NANOG modulates stemness in human colorectal cancer.

NANOG is a stem cell transcription factor that is essential for embryonic development, reprogramming normal adult cells and malignant transformation and progression. The nearly identical retrogene NANOGP8 is expressed in multiple cancers, but generally not in normal tissues and its function is not well defined. Our postulate is that NANOGP8 directly modulates the stemness of individual human colorectal carcinoma (CRC) cells. Stemness was measured in vitro as the spherogenicity of single CRC cells in serum-free medium and the size of the side population (SP) and in vivo as tumorigenicity and experimental metastatic potential in NOD/SCID mice. We found that 80% of clinical liver metastases express a NANOG with 75% of the positive metastases containing NANOGP8 transcripts. In all, 3-62% of single cells within six CRC lines form spheroids in serum-free medium in suspension. NANOGP8 is translated into protein. The relative expression of a NANOG gene increased 8- to 122-fold during spheroid formation, more than the increase in OCT4 or SOX2 transcripts with NANOGP8 the more prevalent family member. Short hairpin RNA (shRNA) to NANOG not only inhibits spherogenicity but also reduces expression of OCT4 and SOX2, the size of the SP and tumor growth in vivo. Inhibition of NANOG gene expression is associated with inhibition of proliferation and decreased phosphorylation of G2-related cell-cycle proteins. Overexpression of NANOGP8 rescues single-cell spherogenicity when NANOG gene expression is inhibited and increases the SP in CRC. Thus, NANOGP8 can substitute for NANOG in directly promoting stemness in CRC.

Angiotensin II-mediated vasodilation is reduced in adult spontaneously hypertensive rats despite enhanced expression of AT2 receptors.

1. The vasodilator action of angiotensin (Ang) II has not yet been demonstrated in spontaneously hypertensive rats (SHR), nor have any possible changes in this response during the development of hypertension. 2. In the present study, the vasodilator effect of AngII was evaluated in the rat isolated, preconstricted mesenteric arterial bed (MAB) from 6- (young) and 24-week-old (adult) SHR and compared with effects on MAB from age-matched normotensive rats (control). 3. Angiotensin II (10-300 nmol) induced vasodilation in noradrenaline (NA)-preconstricted MAB that was greater in vessels from young compared with adult rats in both the control and SHR groups. Angiotensin II-induced vasodilation was reduced by the angiotensin AT(2) receptor antagonist PD 123319 (10 micromol/L), the angiotensin-(1-7) receptor antagonist A779 (1 micromol/L) and the bradykinin B(2) receptor antagonist HOE-140 (0.01 micromol/L), but not by the AT(1) receptor antagonist losartan (30 micromol/L). Expression of AT(2) receptors was weak in vessels from adult control rats compared with that in young control rats, whereas in young SHR AT(2) receptor expression was increased compared with that in young control rats. This increased expression of AT(2) receptors was maintained in adult SHR and there was no significant difference in AT(2) receptor expression between young and old SHR. 4. The findings of the present suggest that AngII induces an AT(2) receptor-mediated vasodilator effect in the MAB via activation of angiotensin-(1-7) and bradykinin receptors, an action that is reduced in adult control rats and adult SHR. In adult control rats, the attenuated response of AngII is probably due to endothelial dysfunction and reduced expression of AT(2) receptors, whereas in adult SHR it is associated with endothelial dysfunction alone. Increased expression of AT(2) receptors in SHR may represent a counteracting response for modulating blood pressure.

Deletion 5p11 accompanied by multiple numerical changes in testicular lymphoma.

We describe a case of testicular B cell lymphoma with deletion of chromosome 5, del(5)(p11), as a sole structural abnormality. Histopathological diagnosis of the tumor was a high-grade lymphoma of the diffuse type containing cells positive for B cell specific antigen (CD20) and negative for the leukocyte common antigen (CD45). Deletion 5p may define the region of a tumor suppressor gene that could be associated with tumor progression and invasiveness and may serve as an indicator of poor prognosis in testicular lymphomas.

Pathological and karyotypic abnormalities in advanced gastric carcinomas.

Twenty samples of stomach cancers were analyzed by conventional cytogenetic and histopathological techniques. Nineteen tumors were diagnosed as adenocarcinomas and one as an adenosquamous carcinoma. Multiple and complex chromosomal abnormalities were found in the cases evaluated cytogenetically. This heterogeneity of chromosomal changes appears to indicate a certain correlation with tumor progression. Histological analysis showed a distinctive growth pattern of gastric cancer samples and a potential for invasiveness and recurrence for all tumors as well as a poor prognosis.

[Hernia hiatal. Detection of gastroesophageal reflux with the telemetric Heidelberg capsule]. / Contribución al estudio de la hernia hiatal. Detección de reflujo gastroesofágico con cápsula telemétrica de Heidelberg.

120 patients with upper gastrointestinal symptoms were studied and submitted to gastric secretory tests, upper gastrointestinal X-rays and endoscopy. Gastroesophageal reflux was assessed by means of a Heidelberg telemetric capsule. 60 patients had hiatal hernia. Gastroesophageal reflux was present in 63.33%. 76% of the patients with hiatal hernia had gastroesophageal reflux, especially on those with small hernias and on the 5th and 6th decade of life. Gastric hiperacidity facilitates the incidence and presence of reflux. X-rays and endoscopy allowed us to diagnose diseases at the gastroesophageal junction. The correlation between these 2 methods and the presence or not of reflux, allowed differentiation between patients with organic diseases and patients with "functional" symptoms.