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      Differential Expression of Cholecystokinin A Receptor in Gallbladder Cancer in the Young and Elderly Suggests Two Subsets of the Same Disease?

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          Abstract

          Background. Cholecystokinin type A receptor (CCKAR) is known to be overexpressed in variety of human malignancies but information regarding its expression in gallbladder cancer (GBC) is limited. Attempts were now made to investigate expression pattern of CCKAR mRNA and protein in controls and GBC patients and correlate it with various clinicopathological parameters following surgical resection. Materials and Methods. Gallbladder tissue samples from 64 subjects (GBC: 39; control: 25) were studied. Expression of CCKAR mRNA was evaluated by reverse transcriptase-polymerase chain reaction and confirmed using real-time polymerase chain reaction. Protein expression was studied by enzyme-linked immunosorbent assay. Results. Significantly higher expression of CCKAR mRNA ( P < 0.0001) and protein ( P < 0.0001) was observed in GBC tissues. Overexpression was also observed for stage III and in moderately and poorly differentiated tumors. When the clinicopathological parameters were compared, we found age dependent decrease in CCKAR expression. Relatively higher expression of CCKAR was observed in younger patients (age < 45 years) having more aggressive disease when compared with elderly ones (age ≥ 45 years). Conclusions. Age related differential expression of CCKAR in GBC may suggest two possible variants of the disease in this endemic belt.

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          Most cited references 36

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          The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM.

          The American Joint Committee on Cancer and the International Union for Cancer Control update the tumor-node-metastasis (TNM) cancer staging system periodically. The most recent revision is the 7th edition, effective for cancers diagnosed on or after January 1, 2010. This editorial summarizes the background of the current revision and outlines the major issues revised. Most notable are the marked increase in the use of international datasets for more highly evidenced-based changes in staging, and the enhanced use of nonanatomic prognostic factors in defining the stage grouping. The future of cancer staging lies in the use of enhanced registry data standards to support personalization of cancer care through cancer outcome prediction models and nomograms.
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            Peptide receptors as molecular targets for cancer diagnosis and therapy.

            During the past decade, proof of the principle that peptide receptors can be used successfully for in vivo targeting of human cancers has been provided. The molecular basis for targeting rests on the in vitro observation that peptide receptors can be expressed in large quantities in certain tumors. The clinical impact is at the diagnostic level: in vivo receptor scintigraphy uses radiolabeled peptides for the localization of tumors and their metastases. It is also at the therapeutic level: peptide receptor radiotherapy of tumors emerges as a serious treatment option. Peptides linked to cytotoxic agents are also considered for therapeutic applications. The use of nonradiolabeled, noncytotoxic peptide analogs for long-term antiproliferative treatment of tumors appears promising for only a few tumor types, whereas the symptomatic treatment of neuroendocrine tumors by somatostatin analogs is clearly successful. The present review summarizes and critically evaluates the in vitro data on peptide and peptide receptor expression in human cancers. These data are considered to be the molecular basis for peptide receptor targeting of tumors. The paradigmatic peptide somatostatin and its receptors are extensively reviewed in the light of in vivo targeting of neuroendocrine tumors. The role of the more recently described targeting peptides vasoactive intestinal peptide, gastrin-releasing peptide, and cholecystokinin/gastrin is discussed. Other emerging and promising peptides and their respective receptors, including neurotensin, substance P, and neuropeptide Y, are introduced. This information relates to established and potential clinical applications in oncology.
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              Carcinoma of the gallbladder.

              Carcinoma of the gallbladder is the most common malignant tumour of the biliary tract and a particularly high incidence is observed in Chile, Japan, and northern India. The aetiology of this tumour is complex, but there is a strong association with gallstones. Owing to its non-specific symptoms, gallbladder carcinoma is generally diagnosed late in the disease course, but if a patient with gallstones experiences a sudden change of symptoms, then a cancer diagnosis should be considered. Treatment with radical or extended cholecystectomy is potentially curative, although these procedures are only possible in 10-30% of patients. There is no role for cytoreductive surgery in this disease. If a gallbladder carcinoma is discovered via pathological examination of tissue samples, then the patient should be examined further and should have radical surgery if the tumour is found to be T1b or beyond. Additional port-site excision is necessary if the patient has already had their gallbladder removed during laparoscopy; however, patients with an intact gallbladder who are suspected to have gallbladder carcinoma should not undergo laparoscopic cholecystectomy. Patients with advanced inoperable disease should receive palliative treatment; however, the role of chemotherapy and radiation in these patients needs further evaluation.
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                Author and article information

                Affiliations
                1Department of Surgical Gastroenterology, King George's Medical University, Lucknow 226003, India
                2Developmental Toxicology Division, Indian Institute of Toxicology Research, Lucknow 226003, India
                3Department of Biochemistry, King George's Medical University, Lucknow 226003, India
                4Department of Biochemistry, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh 462024, India
                5All India Institute of Medical Sciences, Bhopal, Madhya Pradesh 462024, India
                Author notes

                Academic Editor: Saulius Butenas

                Journal
                Biomed Res Int
                Biomed Res Int
                BMRI
                BioMed Research International
                Hindawi Publishing Corporation
                2314-6133
                2314-6141
                2014
                15 June 2014
                : 2014
                4082861 10.1155/2014/625695
                Copyright © 2014 Hasan Raza Kazmi et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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                Research Article

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