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Adjuvant chemotherapy aims at eradicating tumour cells sometimes present after radical surgery for a colorectal cancer (CRC) and thereby diminish the recurrence rate and prolong time to recurrence (TTR). Remaining tumour cells will lead to recurrent disease that is usually fatal. Adjuvant therapy is administered based upon the estimated recurrence risk, which in turn defines the need for this treatment. This systematic overview aims at describing whether the need has decreased since trials showing that adjuvant chemotherapy provides benefits in colon cancer were performed decades ago. Thanks to other improvements than the administration of adjuvant chemotherapy, such as better staging, improved surgery, the use of radiotherapy and more careful pathology, recurrence risks have decreased. Methodological difficulties including intertrial comparisons decades apart and the present selective use of adjuvant therapy prevent an accurate estimate of the magnitude of the decreased need. Furthermore, most trials do not report recurrence rates or TTR, only disease-free and overall survival (DFS/OS). Fewer colon cancer patients, particularly in stage II but also in stage III, today display a sufficient need for adjuvant treatment considering the burden of treatment, especially when oxaliplatin is added. In rectal cancer, neo-adjuvant treatment will be increasingly used, diminishing the need for adjuvant treatment.

Genes for the human small nuclear RNA U2 are present within 6.2-kilobase-pair-long tandem repeats. The haploid human genome contains approximately 20 such repeats, organized in one or a few very large clusters.The small nuclear RNAs (snRNAs) comprise a family of highly conserved RNA species, present in the nucleus of the eukaryotic cell (reviewed in ref. 1). Circumstantial evidence suggests that U1 RNA and possibly other snRNA species serve their function in connection with the maturation of heterogeneous nuclear RNA to spliced mRNA (2-4). Considerable effort has been devoted to studies of human snRNA genes (5-17). One main conclusion from these studies is that the mammalian cell contains numerous loci that are related to the snRNAs, many of which appear to represent pseudogenes. Because of the presence of numerous pseudogenes for snRNA, it has been difficult to isolate and determine the structure of functional mammalian snRNA genes. In the present report, we describe a human locus, designated U2/6, that contains multiple genes for U2 RNA. MATERIALS AND METHODSIsolation of Clones Containing U2 RNA Sequences. The U2/6 clone was obtained from the human genomic DNA library of Lawn (7,18). This library contains fragments generated by partial cleavage with endonucleases Alu I and Hae III inserted with EcoRI linkers. Fragments from the recombinant phage were subcloned using the pBR322 vector. Cloning experiments were carried out according to Swedish guidelines for work with recombinant DNA.DNA Sequence Analysis. The Taq I fragments shown in Fig. LA were cloned in the Cla I site of pBR322 and sequenced according to Maxam and Gilbert (19 Cloning of a Locus for Human U2 RNA. A locus designated U2/6 was isolated from the human DNA library of Lawn (7, 18) and a 4.4-kilobase-pair (kb)-long Pst I fragment was subcloned in the pBR322 vector. A restriction enzyme cleavage map was established for the resulting clone (pU2.6/1) (Fig. 1A) and relevant parts of the fragment were sequenced by the Maxam and Gilbert procedure (19). A comparison between the established sequence and the sequence of rat U2 RNA (22) reveals four differences, which occupy positions 108, 110, 111, and 116.A more detailed analysis of the established U2/6 sequence reveals some interesting features, and the results are presented in Fig. 2 and will be discussed below.Previous studies have shown that snRNA loci often are connected with repetitive sequences belonging to the socalled Alu family (5, 9). To test whether the U2/6 locus also contained such sequences, a DNA probe (Blur 8) (29) was hybridized to fragments of the U2/6 recombinant. The result revealed the presence of an Alu-like sequence and its position is shown in Fig. 1B.The U2/6 Recombinant Is Unstable When Propagated in Escherichia coli. When the U2/6-X recombinant was propagated on a large scale, two populations of phage particles were isolated after CsCl gradient fractionation. Electron microscopic heteroduplex analyses of 27 molecules showed that 6.8 ± 0.4 kb had been deleted from the gen...

Radiotherapy (RT) or chemoradiotherapy (CRT) are frequently used in rectal cancer, sometimes resulting in complete tumor remission (CR). The predictive capacity of all clinical factors, laboratory values and magnetic resonance imaging parameters performed in routine staging was evaluated to understand what determines an excellent response to RT/CRT. A population-based cohort of 383 patients treated with short-course RT (5 × 5 Gy in one week, scRT), CRT, or scRT with chemotherapy (scRT+CT) and having either had a delay to surgery or been entered into a watch-and-wait program were included. Complete staging according to guidelines was performed and associations between investigated variables and CR rates were analyzed in univariate and multivariate analyses. In total, 17% achieved pathological or clinical CR, more often after scRT+CT and CRT than after scRT (27%, 18% and 8%, respectively, p < 0.001). Factors independently associated with CR included clinical tumor stage, small tumor size (<3 cm), tumor level, and low CEA-value (<3.8 μg/L). Size or stage of the rectal tumor were associated with excellent response in all therapy groups, with small or early stage tumors being significantly more likely to reach CR (p = 0.01 (scRT), p = 0.01 (CRT) and p = 0.02 (scRT+CT). Elevated level of carcinoembryonic antigen (CEA) halved the chance of response. Extramural vascular invasion (EMVI) and mucinous character may indicate less response to RT alone.

The human DNA library of Lawn et al. (1978) was screened for sequences complementary to the small nuclear (sn) RNA U4. Several positive clones were identified by screening 100 000 recombinants, indicating that U4 sequences like other snRNA sequences are dispersed in the human genome. One recombinant was characterized in detail by subcloning a Bg/II fragment 1.9 kilobases (kb) long in the pBR322 plasmid. The subcloned fragment was partially sequenced and the results revealed a pseudogene for U4 RNA. The pseudogene was found to have a remarkable structure; it contains a sequence that, except in two positions, matches the first 68 nucleotides of the human U4 RNA sequence and the pseudogene is, moreover, flanked by perfect direct repeats 20 bp long. The results support the model of van Arsdell et al. (1981) suggesting that certain snRNA pseudogenes arise by reverse transcription of the RNA followed by integration of the cDNA copy at a new chromosomal locus.