Hari S. Shukla

Preliminary study of p53 and c-erbB-2 expression in gallbladder cancer in Indian patients

BackgroundThe inactivation of the tumour suppressor gene and activation of the proto-oncogene are the key steps in the development of the human cancer. The p53 and c-erbB-2 are the best examples of it. In the present study, our aim was to determine the role of these genes in the carcinogenesis of gallbladder by immunohistochemistry.MethodsIn all 78 consecutive patients of gall bladder diseases were studied for p53 and c-erbB-2 expression immunohistochemically and their expression was correlated with the age, grades and stages of the disease and presence of stone. An informed consent was obtained in each case. Chi square and z test were applied to see the association of p53 and c-erbB-2 over expression with other clinicopathological factors.ResultsEight (20%) patients of gall bladder cancer were positive for p53 expression and 10 (25%) patients for c-erbB-2. The p53 positivity increased with increasing grade while cerbB-2 positivity decreased with increasing grade of gall bladder cancer. Mean age in cerbB-2 positive cases were lesser as compared to negative cases while p53 did not show such association with age.ConclusionOnly one case of gall bladder cancer co-expressed the p53 and c-erbB-2, thereby suggesting that p53 and c-erbB-2 may have independent role in carcinogenesis of gall bladder cancer. c-erbB-2 over expression in adenoma and younger age group indicates its role as an early event in carcinogenesis of gallbladder. However study of larger sample is required to further validate the results.

Helicobacter pylori and pathogenesis of gallbladder cancer

Background and Aim:  Gallbladder cancer (GBC) is a rare but leading cause of cancer‐related deaths worldwide. The incidence of GBC is increasing at an alarming rate in the Varanasi region, and its etiology remains obscure.

Effect of Prevailing Local Treatment Options of Breast Cancer on Survival Outside Controlled Clinical Trials: Experience of a Specialist Breast Unit in North India

BackgroundThis study aimed at analyzing different treatments of breast cancer (BC) prevalent in the region, their effect on patients’ survival, and discusses the most suitable method within available resources.MethodsThe study was set up at a tertiary care hospital in north India. We retrospectively reviewed data of 473 female BC patients who attended the departments of Surgical Oncology and Radiotherapy from January 1997 to December 1999. Patients with cTNM stage IV and inoperable stage III were included; those who defaulted or were lost to follow-up were excluded. Out of 473 patients, 372 were selected. The selected patients were divided into groups on the basis of place and type of local treatment they received: (1) local excision only, (2) standard breast conservation therapy (BCT), (3) total mastectomy (TM) + axillary lymph node dissection + radiotherapy (RT), and (4) modified radical mastectomy (MRM) + RT. Data regarding recurrence and survival were analyzed in December 2005. Minimum follow-up was 6 years.ResultsOverall recurrence rates were significantly higher in patients operated elsewhere (P <0.0001). Of 194 operated at our Breast Unit, 25 (14.6%) of 171 MRM patients and none of 23 BCT had recurrence. Of 178 patients operated elsewhere, 44 (100%), 6 (42.9%), 41 (41%), and 8 (40%) developed recurrence in groups 1, 2, 3, and 4 respectively. Overall survival was significantly better in patients with MRM at our unit versus TM outside (93.6% vs. 80%).ConclusionsSeveral types of treatment from improper local excision alone, BCT, TM, to a carefully done MRM are prevalent here. Properly done, MRM yields significant local control with survival benefit and appears to remain the gold standard in management of our BC patients.

Cholecystokinin and gastrin receptors targeting in gastrointestinal cancer

Cholecystokinin and Gastrin are amongst the first gastrointestinal hormone discovered. In addition to classical actions (contraction of gallbladder, growth and secretion in the stomach and pancreas), these also act as growth stimulants for gastrointestinal malignancies and cell lines. Growth of these tumours is inhibited by antagonists of the cholecystokinin and gastrin receptors. These receptors provides most promising approach in clinical oncology and several specific radiolabelled ligands have been synthesized for specific tumour targeting and therapy of tumours overexpressing these receptors. Therefore, definition of the molecular structure of the receptor involved in the autocrine/paracrine loop may contribute to novel therapies for gastrointestinal cancer. Hence, this review tries to focus on the role and distribution of these hormones and their receptors in gastrointestinal cancer with a brief talk about the clinical trial using available agonist and antagonist in gastrointestinal cancers.

Discovery of Helicobacter pylori in gallbladder

Helicobacter pylori, a gramnegative and microaerophilic organism, is transmitted from person-to-person through the feco-oral route and colonizes the stomach. The organism persists in the healthy host in equilibrium, which is disturbed at times, leading to formation of peptic ulcer and gastric cancer. Presence of H. pylori in the biliary tree of a small proportion of individuals has led to the conjecture that it is a potential cause of gallbladder disease. The exact pathway of how the organism reaches the gallbladder is unclear. It could reach the gallbladder directly from the stomach or through the portal blood circulation. In contrast to the stomach, colonization of the gallbladder is unlikely due to the alkaline pH of bile, H. pylori being known to thrive at the low pH of gastric juice. Thereare several tests to confirm presence ofH. pyloriin the stomach. These include rapid urease test, and demonstration of the bacterium on histology and culture of gastric biopsy, and positive urea breath ( 13 Co r 14 C) test. Molecular tests identify the genes of H. pylori in the tissue. Immunological evidence of H. pyloriinfection is provided by presence ofH. pylori-specific IgG and IgM antibodies in the blood. Similar tests can be used to demonstrate H. pylori in gallbladder and bile. Demonstration of H. pylori in gallbladder has been attempted directly by culture of gallbladder, bile or gallbladder mucosal scrappings or demonstration of the bacillus on histology of gallbladder. Demonstration of Helicobacter in

In Silico Profiling of the Potentiality of Curcumin and Conventional Drugs for CagA Oncoprotein Inactivation.

The oncoprotein cytotoxic associated gene A (CagA) of Helicobacter pylori plays a pivotal role in the development of gastric cancer, so it has been an important target for anti‐H. pylori drugs. Conventional drugs are currently being implemented against H. pylori. The inhibitory role of plant metabolites like curcumin against H. pylori is still a major scientific challenge. Curcumin may represent a novel promising drug against H. pylori infection without producing side effects. In the present study, a comparative analysis between curcumin and conventional drugs (clarithromycin, amoxicillin, pantoprazole, and metronidazole) was carried out using databases to investigate the potential of curcumin against H. pylori targeting the CagA oncoprotein. Curcumin was filtered using Lipinskis rule of five and the druglikeness property for evaluation of pharmacological properties. Subsequently, molecular docking was employed to determine the binding affinities of curcumin and conventional drugs to the CagA oncoprotein. According to the results obtained from FireDock, the binding energy of curcumin was higher than those of amoxicillin, pantoprazole, and metronidazole, except for clarithromycin, which had the highest binding energy. Accordingly, curcumin may become a promising lead compound against CagA+ H. pylori infection.

Epigenetic changes in carcinogenesis of gallbladder.

Gallbladder cancer (GBC) is a lethal and a common malignancy affecting mostly females. There are restricted high incidence pockets across the world and in northern India highest incidence of GBC is reported from the Gangetic belt. The etiology of this disease remains largely unknown though several risk factors have been stated. The genetic aberrations in GBC involving mutations in tumor suppressor genes and oncogenes have been reported in literature. However, there is scarcity of data regarding epigenetic changes that may also be involved in gallbladder carcinogenesis. This review attempts to summarize our current understanding of the epigenetic changes in GBC.

Heterogeneous expression of cholecystokinin and gastrin receptor in stomach and pancreatic cancer: An immunohistochemical study

AIM Cholecystokinin (CCK) and gastrin (Gs) are a well known trophic factor for the gastrointestinal tract and their trophic effects are shown mainly toward pancreas and stomach, respectively. Though, the exact characterization of CCK and Gs receptors subtype (cholecystokinin type A receptor [CCKAR] and cholecystokinin type B receptor/gastrin receptor [CCKBR/GR]) in stomach cancer (SC) and pancreatic cancer (PC) is still controversial and necessities further validation. SUBJECTS AND METHODS CCKAR and CCKBR/GR expression was analyzed by immunohistochemistry in 55 SC, 25 benign gastric diseases (BGDs), 38 PC (including periampullary carcinoma), and 10 normal pancreatic tissue. The results were statistically correlated with the patients clinical history to observe the prognostic significance if any. RESULT CCKAR expression was detected in 18.2% of SC, 20% of BGD, 65.8% of PC, and 30.0% of normal pancreas tissue samples. The CCKBR/GR expression was detected in 58.2% of SC, 48.0% of BGD, 18.4% of PC, and 60.0% of normal pancreas tissue samples. CCKBR/GR expression was significantly high in well and moderately differentiated SC samples as compared to poorly differentiated samples. CONCLUSION Our study showed significantly higher expression of CCKAR and down regulation of CCKBR in PC as compared to control while CCKBR/GR was detected in majority of SC samples. Thus, our study suggests that CCK and Gs receptors may have diagnostic and therapeutic implications. However, study need to be validated in significantly bigger sample size and need to be replicated in different cohorts.

Implication of Endophytic Metabolite and Their Derivatives in Cancer Chemotherapy: A Prospective Study

Incidence of cancer keep increasing worldwide may be due to genetic aberration, environmental effect, diet, socioeconomic factors, and various types of infections. Our previous studies revealed an association of Helicobacter pylori (H. pylori) and their species, Salmonella Typhi (S. Typhi), and Mycobacterium with various gastrointestinal tract (GI) cancers including oral, oropharyngeal, esophageal, gastric, gallbladder, pancreatic, and anal-canal cancers. We experience that poor cure rate is reported due to failure of conventional medicine, drug resistance, and failure to know the exact cause. As we are a group of oncologist and basic researcher, it is our experience that surgical procedures and chemotherapy are better adjuvant therapeutic option for cancer treatment. The area of chemotherapy is enhanced, but basic foundation is devised from natural products, which are used directly or as synthetic derivatives as stand-alone or in different combinations. Microorganisms, either bacteria or fungi that live inside plant tissue (endophytes) system, are big source of natural antimicrobial compound. It is known that endophytic alkaloids, taxoids, podophyllotoxins, etc., have an antineoplastic activity. Keeping these facts in mind, this chapter points out the active exploration and implication of endophytic metabolite and their derivatives in cancer chemotherapy in near future. Obtained data were analyzed and result showed that the endophytic metabolites may be potential source of newer cancer chemotherapeutic drugs. It concluded that in the field of cancer chemotherapy, search for novel drugs from endophytic origin is still a priority.

Nd:YAG laser therapy of carcinoma lip (stage I squamous cell carcinoma): a retrospective evaluation

ObjectiveTo asses the efficacy of Nd:YAG laser for stage I squamous cell carcinoma of the lip. To the authors’ knowledge this is the first reported study on this subject.Study designRetrospective study design involving treatment of 46 patients of either sex of stage I squamous cell carcinoma of lip over a 10-year period in a single tertiary care university teaching hospital with Nd:YAG laser.MethodsNd:YAG laser ablation of lesions in lip was carried out in all the patients on an OPD basis with prior consent. A regular follow-up was maintained for a period of 5 years. A negative biopsy at the end of one month and one year was considered a treated case. The tabulated data was analysed statistically by “Kaplan Meier” method and “Log Rank” test. Also cosmetic and functional results were assessed by any sign of flow away after filling the oral cavity with water and postoperative integrity of facial nerve in accordance with “House Brackmann” classification.ResultsIn this series of 46 patients, 35 patients were disease free at the end of 3 years and this number further declined to 29 at the end of 5 years with 4 deaths and 2 more patients lost to follow-up. The statistical evaluation by Kaplan Meier method gives us an overall 5-year survival rate of 88.14% with a mean survival of 58 months. Further 8 patients required repeat laserization either for residual or recurrence of lesion. Also 2 patients had a lymph node metastasis during the follow-up period. Thus, by applying Kaplan Meier method recurrence-free survival (RFS) and disease-free survival was found to be 85.1% (mean: 55 months) and 73.34% (mean: 57 months respectively. Interestingly on applying Log Rank test it was observed that the site of the lip involvement, i.e. whether upper or lower had no influence on disease-free survival. It was also observed that history of tobacco intake did not influence the disease free survival either (Log Rank Test). Moreover the cosmetic results were excellent and with no significant complication observed.ConclusionThe results reported here support the use of Nd:YAG laser for treatment of Stage I squamous cell carcinoma of lip in accordance with principles of minimal invasive and morbid surgery.