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Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
Timely publication of journal: Publication of manuscripts and bringing out the issue in time is one of the positive aspects of JCDR and is possible with strong support team in terms of peer reviewers, proof reading, language check, computer operators, etc. This is one of the great reasons for authors to submit their work with JCDR. Another best part of JCDR is "Online first Publications" facilities available for the authors. This facility not only provides the prompt publications of the manuscripts but at the same time also early availability of the manuscripts for the readers.
Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."
Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011
Dr. Shankar P.R.
"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."
Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011 Anuradha
Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.
Dr. Anuradha
E-mail: anuradha2nittur@gmail.com
On Jan 2020
Original article / research
Full Version
Expression Of P53, Ck7, Ck20 And Rb Proteins in Oesophageal Squamous Cell Carcinoma In Iran
Correspondence Address :
Seyed Mohammad Mohseni Mehran (DVM,PhD)
Department of Physiology,Rasht Medical School Guilan University of Medical Sciences,Rasht, (Iran)Tel:+981316690099
,Fax: +981316690007,Email: mohsenimehran@gums.ac.ir
Background
Cancer of the oesophagous is one of the most malignant tumours and has a poor prognosis. The p53 and retinoblastoma (Rb) genes are involved in the regulation of the cell population by the suppression of cell proliferation. Our aim was to show whether the expression of the p53, Ck7, Ck20 and Rb genes could be used as a prognostic indicator in oesophageal squamous cell carcinoma.
Methods
Samples obtained from 49 patients undergoing subtotal or total oesophagectomy were mmunohistochemically stained for studying the expression of the p53, Ck7, Ck20 and Rb genes and then the clinicopathological characteristics of those patients were investigated.
Results
P53 was positive in 40.4% of the patients (more than 20% of the tumour cells were stained), 12.8% were partially positive and in others, it was negative. Immunohistochemical staining for the expression of the Ck7, Ck20 and Rb genes in our samples was negative. P53 seemed to have significance in the prognosis of the cancer but Ck7, Ck20 and Rb expression did not have prognostic significance in the surgical treatment of oesophageal cancer.
p53, Ck7 (Cytokeratin 7), Ck20 ( Cytokeratin 20), Rb, Oesophageal Squamous Cell Carcinoma (ESCC)
Introduction
Cancer of oesophagus is the 10th most common malignancy in the world, the second ranking after heart infarction according to the last report of the EMRO's regional office for the Eastern Mediterranean Organization (1). Cancer of the oesophagus shows a great variation in geographical distribution. It is the fifth most common cancer in developing countries and about 300,000 new cases are diagnosed every year. Epidemiological studies have identified several-high incidence areas in China, Singapore, Iran, Russia, Puerto Rico, Chile, Brazil, Switzerland, France and South Africa, but the causes for striking geographical variations in the incidence of human oesophageal cancer remain obscure. One of the features of squamous cell carcinoma of the oesophagus is the fragmentation of its incidence into low risk and high risk areas, based on geographical location. Some of the low risk areas include North America, countries in Western Asia and Northern and Southern Europe, where the incidence rates range from 1.5 to 6.0/100,000 and well defined high risk areas such as South Africa, China, Iran and countries in Eastern Africa, where the incidence rates range from 10 to 25/100,000 (2),(3),(4),(5) Iran, one of the areas with the highest rate of Oesophageal Squamous cell carcinoma (ESCC) cases in the north of Iran, especially the Guilan province, is a region with high incidence. ESCC most commonly show morphological to squamous cell carcinoma of other regions of the body like cervix and oral cavity. It is generally agreed that tobacco, alcohol, hot black tea (bad habit in some regions in the north east of Iran) and alcohol consumption in Europe are the major environmental risk factors for the development of ESCC [6,7,8]. However, some patients developed ESCC even without these 4 risk factors. Hence, this fact suggests that additional causes such as genetic predisposition, diet or oncogenic viruses may also help cells to override or escape the physiological mechanism of proliferation control. p53 protein is a 53-kd nuclear phosphoprotein encoded by the gene that locates on the short arm of chromosome 17 (17p13.1).Wild- type p53 is known to suppress cell proliferating activity in normal tissues .In tumour tissues, however, this function disappears because of mutation of the genes, as observed in tumours originating from the colon, lung, breast, ovary brain, liverand the haematopoietic tissues. p53 mutation has been identified with a frequency of 8% to 85% in studies of oesophageal cancer. Retinoblastoma (Rb) also is linked to a tumour suppressor gene located on the long arm of chromosome 13 (13q14.2)..Rb protein, a 110- to 114 –kd nuclear phosphoprotein, is expressed in most normal cells. The function of this protein depends on its phosphorylation status. An underphosphosphorylated form of the Rb protein is identified mainly in resting cells, whereas the hyperphorylated form is present in proliferating cells. Cellular level Rb protein may vary during the cell cycle, but the inhibitory effect of Rb protein on cell cycle progression can be abrogated during tumour development.Complete absence of Rb protein immunoreactivity indicates Rb gene alteration. [9,10] The use of cytokeratins 20 (CK20) and 7 (CK7) was proposed to identify the primary sites in this situation. Ductal breast carcinomas and lung and non-mucinous ovarian adenocarcinomas showed significant differences in CK7 expression when primary and metastatic tumours were compared. CK20 positivity alone indicates the metastatic spread of adenocarcinoma in several organs. CK7 negativity is consistent with metastases of adenocarcinomas in the lungs, ovaries, liver or serous membranes. CK20/7 phenotyping of adenocarcinomas is a useful diagnostic tool if based on algorithmic and probabilistic (11)
Sample collection
A total of forty- nine formalin –fixed paraffin embedded samples of ESCC were collected from the 2005 – 2007 surgical pathology archives of Rasht Razi Hospital, Pour Sina Hospital, Golsar Hospital, Dr.Satari (Sina) Pathobiology lab and Dr.Saffari (Fouman) Pathobiology lab. The patients visited the Rasht Razi Hospital from various parts of the Guilan province, which is a major center of Gastro Intestinal diseases. The selection was made according to the availability of fixed tumour tissues and clinico-pathological data. The paraffin-embedded blocks were obtained from surgical (total or sub total oesophagotomy) or biopsy specimens of oesophageal cancer patients. First, Hematoxylin and Eosin –stained slides were prepared by expert histopathologists to confirm ESCC and tumour stage. The carcinomas were further subclassified into 3 categories according to standard histological criteria: well differentiated, moderately differentiated and poorly differentiated. Then, the remaining samples were re-examined for Immunohistochemical studies. Information of age and gender was recorded.
Immunohistochemistry
Immunohistochemical studies were performed on 4 to 5-μm tissue sections which were mounted on silanized slides using commercially available monoclonal antibodies: anti-p16INK4A (clone 6H12) and anti-Rb (clone IF8) obtained from Novocastra (Newcastle-upon-Tyne, UK) and anti-p53 (Clone DO-7) from DAKO (Glostrup, Denmark). Immunohistochemical staining was conducted using the DAKO system (Envision +dual link system – HRP) according to the manufacturer’s instructions. Briefly, dewaxed sections were heated in a microwave oven for 2X for 5 minutes in 10 mM citrate-Na (pH 6.0). After incubation with blocking serum for 20 minutes, the sections were incubatedwith primary antibodies which are described above for 1 hour at room temperature with an antibody dilution of CK7 and CK20 and anti-p53 and anti-Rb. After further incubation with biotynilated link antibody and peroxidase-labeled streptavidin, the staining was developed by reaction with DAB+ chromogenic solution diluted 50:1(DAKO, Glostrup, Denmark) under microscopic control. In each experiment, a negative control in which the primary antibodies were replaced by preimmune mouse immunoglobulin G (IgG), and positive control slides were included. Nuclear staining was considered to be positive for p53, Rb, Ck7 andCk20. A tumour was recorded to be positive if more than 10% of the tumour cells showed immunoreactivity. The staining characteristics were compared with adjacent nonneoplastic squamous epithelium. In normal epithelium, pRb is expressed in the nucleus of epithelial cells which are located in the parabasal and suprabasal layers. Tumour samples were scored as positive when staining was observed in more than 30% of the tumour cell nuclei. p53 expression was rarely detectable in the normal epithelium. We used a 10% cut off for nuclear p53 staining
The mean age at diagnosis was 64 (range 35 to 81) years and there were 22 female patients and 27 male patients. p53 expression was completely positive in 19 patients (40.4%), partially positive in 6 patients (12.8%) and negative in 22 patients (22%).
Expression of the markers of both SCC of the oesophagus and their associated pre-malignant lesions can be influenced by several factors. These factors could be related to different processes involved in the initiation and progression of the cancer. Factors implicated in the defense mechanisms against toxic intermediates as well as parameters related to inflammatory reactions are often analyzed as markers in the early events of cancer development. Moreover, the inactivation of the protein products of certain genes which are responsible for cell cycle regulation and cellular differentiation are important biomarkers in the development of cancer (12). In this study, we analyzed P53 mutation patterns in the ESCC samples of 49 patients living in the North of Iran (Guilan ,Rasht).The prevalence of mutations was 20 to 70 % ( the overexpression of p53 showed the characteristic nuclear location with variations in the staining intensity and in the number of positive cells). 19 of the 49 tumours were more than 70% p53 positive and 6 of the 49 tumours were less than 20% positive; the majority of p53 –positive tumours showed definite p53 immunostaining in 20% to 70% of the tumour cells, which is similar to other studies in Iran (50 to 65%) and France (over 80%) or in Eastern countries, such as China (42–70%) . These findings were reported from southern Brazil also (13).
Squamous cell carcinoma of the oesophgous is one of the most malignant diseases and has a dismal prognosis .This poor prognosis is believed to be associated with the structural characteristics of the oesophagus ie; lack of serosa and abundant lymphatic channels. Patients in whom the p53 expression was high had greater tumour diameter, deeper tumour invasion and worse prognosis as compared to patients in whom the p53 expression was low. Metastatic adenocarcinoma from an unknown primary site is a common clinical problem. The use of cytokeratins 20 (CK20) and 7 (CK7) was proposed to identify the primary sites in this situation. Most tumours retained the CK20 phenotype during metastasis. CK20 positivity alone indicates the metastatic spread of adenocarcinoma in several organs. CK7 negativity was consistent with metastases of adenocarcinomas in the lungs andovaries. Ck7 and Ck20 expression was not seen in our samples may be because it was negative in all our patients.
This paper was financially supplied by a research grant from the Gastrointestinal and Liver Diseases Research Center (GLDRC), Guilan University (Medical Sciences). We would also like to express our deep gratitude toward, Dr.P.Sattari, Dr.Askari, Dr.S.Saffari ,Dr.F.Ghasami,Dr.R.Jaffarishakib and Dr.Haydarzadeh for their technical support
Conflict Of Interest: Non declare
Blot WJ.Epidemiology and genesis esophageal cancer . Semin oncol:1999;15:72
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