Hormonal changes during non-climacteric ripening in strawberry.

In contrast to climacteric fruits, where ethylene is known to be pivotal, the regulation of ripening in non-climacteric fruits is not well understood. In the non-climacteric strawberry (Fragaria anannassa), auxin and abscisic acid (ABA) are thought to be important, but the roles of other hormones suggested to be involved in fruit development and ripening are not clear. Here changes in the levels of indole-3-acetic acid (IAA), ABA, GA1, and castasterone from anthesis to fully ripened fruit are reported. The levels of IAA and GA1 rise early in fruit development before dropping to low levels prior to colour accumulation. Castasterone levels are highest at anthesis and drop to very low levels well before ripening commences, suggesting that brassinosteroids do not play an important role in ripening in strawberry. ABA levels are low at anthesis and gradually rise through development and ripening. The synthetic auxin, 1-naphthaleneacetic acid (NAA), can delay ripening, but the application of GA3, the gibberellin biosythesis inhibitor paclobutrazol, and ABA had no significant effect. IAA and ABA levels are higher in the developing achenes than in the receptacle tissue and may be important for receptacle enlargement and ripening, and seed maturation, respectively. Contrary to a recent report, the biologically active GA4 was not detected. The pattern of changes in the levels of the hormones are different from those reported in another well studied non-climateric fruit, grape, suggesting that a single consistent pattern of hormone changes does not occur in this group of fruit during ripening.

A multicentre study of capecitabine, oxaliplatin plus bevacizumab as perioperative treatment of patients with poor-risk colorectal liver-only metastases not selected for upfront resection.

BACKGROUND: Perioperative chemotherapy improves outcome in resectable colorectal liver-only metastasis (CLM). This study aimed to evaluate perioperative CAPOX (capecitabine-oxaliplatin) plus bevacizumab in patients with poor-risk CLM not selected for upfront resection. PATIENTS AND METHODS: Poor-risk CLM was defined as follows: more than four metastases, diameter >5 cm, R0 resection unlikely, inadequate viable liver function if undergoing upfront resection, inability to retain liver vascular supply, or synchronous colorectal primary presentation. Patients underwent baseline computed tomography, magnetic resonance imaging, and/or positron emission tomography (PET) for staging and received neoadjuvant CAPOX plus bevacizumab, with resectability assessed every four cycles. Primary end point was radiological objective response rate (ORR). RESULTS: Forty-six patients were recruited, of which 91% underwent PET to ensure metastases confined to liver. Following neoadjuvant CAPOX plus bevacizumab, the ORR was 78% (95% confidence interval 63% to 89%). This allowed 12 of 30 (40%) patients with initial nonsynchronous unresectable CLM to be converted to resectability. In addition, 10 of 15 (67%) patients with synchronous resectable CLM underwent liver resection, with four additional patients being observed alone due to excellent response to neoadjuvant therapy. No grade 3-4 perioperative complications were seen. CONCLUSION: Neoadjuvant CAPOX plus bevacizumab resulted in a high response rate for patients with CLMs with poor-risk features not selected for upfront resection and converted 40% of patients to resectability.

Pancreatic cancer--is the wall crumbling?

In spite of advances made in the management of the other more common cancers of the gastrointestinal tract, significant progress in the treatment of pancreatic cancer remains elusive, more so with the recent negative results of several much anticipated randomized trials. Gemcitabine has been a standard treatment for advanced pancreatic cancer since it was shown a decade ago to result in a superior clinical benefit response and survival compared with bolus 5-fluorouracil (5-FU). Since then, clinical trials have explored the pharmacokinetic modulation of gemcitabine by fixed dose administration and the combination of gemcitabine with other cytotoxics or the biological 'targeted' agents. Against a background of numerous negative randomized trials of gemcitabine-based combination treatment, two trials have recently reported modest survival improvements with the use of combination treatment: the United Kingdom National Cancer Research GEMCAP trial of gemcitabine with the orally administered precursor of 5-FU-capecitabine and the National Cancer Institute of Canada Clinical Trials Group PA.3 trial in which the tyrosine kinase inhibitor erlotinib was used with gemcitabine. This review will summarize the results of several recent randomized trials of combination treatment in advanced pancreatic cancer and discuss their implications for clinical practice and for future research in this disease.

5-Fluorouracil can cross brain-blood barrier and cause encephalopathy: should we expect the same from capecitabine? A case report on capecitabine-induced central neurotoxicity progressing to coma.

PURPOSE: Capecitabine is a relatively new oral fluoropyrimidine currently licensed for the treatment of colorectal and breast cancer. RESULTS: It has the advantage of oral administration with good tolerability and comparable activity to intravenous 5-fluorouracil. Central neurotoxicity has been described in 5-fluorouracil-treated patients but there is little data regarding capecitabine. We report here a case of reversible capecitabine-induced encephalopathy progressing to coma. DISCUSSION: Literature on fluoropyrimidine-related neurotoxicity will also be reviewed and possible mechanisms of the drug or its metabolites crossing the blood-brain barrier will be discussed.

Emerging therapies for rectal cancer.

Preoperative treatment with either short-course radiotherapy or chemo-radiotherapy (CRT) is used routinely in some centres to reduce local recurrence rates in patients with operable rectal cancer prior to optimal surgery. However, there is a need for new treatment strategies to further improve the outcomes of these patients, particularly with regard to survival. Advances in the treatment of metastatic disease, such as the use of combination chemotherapy with oxaliplatin and irinotecan, and the targeted agents bevacizumab and cetuximab, have led to clinical research into alternative radio-sensitizers during CRT and the novel use of neo-adjuvant (preoperative) chemotherapy prior to preoperative CRT and surgery. Whilst these remain experimental, it is likely that these will serve as a platform for developing an expanded range of treatment options so that clinicians will be better able to tailor treatment to the needs of different patients.