Mohan Kumar

Layered double hydroxides as effective carrier for anticancer drugs and tailoring of release rate through interlayer anions

Hydrophobic anticancer drug, raloxifene hydrochloride (RH) is intercalated into a series of magnesium aluminum layered double hydroxides (LDHs) with various charge density anions through ion exchange technique for controlled drug delivery. The particle nature of the LDH in presence of drug is determined through electron microscopy and surface morphology. The release of drug from the RH intercalated LDHs was made very fast or sustained by altering the exchangeable anions followed by the modified Freundlich and parabolic diffusion models. The drug release rate is explained from the interactions between the drug and LDHs along with order-disorder structure of drug intercalated LDHs. Nitrate bound LDH exhibits greater interaction with drug and sustained drug delivery against the loosely interacted phosphate bound LDH-drug, which shows fast release. Cell viability through MTT assay suggests drug intercalated LDHs as better drug delivery vehicle for cancer cell line against poor bioavailability of the pure drug. In vivo study with mice indicates the differential tumor healing which becomes fast for greater drug release system but the body weight index clearly hints at damaged organ in the case of fast release system. Histopathological experiment confirms the damaged liver of the mice treated either with pure drug or phosphate bound LDH-drug, fast release system, vis-à-vis normal liver cell morphology for sluggish drug release system with steady healing rate of tumor. These observations clearly demonstrate that nitrate bound LDH nanoparticle is a potential drug delivery vehicle for anticancer drugs without any side effect.

Toxicology and free radicals scavenging property of Tamra bhasma

Free radicals are implicated in various chronic diseases. There has always been a search for new antioxidants. In this paper we have investigated Tamra bhasma, a metallic ayurvedic preparation. It is a time-tested medicine in Ayurveda and is in clinical use for various ailments specifically the free radical mediated diseases. Our results show that Tamra bhasma inhibits lipid peroxidation (LPO), prevents the rate of aerial oxidation of reduced glutathione (GSH) content and induces the activity of superoxide dismutase (SOD) in rat liver homogenate in the bi-phasic manner. The drug was orally given for 7, 15 and 30 days in different doses. Best protective response was found at the dose of 0.5mg/100g body weight in albino rats, although it showed some histopathological changes at the dose of 20mg/100g body weight. The results suggest that this Ayurvedic preparation is not merely a source of copper metal, but it is a strong anti-oxidant with no detectable adverse effect in lower doses of therapeutic range.

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.

Mucosal IgA & IL-1β in Helicobacter pylori Infection.

Helicobacter pylori infection stimulates strong local inflammatory and specific IgA antibody production. The influence of antibodies on the bacterial colonization is not clear. Here, we have analysed the association between the mucosal IgA level and IL-1β in various manifestations of the infection seen endoscopically. Antral biopsies of 57 dyspeptic patients were taken for culture, histology and estimation of mucosal levels of anti-H. pylori IgA and IL-1β. Mean mucosal IgA level was higher in patients with normal mucosa compared to all other groups and lower IgA level was associated with higher bacterial density. IL-1β was higher in ulcer patients and suspicious malignancy group as compared to normal group and higher level of IL-1β was associated with higher grades of metaplasia. Present study indicates that local immunity seems to have a protective role against H. pylori infection and higher level of IL-1β induced by the pathogen may be associated with metaplasia and carcinogenesis.

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.

Rhabdomyosarcoma of Biliary Tract— a Diagnostic Dilemma

Rhabdomyosarcoma is a soft tissue malignant musculoskeletal tumor. It is a rare tumor in children but the most common cause of malignant obstructive jaundice in them. A 4-year-old child presented to us with obstructive jaundice and palpable liver. He was misdiagnosed as choledochal cyst on imaging studies; however, intraoperative and histopathological features confirmed the diagnosis of rhabdomyosarcoma. Mass excision and Roux en Y portoenterostomy was performed. Post operatively; the patient was put on multimodal chemotherapy. This, being an uncommon entity, is being reported with a review of the available literature.

Cyclin D1 and cyclin E2 are differentially expressed in gastric cancer.

Cell cycle regulators cyclin D1 and cyclin E2 function in G1/S transition by activating downstream cyclin-dependent kinases. Deregulated expression of these cyclins has been reported in various cancers. However, little is known about their clinical significance in gastric carcinoma. We aimed to explore that whether there is differential expression of these cyclins in clinically distinct gastric cancer patients. In this study we recruited a total of 92 subjects including 20 controls and 72 cases of histopathologically proven gastric carcinoma. Expression profiling at transcript level was done by semiquantitative RT-PCR and of protein by immunohistochemistry. Receiver operator characteristics analysis was done for determining diagnostic utility of cyclin D1 and cyclin E2. We demonstrate that cyclins D1 and E2 are frequently overexpressed in early stages of gastric carcinoma. Interestingly, expression of cyclins D1 and E2 significantly correlates with different clinical parameters such as gender, histological type (intestinal and diffuse), tumor location (proximal, middle, and distal), tumor differentiation (differentiated and undifferentiated), tumor invasion (serosal, lymphatic, and venous) and tumor metastasis (lymph node, peritoneal, ascites, and liver). Cyclin D1 has significantly higher sensitivity and specificity as diagnostic biomarker than cyclin E2. Our results suggest that overexpression of cyclin D1 and cyclin E2 is an early event in gastric carcinogenesis. The differential expression of these cyclins may be useful as diagnostic biomarkers for early detection of gastric carcinoma.

Isolated intrathyroidal neurofibroma.

Neurofibroma is a benign tumor arising from a cutaneous or peripheral nerve. This tumor occurs sporadically or is associated with neurofibromatosis. Neurofibromas mainly occur on the trunk and extremities but may also be found in the head and neck region. Cosmesis is the major concern in these cases. This tumor rarely arises from the thyroid gland, but when that occurs, the tumor is commonly associated with neurofibromatosis. The isolated neurofibroma of the thyroid is extremely rare: only one case each of primary neurofibroma of the thyroid, neurofibroma of the thyroid capsule and a case of schwannoma have been reported previously. A 55-year-old female presented to us with an anterior neck swelling. There were no symptoms suggestive of hypoor hyperthyroidism or pressure symptoms. There were no other swellings on the body. Neck examination showed enlargement of the left lobe of the thyroid accompanied by deviation of the trachea with a few subcentimeter lymph nodes at level III. Thyroid hormone level was normal. CT scan of the neck showed a thyroid mass of 6 5 cm arising from the left lobe, causing deviation of the trachea to the right and anteriorly, and the presence of a few neck nodes (Fig 1). Fine-needle aspiration cytology showed colloid material, suggestive of colloid goiter. The patient was subjected to total thyroidectomy with removal of the lymph nodes (berry picking). Postoperative gross examination of the resected section showed replacement of the entire thyroid gland by a yellowish grey lobulated mass measuring about 5.5 5 cm in diameter. A small amount of normal thyroid tissue was also seen. Histopathological examination showed a tumor composed of spindle cells (Fig 2) and a diagnosis of neurofibroma was made. Five lymph nodes that were isolated showed reactive hyperplasia. The postoperative period was uneventful and the patient made an uneventful recovery. The patient is on follow-up without any specific complaints for the last 8 months. Written consent of the patient was obtained for publication of this case report.