Efficacy of peptide bound m-l-sarcolysin (peptichemio) on melphalan resistant human myeloma cellsIn vitro

Peptichemio (PTC) is a mixture of six synthetic oligopeptides, each containing the alkylating agent m-di(2-chloroethyl) amino-phenylalanine. Freshly obtained myeloma cell infiltrated human bone marrow specimens were in parallel exposed to melphalan and PTC. The cytotoxic effect of the drugs on the myeloma cells of each specimen was measured by the differential staining culture method (DISC). PTC displayed higher cytotoxicity to the myeloma cells as compared to melphalan in all 12 cases analysed. The increase of the cytotoxic effect of PTC compared to melphalan varied between different cases. In melphalan resistant cases the cytotoxic effect of PTC as compared to melphalan was clearly significant(P = 0.001).     

Amphiregulin anti-sense oligodeoxynucleotides inhibit growth and transformation of a human colon carcinoma cell line

Amphiregulin (AR) is a secreted heparin-binding growth factor that is structurally and functionally related to epidermal growth factor (EGF) and transforming growth factor a (TGFα). GEO cells are from a human colon cancer cell line that expresses high levels of AR protein and mRNA. To assess the role of AR in colon-cancer cell proliferation and transformation, 2 different anti-sense 20-mer phosphorothioate oligodeoxy-nucleotides (AR AS-1 and AR AS-2 S-oligos) complementary to the 5′ sequence of AR mRNA were synthesized. Both AR AS S-oligos were able to inhibit the anchorage-dependent growth (ADG) of GEO cells. The 2 AR AS S-oligos were equipotent when used in equimolar concentrations. In particular, a 40% growth inhibition was observed at a concentration of 10 μM, while a mis-sense S-oligo used as control had no effect on GEO cell growth. The AR AS-1 S-oligo used at the same concentration also inhibited by 40% the ³H-thymidine incorporation by DNA of GEO cells. The anchorage-independent growth (AIG) of GEO cells was even more significantly affected by AR AS S-oligo treatment. In fact, up to 80% inhibition of the AIG of GEO cells was observed when cells were treated with 10 μM of both AR AS S-oligos. Finally, the AR AS S-oligos were able to specifically inhibit AR protein expression in GEO cells, as assessed by immunocytochemistry. These data suggest that AR is involved in colon-cancer cell transformation, and that AR may represent a suitable target for gene therapy in human colon carcinomas. © 1995 Wiley-Liss, Inc.     

Olivofloccular circuit in oculomotor control: binocular optokinetic stimulation

 The metabolic activation of the olivocerebellar pathway during binocular optokinetic stimulation was studied in the guinea pig, by means of the semiquantitative ¹⁴C-2-deoxyglucose (2DG) technique. The experimental group underwent binocular horizontal stimulation, whereas the control animals were either kept in the dark or allowed to view a stationary pattern. The local metabolic activity index in the dorsal cap of the inferior olive was higher on the side contralateral to the eye that had been stimulated in the temporonasal (T-N) direction in the horizontal group; in contrast, the floccular region showed higher activity on the side ipsilateral to the T-N-stimulated eye. These findings support the involvement of the olivocerebellar pathway in the horizontal optokinetic response. A phylogenetic hypothesis is suggested to explain inconsistent results found in the literature. Received: 25 March 1998 / Accepted: 7 December 1998     

Diffuse gastrointestinal dysmotility by ultrasonography, manometry and breath tests in colonic inertia

Patients with colonic inertia, the most severe form of chronic functional constipation, may present with a more diffuse panenteric motility disorder. We describe a case of a woman with severe longstanding colonic inertia associated with chronic functional dyspepsia and defective gastric, gallbladder and small intestinal motility, as confirmed by several diagnostic tests including two breath tests with the 13C-stable isotope. A subclinical form of authonomic sympathetic neuropathy was diagnosed, providing a possible pathophysiological explanation for the presence of simultaneous multiple motility defects of the gastrointestinal tract.     

Body Composition Changes in Gastric Cancer Patients during Preoperative FLOT Therapy: Preliminary Results of an Italian Cohort Study

Background: The impact of the new chemotherapy, fluorouracil plus leucovorin, oxaliplatin, and docetaxel (FLOT) on body composition in gastric cancer (GC) patients remains unknown. We assessed body composition changes of GC patients receiving the FLOT regimen and their impact on treatment outcomes. Methods: Preoperative pre- and post-FLOT computed tomography (CT) scans of advanced GC patients were studied. Lumbar skeletal muscle index (SMI) and adipose indices were calculated before and after FLOT. Results: A total of 26 patients were identified between April 2019 and January 2020. Nineteen patients were sarcopenic at diagnosis. The mean BMI decreased (from 24.4 ± 3.7 to 22.6 ± 3.1; p < 0.0001) as well as the SMI (from 48.74 ± 9.76 to 46.52 ± 9.98; p = 0.009) and visceral adipose index (VAI) (from 49.04 ± 31.06 to 41.99 ± 23.91; p = 0.004) during preoperative FLOT therapy. BMI, SMI, and VAI variations were not associated with toxicity, Response Evaluation Criteria in Solid Tumors (RECIST), response, delay and completion of perioperative FLOT chemotherapy, and the execution of gastrectomy; a decrease of SMI ≥ 5% was associated with a higher Mandard tumor regression grade (p = 0.01). Conclusions: Almost three-quarters (73.1%) of GC patients were sarcopenic at diagnosis. Preoperative FLOT was associated with a further reduction in SMI, BMI, and VAI. These changes were not associated with short-term outcomes.     

A pediatric disease to keep in mind: diagnostic tools and management of bronchiectasis in pediatric age

Bronchiectasis in pediatric age is a heterogeneous disease associated with significant morbidity.The most common medical conditions leading to bronchial damage are previous pneumonia and recurrent lower airway infections followed by underlying diseases such as immune-deficiencies, congenital airway defects, recurrent aspirations and mucociliary clearance disorders.The most frequent symptom is chronic wet cough. The introduction of high-resolution computed tomography (HRCT) has improved the time of diagnosis allowing earlier treatment.However, the term “bronchiectasis” in pediatric age should be used with caution, since some lesions highlighted with HRCT may improve or regress. The use of chest magnetic resonance imaging (MRI) as a radiation-free technique for the assessment and follow-up of lung abnormalities in non-Cystic Fibrosis chronic lung disease is promising.Non-Cystic Fibrosis Bronchiectasis management needs a multi-disciplinary team. Antibiotics and airway clearance techniques (ACT) represent the pillars of treatment even though guidelines in children are lacking. The Azithromycin thanks to its antinflammatory and direct antimicrobial effect could be a new strategy to prevent exacerbations.