The mitogen-activated protein/extracellular signal-regulated kinase kinase 1/2 inhibitor AZD6244 (ARRY-142886) enhances the radiation responsiveness of lung and colorectal tumor xenografts.

Purpose: Novel molecularly targeted agents, given in combination with radiotherapy, have the potential to increase tumor response rates and the survival of patients with lung cancer. AZD6244 is a potent and selective inhibitor of mitogen-activated protein kinase (MAPK) kinase 1/2 (MEK1/2), a critical enzyme within the MAPK/extracellular signal-regulated kinase (ERK) signaling pathway that regulates the proliferation and survival of tumor cells.

Experimental Design: This study examined the potential benefit of combining AZD6244 with fractionated radiotherapy using human lung and colon carcinoma xenograft models.

High serum galectin-3 in advanced melanoma: preliminary results.

Background: Galectin-3 (Gal-3) is a member of the family of beta-galactoside-binding mammalian lectins, and has been implicated in tumour invasion and metastatic process in vitro and in vivo.

Aim: To determine whether an increase in serum Gal-3 production could be found in patients with advanced metastatic melanoma.

Methods: We collected 18 sera from patients with AJCC stage IV metastatic melanomas and 20 sera from healthy volunteers.

Reversing hypoxic cell chemoresistance in vitro using genetic and small molecule approaches targeting hypoxia inducible factor-1.

The resistance of hypoxic cells to conventional chemotherapy is well documented. Using both adenovirus-mediated gene delivery and small molecules targeting hypoxia-inducible factor-1 (HIF-1), we evaluated the impact of HIF-1 inhibition on the sensitivity of hypoxic tumor cells to etoposide. The genetic therapy exploited a truncated HIF-1alpha protein that acts as a dominant-negative HIF-1alpha (HIF-1alpha-no-TAD).

Expression of galectin-3 in primary and metastatic melanoma: immunohistochemical studies on human lesions and nude mice xenograft tumors.

Galectins are a large family of proteins which bind galactoside-containing glycans. Their role in cancer seems to be important since members of the family may mediate cell adhesion and modulate cell growth. Galectin-3 (Gal-3) is expressed in the nucleus, in the cytoplasm and on the cell surface, and can also be secreted into the extracellular matrix.

Multifaceted role of galectin-3 on human glioblastoma cell motility.

Astrocytic tumors' aggressiveness results from an imbalance between cell proliferation and cell death favoring growth, but also from the propensity of tumor cells to detach from the primary tumor site, migrate, and invade the surrounding parenchyma. Astrocytic tumor progression is known to be associated with an increased expression of galectin-3. We investigated in cell culture how galectin-3 expression affects astrocytoma cell motility.

Effects of different cellulose derivatives on drug release mechanism studied at a preformulation stage.

As a matter of fact, in vitro dissolution is well known to be the method of choice for the pharmaceutical industry to develop effective medicines. However, many experiments must be performed all along a new product life and they represent an overcharge of work for researchers. The purpose of this paper was to assess the relevance of new parameters obtained during preformulation stage by Nuclear Magnetic Resonance (NMR) experiments to better understand drug release mechanism.

Contributions of AMPA and GABA(A) receptors to the induction of NMDAR-dependent LTP in CA1.

The contributions of (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and gamma-aminobutyric acid (GABA[A]) receptors in the induction of long-term potentiation (LTP) have been studied in the CA1 region of the rat hippocampus. The results suggest that: (1) in physiological conditions, AMPARs are necessary for the induction of N-methyl-D-aspartate receptor (NMDAR)-dependent LTP since LTP cannot be elicited in the presence of the AMPAR antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Although a NMDAR-dependent LTP occurs in the presence of a GABA(A) antagonist and high concentrations of divalents cations, blockade of AMPARs leads to a voltage-dependent calcium channels (VDCC)-dependent LTP since its induction is blocked by nifedipine and not by APV.

[Primary exocrine pancreatic insufficiency in the adult. Presentation of a case].

The authors report the case of a 37-year-old female complaining of chronic diarrhea since childhood. She had gross steatorrhea and azotorrhea . Pancreatic function tests using secretin and cholecystokinin-pancreozymin stimulation, and analysis of pure pancreatic juice collected under secretin stimulation proved exocrine pancreatic insufficiency.

[Rupture of an aneurysm of the splenic artery into the pancreas, a rare cause of gastrointestinal bleeding (author's transl)].

In a 73 year old man, repeated gastrointestinal haemorrhages first attributed to peptic oesophagitis, recurred despite anti-reflux surgery. Upper endoscopy being negative, arteriography was performed which revealed the presence of a fissured aneurysm of the splenic artery. This was successfully treated by left splenopancreatectomy.

[A case of hepatocholangitis (author's transl)].

Inflammation localised to the hepatic duct in the region of the neck of the gallbladder is rare. Regression of the lesions after cholecystectomy authentified its purely inflammatory nature. Its interest comes from possible confusion with carcinoma of the common bile duct.

[Surgical treatment of Crohn disease of the colon. (38 cases) (author's transl)].

From 1959 to december 1972 thirty-eight patients out of sixty having Crohn disease of the colon alone or with ileal and/or rectal involvement were operated upon. We had four post-operative deaths and one a long time after the intervention, but in relation with the initial Crohn disease. These thirty-eight patients had sixty-seven operations.

[Medical mangement of Crohn's disease (author's transl)].

Medical management of Crohn's disease is above all symptomatic. According to the severeness of the case, treatment varies and may be simple (regimen, antidiarrheic agents and sulfamid drugs) or more sophisticated (continous parenteral alimentation). Sulfamids and antibiotics have a definite although temporary action.

[Haematologic disorders in Crohn's disease (author's transl)].

Anemia is the most commonly haematologic disorder observed in Crohn's disease. Secondary megaloblastic anemia related to a nutritional deficiency of vitamin B 12 and/or folic acid is a rare condition as well as auto-immune haemolytic anemia. Iron lack microcytic hypochromic anemia is far more frequent.

[Extra intestinal manifestations of Crohn's disease (author's transl)].

The extra intestinal manifestations of Crohn's disease (CD) are not devoid of interest. They can, by themselves, aggravate the CD. Some of them have to be searched systematically (urinary complications, spondylarthritis and sacro-iliac arthritis).

[Findings by baryum enema in granulomatous colitis and ileocolitis. A review based upon 60 cases (author's transl)].

Radiological aspects of colonic involvement in 60 patients whose disease has been followed up during several years are described. The typical radiological findings have been observed with their usual frequency. This study also confirmed the persistancy of the radiological findings in the chronic stage and the frequency of recurence in the two first years after surgery.

[Crohn's disease of the colon. History].

During the 18th, 19th, and at the beginning of the 20th century, various observations of inflammatory lesions of the colon and small intestine were published, which were different of tuberculosis to which was at that time attributed every chronical small intestinal inflammatory disease. It was only in 1932, that in a very important paper, Crohn, Ginsburg and Oppenheimer defined the terminal ileitis, afterwards called regional enteritis, and finally more simply Crohn's disease. Twenty years later, in 1952, Crohn's disease of the colon, confused until that date with colonic tuberculosis and with ulcerative colitis, was also identified as a separate entity.

Effects of somatostatin on the external secretion of the pancreas of the rat.

The effects of somatostatin on the secretions of the exocrine pancreas were studied in anesthetized and conscious fistula rats. Somatostatin resulted in a dose-dependent decrease of basal secretion (flow, bicarbonate, protein) in conscious rats. In anesthetized rats, basal secretion was initially augmented by bolus injections of 10 to 50 microgram per kg and was subsequently decreased by venous infusions of somatostatin at 1.