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Objectives The recurrence of rectal cancer or its resistance to neoadjuvant treatment develops due to the adaptation to hypoxia, apoptosis or autophagy. Survivin, one of the inhibitors of apoptosis; Beclin 1, which is a positive regulator in the autophagy pathway; and hypoxia-inducible factor-1α (HIF-1α) and carbonic anhydrase-9 (CA9), which are associated with tumor tissue hypoxia, may be related to resistance to treatment. Our aim was to evaluate the potential tumor markers that may help to monitor the response to neoadjuvant treatment in locally advanced rectal cancer (RC). Methods Twenty-five patients with locally advanced RC were included in the study. Gene expression and protein levels of Beclin 1, Survivin, HIF-1α, and CA9 were analyzed in fresh tissue specimens and blood samples. The relationships of these markers to tumor staging and regression grade were evaluated. Results Higher blood CA9 gene expression levels and lower blood HIF-1α protein levels were found in the response group according to tumor regression grade. After neoadjuvant treatment, tissue Beclin 1 and blood Survivin gene expressions and tissue CA9, blood Beclin 1 and blood HIF-1α protein levels decreased significantly. Conclusion Beclin 1, Survivin, HIF-1α ve CA9 may help to predict the effects of the applied treatment approach.

Tangkuban Parahu is an active stratovolcano located 17 km north of the city of Bandung in the province west Java, Indonesia. All historical eruptive activity at this volcano has been confined to a complex of explosive summit craters. About a dozen eruptions-mostly phreatic events- and 15 other periods of unrest, indicated by earthquakes or increased thermal activity, have been noted since 1829. The last magmatic eruption occurred in 1910. In late 1983, several small phreatic explosions originated from one of the summit craters. More recently, increased hydrothermal and earthquake activity occurred from late 1985 through 1986. Tilt measurements, using a spirit-level technique, have been made every few months since February 1981 in the summit region and along the south and east flanks of the volcano. Measurements made in the summit region indicated uplift since the start of these measurements through at least 1986. From 1981 to 1983, the average tilt rate at the edges of the summit craters was 40–50 microradians per year. After the 1983 phreatic activity, the tilt rate decreased by about a factor of five. Trilateration surveys across the summit craters and on the east flank of the volcano were conducted in 1983 and 1986. Most line length changes measured during this three-year period did not exceed the expected uncertainty of the technique (4 ppm). The lack of measurable horizontal strain across the summit craters seems to contradict the several years of tilt measurements. Using a point source of dilation in an elastic half-space to model tilt measurements, the pressure center at Tangkuban Parahu is located about 1.5 km beneath the southern part of the summit craters. This is beneath the epicentral area of an earthquake swarm that occurred in late 1983. The average rate in the volume of uplift from 1981 to 1983 was 3 million m3 per year; from 1983 to 1986 it averaged about 0.4 million m3 per year. Possible causes for this uplift are increased pressure within a very shallow magma body or heating and expansion of a confined aquifier.

Human fibroproliferative disorders like hypertrophic scarring of the skin are characterized by increased contractility and excess extracellular matrix synthesis. A beneficial role of transforming growth factor (TGF)-beta in wound healing was proposed; however, chronic stimulation by this cytokine leads to fibrosis. In the present report, the intracellular TGF-beta signaling in fibroblasts derived from hypertrophic scars and normal skin was examined. In an attempt to intervene in profibrogenic TGF-beta functions, ectopic expression of Smad7 or dominant negative Smads3/4 completely inhibited contractility of scar-derived and normal fibroblasts after suspension in collagen gels. Both cell types displayed constitutive Smad2/3 phosphorylation and (CAGA)9-MLP-Luc activity with expression and phosphorylation of Smad3 being predominant in hypertrophic scar-derived fibroblasts. Down-regulation of intrinsic signaling with various TGF-beta antagonists, e.g. soluble TGF-beta receptor, latency-associated peptide, and anti-TGF-beta1 antibodies, confirms autocrine TGF-beta stimulation of both cell populations. Further, Smad7 expression inhibited alpha1 (I) collagen and alpha-smooth muscle actin expression. In summary, our data indicate that autocrine TGF-beta/Smad signaling is involved in contractility and matrix gene expression of fibroblasts from normal and hypertrophic scars. Smad7 inhibits these processes and may exert beneficial effects on excessive scar formation.