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Objectives: A number of previous studies has provided evidence that the well-known anti-bacterial quinolones may have potential as anti-cancer drugs. The aim of this study was to evaluate potential anti-tumour activity and selectivity of a set of 6-aminoquinolones showing some chemical similarity to naphthyridone derivative CX-5461, recently described as innovative anti-cancer agent. Materials and methods: In-house quinolones 1-8 and ad hoc synthesized derivatives 9-13 were tested on Michigan Cancer Foundation-7 (MCF-7) breast cancer cells and mesenchymal progenitor (MePR2B) cell lines, analysing their effects on the cell cycle and cell death using FACS methodology. Activation of p53 was evaluated by western blotting. Results: Benzyl esters 4, 5 and their amide counterparts 12, 13 drastically modulated MCF-7 cell cycles inducing DNA fragmentation and cell death, thus proving to be potential anti-tumour compounds. When assayed in non-tumour MePR2B cells, compounds 4 and 5 were cytotoxic while 12 and 13 had a certain degree of selectivity, with compound 12 emerging as the most promising. Western blot analysis revealed that severe p53-K382ac activation was promoted by benzylester 5. In contrast, amide 12 exerted only a moderate effect which was, however, comparable to that of suberoylanilide hydoxamic acid (SAHA). Conclusions: Taken together, these results further reinforce evidence that quinolones have potential as anti-cancer agents. Future work will be focused on understanding compound 12 mechanisms of action, and to obtain more potent and selective compounds. [ABSTRACT FROM AUTHOR]

Hypopharyngeal and cervical esophageal tumors represent 5–10% of all esophageal neoplasms and are challenging for both surgeons and oncologists, because the choice of the adequate therapeutic strategy is not clearly defined and therefore difficult. In fact, although surgical treatment represents the gold standard of therapy, chemo-radiotherapy, previously used as adjuvant treatment, has been more recently adopted with curative intent, leaving to surgery a salvage role only. When surgery is required it is advisable to reduce patients’ trauma. The present study reports on a personal technique for minimally invasive pharyngo-laryngo-esophagectomy and reconstruction with the whole stomach. We use a laparoscopic approach for mobilization of the stomach, transhiatal esophageal dissection and to follow transhiatal gastric transposition to the neck combined to a cervicotomy to perform pharyngo-laryngectomy, proximal esophageal mobilization, and pharyngo-gastric anastomosis. We performed this technique on four patients with recurrent disease after initially curative primary chemo-radiotherapy. Mean operative time was 345 min (range: 300–384). There were no intraoperative complications. All patients were extubated immediately after the operation and were managed in postoperative care unit for a mean time of 10 days (range: 7–12). Enteral nutrition was begun on post-operative day (POD) 1. The nasogastric tube and drainages were removed on POD 11, and patients immediately started oral nutrition. One patient had a TIA (transient ischemic attack) on POD 2. All patients were discharged within 20 days (18–20). Initial experience with this minimally invasive technique in selected patients is encouraging because it seems to minimize postoperative complications and allows early rehabilitation. [ABSTRACT FROM AUTHOR]

Background: Proper construction of an effective fundoplication to control reflux depends on accurate identification of the gastroesophageal junction (GEJ). In laparoscopic surgery, the accuracy of this GEJ determination is unknown. Methods: In 40 consecutive laparoscopic antireflux procedures, the GEJ location was determined independently by endoscopy and laparoscopy, and the differences were measured. After this was completed, endoscopic examination of the fundoplication was performed. Results: The "laparoscopic" GEJ was identified within 1 cm of the "endoscopic" GEJ in 36 of 40 (90%) patients. In four patients, this difference was greater and the GEJ always higher than determined by laparoscopy. These patients had greater acid exposure and esophageal injury. On two occasions, the fundoplication was reconstructed on the basis of endoscopic findings. Conclusions: With laparoscopy, the surgeon can accurately determine the GEJ location in most patients. In approximately 10%, the GEJ is actually higher than the surgeon believes, and the fundoplication may be created lower than intended. Intraoperative endoscopy helps to identify the GEJ location and evaluate the wrap once completed. [ABSTRACT FROM AUTHOR]

Interest in the inhibitors of type-B monoamine oxidase has grown in recent years, due to the evidence for multiple roles of one such agent (selegiline) in the pharmacological management of neurodegenerative disorders. A set of 130 reversible and selective inhibitors of MAO-B (including tetrazole, oxadiazolone, and oxadiazinone derivatives) were taken from the literature and subjected to a three-dimensional quantitative structure–activity relationship (3D-QSAR) study, using CoMFA and GOLPE procedures. The steric and lipophilic fields, alone and in combination, provided us with informative models and satisfactory predictions (q2=0.73). The validity of these models was checked against the 3D X-ray structure of human MAO-B. Flexible docking calculations, performed by using a new approach which took advantage from QXP and GRID computational tools, showed the diverse inhibitors to interact with MAO-B in a similar binding mode, irrespective of the heterocycle characterizing them. A significant trend of correlation was observed between estimated energies of the complexes and the experimental inhibition data. [ABSTRACT FROM AUTHOR]

BACKGROUND: Since its first description in the early 1990s, minimally invasive Heller myotomy has become the treatment of choice for esophageal achalasia. We report the experience of a single unit with thoracoscopic Heller myotomy (THM) and laparoscopic Heller myotomy (LHM) and we analyze the short- and long-term surgical outcomes in patients treated by each of the two approaches. METHODS: We evaluated retrospectively 33 patients who underwent surgical treatment for achalasia. Sixteen patients underwent THM without an antireflux procedure, and 17 patients underwent LHM and partial anterior fundoplication (n = 10) or closure of the angle of His (n = 7). RESULTS: Mean operative time was significantly shorter for LHM than for THM (150 vs 222 min, respectively) (p = 0.0001). Mean hospital stay was significantly shorter after LHM than after THM (2.0 ± 1.0 vs 5.1 ± 2.2 days, respectively) (p = 0.0001). Six of 16 patients (37.5%) in the THM group experienced persistent or recurrent dysphagia compared to one of 17 patients (5.8%) in the LHM group (p = 0.04). Heartburn developed in five patients (31.2%) after THM and in one patient (5.8%) after LHM (p = 0.07). Regurgitation developed in four patients (25%) after THM and in one patient (5.8%) after LHM (p = 0.149). Lower esophageal sphincter (LES) basal pressure decreased significantly from 30.1 ± 5.07 to 15.3 ± 2.1 after THM and from 32.1 ± 5.9 to 10.5 ± 1.7 after LHM (p = 0.0001). Mean esophageal diameter was significantly reduced after LHM compared to THM (from 54.5 ± 5.7 mm to 27.1 ± 3.3 mm vs 50.8 ± 7.6 mm to 37.2 ± 6.9 mm, respectively) (p = 0.0001). CONCLUSION: In our experience, LHM is associated with a shorter operative time and a shorter hospital stay, and it is superior to THM in relieving dysphagia. LHM with partial anterior fundoplication should be considered the treatment of choice for achalasia. [ABSTRACT FROM AUTHOR]

Quadrantectomy with axillary-node dissection is the treatment of choice for early-stage breast cancers. The minimally invasive approach to axillary dissection has the theoretical prerequisite to be oncologically correct, while ensuring a better cosmetic result and causing less psychological distress. A prospective, randomised study was carried out to assess the feasibility and the preliminary results of video-assisted axillary-node dissection. Quadrantectomy and video-assisted axillary-node dissection (study group = 10 patients) was compared with standard quadrantectomy and axillary-node dissection (control group = 12 patients operated on during the same period of time). The early outcomes were analysed, taking into account the following parameters: patient's age, ASA group, staging, operating time, number of nodes harvested, postoperative pain, postoperative course (complications, lymphatic drainage, upper-limb mobility), hospital stay and cosmetic results at 6 months. Follow-up was 43–70 months in the study group and 43–64 months in the control group. [ABSTRACT FROM AUTHOR]

The article reports on the RAS proteins observed in HT-29 colorectal carcinoma cells. Topics mentioned include the diagnosis of colorectal cancer, the genetics of guanosine triphosphatase (GTPase), and the effectiveness of Cetuximab drugs in colorectal carcinoma treatment. Also mentioned are the prevention of cancer cells proliferation and the effects of Ras mutations.