminary results]. / Trattamento conservativo delle fistole perianali con plug in matrice extracellulare biologica e colla di fibrina umana: esperienza preliminare.

The authors, on the basis of a long clinical experience with human fibrin glue in general surgery, compared two different extracellular matrix (collagen), Surgisis and TissueDura, with human fibrin glue, applied during the operation, and sometimes in postoperative, to obtain the healing of perianal fistulas. The collagenic extracellular matrix provides, according to the rationale suggested, an optimal three-dimensional structure for the fibroblastic implant and neoangiogenesis, hence for the fistula "fibrotizzation" and closure. The encouraging results for transphincteric fistulas and a simple and easy technique push to researchers on samples statistically significant.

[Hormonal therapy in oncologic treatment: pathogenic hypotheses and interactions between thyroid and breast pathologies]. / La terapia ormonale nel trattamento oncologico: ipotesi patogenetiche e interazioni tra patologia tiroidea e mammaria.

INTRODUCTION: The aim to individuate the eventual correlation between the two pathologies has justified deeper studies to achieve new prospective approaches for both disease. BACKGROUND: We have selected 4 groups of patients who presented an association between the two pathologies: a) malignant breast pathology associated to a malignant thyroid pathology, b) patients with breast carcinoma who presented association with some thyroid alterations, c) patients with thyroid carcinoma who presented association with some breast alterations, d) patients who presented some associations between benign breast pathology and benign thyroid pathology. MATERIALS AND METHODS: We have excluded all patients with a clear physiological or surgical menopausal status, and we've so considered only patients with a regular menstrual cycle. We've so selected a group of 120 patients and we've performed in all these patients during the early follicular phase the following exams: breast echographic evaluation and thyroid echographic-structure and volume determination and finally hormonal determinations we have so obtained two breast subgroups: 32 patients with hyperestrogenic integrative hormonal characteristics, 28 patients subjected to adjuvant hormonal therapy with hypoestregenic hormonal status and finally two thyroid subgroups, 22 patients showing clinical or subclinical hypothyroidism, 38 patients showing clinical or subclinical hyperthyroidism. We've compared these data to a random age-matched health control women group of 25 patients. RESULTS: The first group of patient showed a thyroid hormonal pattern of subclinical hypothyroidism or at least free T3 and free T4 mean value currently under and TSH and TPO Ab levels curve currently over the mean values of the control group. The second group showed the TSH suppressed with free T3 and free T4 curves currently over the mean value of the control group. The third group showed slight elevations in serum PRL levels curve. The fourth group showed increased estrogen levels-curve, often over the mean value of the control group. CONCLUSION: How much is it allowed to perform an hormonal therapy, specially for a benign pathology if we're not yet able to understand the deep and unknown interaction between breast and thyroid?

Cellulose-based hydrogels as body water retainers.

In this work the possibility of using hydrogels as body water retainers for a therapeutic aid in pathologies such as oedemas of various origins was explored. For such a purpose, the material requires a good compatibility and a controlled swelling capacity without altering the body electrolyte homeostasis. The hydrogel was designed to meet the swelling requirements with the physiological constraints and its biocompatibility was assessed either in vitro or in vivo. Absorption tests were performed in order to define the swelling behavior by varying the pH and ion content of the external solution. The hydrogel swelling capacity was assessed in the presence of various solvents, in order to evaluate its absorption capacity in solutions similar to biological fluids. In addition, the capacity of the gel to modify electrolyte homeostasis by adsorbing ions such as calcium, potassium and sodium was tested. In order to assess the gel biocompatibility after contact of the hydrogel with intestinal cells, arachidonic acid relase was determined. No significant intracellular increase of free arachidonic acid was found in the cells after up to 2 h of contact with the gel. The results suggest that, as far as brief periods are concerned, the gel does not cause an inflammatory response in intestinal cells.

Truncal vagotomy, antrectomy and Roux-en-Y gastrojejunostomy in the treatment of duodenogastric reflux disease.

BACKGROUND/AIMS: The surgical treatment of duodenogastric reflux (DGR), resistant to medical therapy, in patients with intact stomach is difficult to standardize. The aim of this study is to present our experience on 5 patients, all cholecystectomized, with severe DGR disease treated surgically. METHODS: Out of a group of 223 patients suffering from nonulcerous dispeptic pathology presenting to our department, we selected 5 patients suffering from alkaline reflux gastritis in intact stomach. The diagnosis of primary DGR was made using Wilson's criteria. The surgical procedure adopted consisted of a truncal vagotomy, antrectomy, and a Roux-en-Y gastrojejunostomy. RESULTS: No perioperative mortality was observed. Twelve months after surgery all patients expressed satisfaction with the result of the operation and complained of no severe disturbances. A sense of postprandial fullness with a sense of pain in the left shoulder persisted in one case only, requiring the consumption of small and frequent meals. Radiological examination of the upper gastrointestinal tract of these patients showed notably delayed emptying of the gastric stump, while the endoscopic picture was completely normal. CONCLUSION: The antrectomy and Roux-en-Y gastrojejunostomy is a better known operation, easily executed, and has the advantage that it can be performed on patients previously operated on for gastric resection and therefore suffering from secondary reflux. It also has the advantage of removing the gastric antrum where mucous atrophy is more frequent and is susceptible to neoplastic degeneration. However, at the present time the choice between different types of operation depends exclusively on the personal conviction and experience of the surgeon.

The Hohn catheter in the management of haemopoietic stem cell transplant recipients.

Patients undergoing bone marrow transplantation require a reliable venous access. The authors have tested the feasibility and safety of a new, silicone, open-ended, non-tunnelled central venous catheter (CVC), the Hohn catheter (Bard Access System, USA). From January 1994 to December 1996, 58 Hohn were inserted into 56 bone marrow transplant (BMT) patients (26 women: 30 men; mean age 38 years, range 19-62 years). The CVC was inserted percutaneously at the bedside by puncture of the subclavian or the internal jugular vein. No early complications were observed. Significant late complications were infection (documented only in 14%) and accidental removal (11%). The median life of the CVC was 30 days (range 15-180 days). Major causes of removal were end of use (25 patients) and fever (19 patients; but infection was documented only in eight patients). In spite of the relatively small gauge (5 Fr), the Hohn catheter was adequate for rapid or high density infusion. In our experience, the unique features of the Hohn CVC (versatility, optimal biocompatibility, bedside management, low cost) may contribute to making the BMT procedure safer and less expensive.

Tamoxifen aziridine, a novel affinity probe for P-glycoprotein in multidrug resistant cells.

In this study for the first time we used an electrophilic analog of tamoxifen, [3H]tamoxifen aziridine, and demonstrated that it covalently and specifically binds to P-glycoprotein in multidrug resistant cells. Tamoxifen and its metabolites, N-desmethyltamoxifen and 4-hydroxytamoxifen, were potent inhibitors of [3H]tamoxifen aziridine binding to P-glycoprotein with 4-hydroxytamoxifen > tamoxifen > N-desmethyltamoxifen. The multidrug resistance-related drugs inhibited [3H]tamoxifen aziridine binding with vinblastine > vincristine > doxorubicin > actinomycin D, while colchicine enhanced the binding. Moreover, the multidrug resistance modulators verapamil, nicardipine, diltiazem, prenylamine, cyclosporin A, FK506, dibucaine, reserpine, monensin and progesterone were all potent inhibitors of [3H]tamoxifen aziridine binding to P-glycoprotein. Our data provide the first evidence that [3H]tamoxifen aziridine directly binds to P-glycoprotein and interacts with the binding sites for multidrug resistance-related drugs and modulators.

[Nonpalpable lesions of the breast. Diagnostic and therapeutic considerations]. / Lesioni non palpabili della mammella. Considerazioni diagnostiche e terapeutiche.

The early detection of breast cancer is of primary importance, as one method which many reduce the unacceptably high mortality rate associated with this disease. In fact, it is well stated that the most concrete possibility of therapeutic success in the treatment of breast cancer is represented by early treatment, while the disease is still localized. Then a screening program is necessary in asymptomatic women, to diagnose the disease as early as possible even in case of non palpable lesion. Mammography is nowadays the most specific and sensitive investigation for clinically occult breast cancer. In this study we searched for mammographic findings with the best predictive value for cancer and we tested the most careful techniques for preoperative localization and surgical biopsy of nonpalpable breast lesions. Seventy-one asymptomatic women (age range: 31-76 years, mean: 53.6) underwent stereotaxic needle localization to perform surgical biopsy of mammographically suspicious but nonpalpable breast lesions. Mammographic findings were classified as: a) well defined and smooth bordered opacities (11.3% of cases); b) poorly defined, irregular, spiculated and stellate opacities (32.4% of cases); c) lowly suspicious microcalcifications, larger, rounder, fewer in number (19.7% of cases); d) highly suspicious microcalcifications, with irregularities on shape, density and size described as clustered and polymorphic (36.6% of cases). Cancer was found in 22 cases (31%); 12 of those (54.5%) were associated with highly suspicious microcalcifications, 10 of those (45.5%) were associated with stellate and poorly defined opacities.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical and mycological evaluation of fluconazole in the secondary prophylaxis of esophageal candidiasis in AIDS patients. An open, multicenter study.

A prospective, multicenter, open study of fluconazole prophylaxis was performed in AIDS patients to evaluate the efficacy and toxicity of the drug in preventing relapses of esophageal candidiasis. To this aim, 99 AIDS patients who presented a first episode of clinically and microbiologically confirmed esophageal candidiasis were enrolled in eleven clinical centers scattered throughout the Italian territory. After resolution of this initial esophagitis, all subjects were given fluconazole, 100 mg/die, and followed up for a 6 month period. Only 7 out of the 99 patients enrolled had a relapse of Candida esophagitis, during a mean follow-up period of 138.5 days. All relapsing patients had CD4+ cell number < 100/microliters at baseline. Mild side effects were reported in only eight patients. However, 14 of the 27 subjects from whom serial serum samples were available became (12) or remained (2) antigenemic during fluconazole prophylaxis, independently from relapse, suggesting the persistence of tissue-invasive, proliferating Candida cells. Overall, the data of this study suggest a beneficial effect of prophylactic maintenance therapy with fluconazole against Candida esophagitis, particularly in the population with > 100 CD4+/microliters. However, the data on Candida antigenemia in these patients invite the consideration of a relative inefficiency of the drug to eradicate the microrganism from the esophageal tissue.

Long-term follow-up of zidovudine therapy in asymptomatic HIV infection: results of a multicenter cohort study. The Italian Zidovudine Evaluation Group.

In 1990 the results of a placebo-controlled study conducted within the AIDS Clinical Trials Group (ACTG 019) showed that in the short term, zidovudine was effective in slowing progression to advanced disease in HIV-infected asymptomatic patients with low CD4 cell counts. More recently, the preliminary results of the Concorde Trial suggested that while the data at 1 year agreed with those of ACTG 019, no sustained clinical benefit was detectable at 3 years for early versus deferred therapy. Therefore, the length of the clinical usefulness of zidovudine in this population is still to be determined. We evaluated the 2-year outcome of zidovudine therapy in asymptomatic patients through the prospective follow-up of a cohort of 936 subjects with low CD4+ (< 500/mm3) counts who strictly satisfied, at enrollment, the inclusion and exclusion criteria of the ACTG 019 trial. The clinical end point of the analysis was the development of AIDS. The majority (72.2%) of the individuals in the cohort acquired HIV infection through intravenous drug use; 26.6% were women. The median baseline CD4 cell count was 308/mm3. At 55 weeks of mean follow-up, the progression rate to AIDS (3.2 events per hundred person-years) appears to be comparable to that already reported at the same mean follow-up time for the ACTG 019 zidovudine-treated asymptomatic patients. After 124 weeks of mean follow-up, the overall rate of progression to AIDS was 5.2 per hundred person-years.(ABSTRACT TRUNCATED AT 250 WORDS)

N-(p-azido-3-[125I]iodophenethyl)spiperone binds to specific regions of P-glycoprotein and another multidrug binding protein, spiperophilin, in human neuroblastoma cells.

P-glycoprotein (P-gp) is an energy-dependent drug extrusion pump with broad specificity for diverse hydrophobic anticancer agents and compounds known to reverse multidrug resistance (MDR). Among MDR reversing agents, phenothiazines (PTZs) and related compounds may sensitize MDR by interacting with a specific binding site(s) on P-gp and by other mechanisms. In order (1) to identify a binding site for PTZs and related compounds on P-gp, (2) to examine whether these compounds and other MDR modulators bind to the same domains of P-gp, and (3) to identify proteins with high specificity for these neuroleptic agents and other MDR modulators, we used a butyrophenone D2-dopamine receptor photoaffinity probe, N-(p-azido-3-[125I]iodophenethyl)spiperone ([125I]NAPS). [125I]NAPS was actively effluxed from vincristine (VCR)-resistant SH-SY5Y/VCR human neuroblastoma cells, and nonradioactive I-NAPS was a potent chemosensitizing agent. After photolabeling, the probe bound specifically and with high efficiency to P-gp and to another multidrug binding 17-kDa membrane-bound protein, spiperophilin, in these cells. The efficiency of [125I]NAPS binding to P-gp was 5-6-fold more than [3H]azidopine and [125I]arylazidoprazosin ([125I]AAP), known photoaffinity analogs for P-gp. [125I]NAPS photolabeling of P-gp was preferentially competed by MDR-related drugs, with vinblastine > VCR > colchicine > doxorubicin > actinomycin D. Many drugs that are known to reverse MDR were potent inhibitors of [125I]NAPS binding to P-gp. While PTZs and related compounds were potent inhibitors of [125I]NAPS binding to P-gp, most of them enhanced the binding of [125I]AAP significantly. cis-Flupentixol increased the binding of [125I]AAP to P-gp 9-fold more than did trans-flupentixol, but both were potent inhibitors of [125I]NAPS binding, suggesting their stereoselective effect on the [125I]AAP binding site. Proteolysis of [125I]NAPS-bound P-gp with Staphylococcus aureus V8 protease revealed that this probe binds to two major peptides, 6 and 8 kDa, and a number of minor ones, while [125I]AAP binds to only an 8-kDa peptide. These results suggest that modulators of MDR may interact with separate or overlapping domains. Furthermore, most MDR modulators, dopaminergic drugs, and beta-adrenergic antagonists used also inhibited binding of [125I]-NAPS to spiperophilin, suggesting that this protein may be a target for these drugs.

Anti-cardiolipin antibodies in HIV infection are true antiphospholipids not associated with antiphospholipid syndrome.

The aim of the present study was to evaluate the fine specificity of anticardiolipin (aCL) antibodies detectable in the sera of patients with HIV infection. aCL are generally associated with thrombotic events in autoimmune diseases. A solid phase ELISA which discriminates between aCL binding to phospholipids and aCL binding to phospholipid/beta 2-glycoprotein I (cofactor) complex was employed. Thirty-nine HIV and 20 aCL positive systemic lupus erythematosus (SLE) sera were examined. In HIV sera, reduced binding to phospholipid was seen if cofactor was added. On the contrary, in SLE-sera the cofactor improved aCL binding. No thrombotic events were recorded in HIV infected subjects presenting with aCL. Thus, aCL in HIV infection and in SLE appear to have different specificities. In HIV infection the true epitope of aCL is likely to be on the phospholipid component only, whereas in SLE aCL seem directed against the cofactor/CL complex. Considering the anticoagulant role of beta 2-glycoprotein I, this observation might account for the lack of thrombosis in HIV patients with "true" aCL.

Functional analysis of P-glycoprotein mutants identifies predicted transmembrane domain 11 as a putative drug binding site.

The substitution of a single serine to phenylalanine residue within the predicted transmembrane domain 11 of P-glycoproteins (P-gps) encoded by mouse mdr1 (Ser941, 1S;Phe941, 1F) or mdr3 (Ser939, 3S; Phe939, 3F) strongly modulates both the overall activity and substrate specificity of the two P-gps. In cell clones expressing either wild-type (1S, 3S) or mutant P-gps (1F, 3F), we show that the modulating effect of the mutation on the levels of adriamycin (ADM) resistance detected in drug cytotoxicity assays is paralleled by a similar modulation of the intracellular accumulation and extracellular efflux of radiolabeled adriamycin ([14C]ADM) from preloaded cells. Cytofluorescence studies with ADM on live cells produce similar results and demonstrate strong nuclear ADM accumulation only in drug-sensitive LR cells and in the 1F expressing cells, with little if any accumulation in 1S, 3S, or 3F expressing cells. Drug cytotoxicity and drug transport assays carried out in the presence of verapamil or progesterone suggest that the Ser to Phe substitution also reduces the capacity of these two reversal agents to modulate P-gp activity. Labeling experiments with the photoactivatable P-gp ligands iodoarylazidoprazosin and azidopine indicate a strong reduction in binding of these photoactivatable probes to the mutant P-gps (1F, 3F) as compared to their wild-type counterparts (1S,3S). These results indicate that the studied mutations in TM11 reduce drug transport by decreasing initial drug binding to P-gp. This phenotype is opposite to that of a mutation near TM3 in human MDR1 (pst 185), where decreased drug transport is associated with increased drug binding and decreased drug release from P-gp [Safa, A. R., Stern, R. K., Choi, K., Agresti, M., Tamai, I., Metha, N. D., & Roninson, I. B. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 7225-7229].

Liposome-mediated modulation of multidrug resistance in human HL-60 leukemia cells.

BACKGROUND: Multidrug resistance (MDR) is a major obstacle in cancer treatment. Resistance of cultured tumor cells to major classes of cytotoxic drugs is frequently due to expression of a plasma membrane P-glycoprotein encoded by MDR genes. We have demonstrated that liposome-encapsulated doxorubicin is more toxic than the free drug and that it modulates MDR in Chinese hamster LZ cells and human colon cancer cells. PURPOSE: To investigate further the association between expression of P-glycoprotein and modulation of MDR by liposome-encapsulated doxorubicin, we studied vincristine-resistant HL-60/VCR leukemia cells, which express P-glycoprotein, and doxorubicin-resistant HL-60/ADR leukemia cells, which do not. METHODS: Cells were exposed to various concentrations of free doxorubicin and liposome-encapsulated doxorubicin. The cellular content of doxorubicin was determined by fluorescence analysis, and cytotoxicity was determined by cell growth inhibition. Photoaffinity-labeling studies of P-glycoprotein binding were performed on HL-60/VCR and HL-60/ADR cells and KB-GSV2 cells transfected with the MDR1 gene (also known as PGY1). RESULTS: The concentrations that caused 50% inhibition of growth (IC50) for free doxorubicin in HL-60, HL-60/ADR, and HL-60/VCR cells were 30 nM, 9 microM, and 0.9 microM, respectively. The values for liposome-encapsulated doxorubicin in parental HL-60 cells and HL-60/ADR cells were 20 nM and 9 microM, respectively, indicating little or no sensitization. In contrast, HL-60/VCR cells were fivefold more sensitive to liposome-encapsulated doxorubicin than to free doxorubicin, and IC50 was reduced to 0.17 microM. In HL-60 cells exposed to liposome-encapsulated doxorubicin, intracellular doxorubicin accumulation was less than that seen with free drug. In contrast, in HL-60/VCR cells, accumulation was twofold to threefold higher than that with free doxorubicin. Liposome-encapsulated doxorubicin completely inhibited the photoaffinity labeling of P-glycoprotein by azidopine in membrane vesicles of HL-60/VCR cells, with a potency comparable to that of azidopine, suggesting that circumvention of MDR by liposomes is related to their specific interaction with P-glycoprotein. The studies with KB-GSV2 cells indicated that blank liposomes can directly inhibit photoaffinity labeling of P-glycoprotein. CONCLUSIONS: These results demonstrate the effectiveness of liposome-encapsulated doxorubicin in overcoming resistance in the multidrug-resistant phenotype of HL-60/VCR cells by direct interaction with P-glycoprotein. Furthermore, they indicate that liposome-encapsulated doxorubicin may be an effective treatment for human cancers.

[Preoperative radiotherapy in locally advanced rectal cancer: risks and complications?]. / La radioterapia preoperatoria nel cancro rettale localmente avanzato: rischi e complicanze?

Adjuvant radiotherapy in advanced rectal cancer is currently considered of interest: preoperative radiotherapy in particular seems to provide better results. However, doubts in its use arise from fear of technical difficulties at surgery and increase of complications. In Authors' opinion, though, preoperative radiotherapy associated with perineal omentoplasty represents a real progress in the management of rectal cancer. Preliminary experience supports this feeling.

Survival of zidovudine-treated patients with AIDS compared with that of contemporary untreated patients. Italian Zidovudine Evaluation Group.

OBJECTIVE: To assess the long-term effectiveness of zidovudine (AZT) in patients with acquired immunodeficiency syndrome (AIDS). This assessment has never been adequately done because controlled clinical trials were stopped early and survival comparisons were made with historical controls. DESIGN: Nonrandomized contemporary observational study of patients treated and not treated with zidovudine. SETTING: Twenty-three AIDS treatment centers throughout Italy that reported cases to the National Registry of AIDS Cases between July 1987 and March 1988. PATIENTS: One hundred fifty-nine zidovudine-treated and 112 untreated patients with AIDS, the majority of whom had acquired human immunodeficiency virus (HIV) infection through intravenous drug use. OUTCOME MEASURES: Median survival and 1- and 2-year survival for treated and untreated groups, as estimated using the Kaplan-Meier method. Cox proportional hazards regression analysis was also used to identify independent predictors of survival among the variables studied. RESULTS: Patients were similar with respect to CD4/CD8 ratio, age, sex, clinical and immunological status at diagnosis, and source of HIV infection. After 24 months, survival was 45.9% (95% confidence interval [CI], 36.1% to 55.7%) in the treated group and 20.5% (95% CI, 12.6% to 28.3%) in the untreated group, with median survival of 21.2 and 9.6 months, respectively. CONCLUSIONS: Possible biases of this study include imperfect matching for clinical status and better overall medical care of treated patients. Nevertheless, we believe that the observed differences in survival were primarily due to zidovudine treatment.

Megestrol acetate reverses multidrug resistance and interacts with P-glycoprotein.

We evaluated the multidrug resistance (MDR)-modulating effects of progesterone (PRG) and an orally active, structurally related compound, megestrol acetate (MA), in several MDR human cell lines. At 100 microM, both steroids inhibited the binding of a Vinca alkaloid photoaffinity analog to P-glycoprotein (P-gp) in MDR human neuroblastic SH-SY5Y/VCR cells [which show greater than 1500-fold resistance to vincristine (VCR) in the tetrazolium dye (MTT) assay]. However, 100 microM MA markedly enhanced the binding of [3H]-azidopine to P-gp in both SH-SY5Y/VCR cells and the MDR human epidermoid KB-GSV2 cell line (which displays 250-fold resistance to VCR in the MTT assay). PRG had little effect on the binding of [3H]-azidopine to P-gp. MA at low doses was more effective than PRG in sensitizing cells to VCR and enhancing their accumulation of [3H]-VCR. The highly resistant SH-SY5Y/VCR subline exhibited significant collateral sensitivity to both steroids. These data suggest that MA may be a clinically useful modulator of MDR.

[Carcinoma of the cervical esophagus. Problems of surgical technique]. / Carcinoma dell'esofago cervicale. Problemi di technica chirurgica.

The tape shows the surgical technique used by the Authors for the alimentary tract reconstruction after total esophagectomy for cancer of the upper esophagus. A review of the main reconstructive techniques used for this disease is reported.