Expression of a novel endothelial marker, C-type lectin 14A, in epithelial ovarian cancer and its prognostic significance.

OBJECTIVE: The purpose of this study was to evaluate microvessel density (MVD) as assessed by C-type lectin 14A (CLEC14A), which is a new marker for endothelial cells, and compare its expression to CD31 and CD105 in epithelial ovarian cancer (EOC). METHODS: MVD was evaluated in tumors (n = 50) from patients with EOC who underwent primary surgery and in patients with EOC who received preoperative chemotherapy (n = 49) using immunohistochemistry with antibodies to CLEC14A, CD31 and CD105. The median duration of follow-up was 24.5 months (range 1-101 months). The effect of prognostic factors on event-free survival (EFS) and overall survival (OS) was assessed using the Cox regression model. RESULTS: The amount of residual disease was found to be an independent prognostic factor in multivariate analysis with respect to EFS (P = 0.009) and OS (P < 0.001). The mean MVD of CLEC14A (MVD = 6), in tumors from patients who underwent primary surgery, was significantly lower than that of CD31 (MVD = 25, P < 0.0001) and CD105 (MVD = 11, P = 0.018). However, there was no significant correlation between MVD as detected by these markers and clinical outcome. There was no expression of CLEC14A in tumors from patients who received preoperative chemotherapy and the MVD of CD31 and CD105 was significantly reduced (P = 0.001 and 0.006, respectively) in this set of patients. CONCLUSION: This study demonstrates MVD as detected by CLEC14A in EOC. Treatment with chemotherapy reduces tumor blood vessels significantly. We suggest that CLEC14A may be a more specific endothelial marker to assess tumor angiogenesis.

Mn-doped zinc sulphide nanocrystals for immunofluorescent labeling of epidermal growth factor receptors on cells and clinical tumor tissues.

The field of molecular detection and targeted imaging has evolved considerably with the introduction of fluorescent semiconductor nanocrystals. Manganese-doped zinc sulphide nanocrystals (ZnS:Mn NCs), which are widely used in electroluminescent displays, have been explored for the first time for direct immunofluorescent (IF) labeling of clinical tumor tissues. ZnS:Mn NCs developed through a facile wet chemistry route were capped using amino acid cysteine, conjugated to streptavidin and thereafter coupled to biotinylated epidermal growth factor receptor (EGFR) antibody utilizing the streptavidin-biotin linkage. The overall conjugation yielded stable EGFR antibody conjugated ZnS:Mn NCs (EGFR ZnS:Mn NCs) with a hydrodynamic diameter of 65 ± 15 nm, and having an intense orange-red fluorescence emission at 598 nm. Specific labeling of EGF receptors on EGFR(+ve) A431 cells in a co-culture with EGFR(-ve) NIH3T3 cells was demonstrated using these nanoprobes. The primary antibody conjugated fluorescent NCs could also clearly delineate EGFR over-expressing cells on clinical tumor tissues processed by formalin fixation as well as cryopreservation with a specificity of 86% and accuracy of 88%, in comparison to immunohistochemistry. Tumor tissues labeled with EGFR ZnS:Mn NCs showed good fluorescence emission when imaged after storage even at 15 months. Thus, ZnS nanobioconjugates with dopant-dependent and stable fluorescence emission show promise as an efficient, target-specific fluorophore that would enable long term IF labeling of any antigen of interest on clinical tissues.

A pilot study to assess the feasibility of evaluation of markers of response to chemotherapy at one day & 21 days after first cycle of chemotherapy in carcinoma of breast: a prospective non-randomized observational study.

BACKGROUND: Interest in translational studies aimed at investigating biologic markers in predicting response to primary chemotherapy (PCT) in breast cancer has progressively increased. We conducted a pilot study to evaluate feasibility of evaluating biomarkers of response to PCT at one & 21 days after first cycle. METHODS: Adult, non-pregnant, non-lactating women with histologically confirmed infiltrating duct carcinoma underwent serial core biopsies after first cycle of PCT and these were scored for Ki-67, Bcl-2 and Caspase-3 using immunohistochemistry. RESULTS: We recruited 30 patients with a mean age of 51 years. We were successful 95.6% times in performing a core biopsy and of these 84.6% had adequate tissue in the cores harvested. After a mean of 4 cycles of PCT, 26 patients underwent surgery and good response was noted in 9 patients (30%) using Miller-Payne criteria. There was a trend noted in all markers, which appeared different in those with good response and poor response. Good responders had significantly higher Ki-67 and significantly lower Bcl-2 at baseline and a significant decrease in Ki-67 and Caspase-3 at 21 days after the first chemotherapy. CONCLUSION: We report a detectable change in biomarkers as early as 24-48 hours after the first chemotherapy along with a definite trend in change that can possibly be used to predict response to chemotherapy in an individual patient. The statistical significance and clinical utility of such changes needs to be evaluated and confirmed in larger trials.

Sly Disease: Mucopolysaccharidosis Type VII.

A 6 month-old infant presenting with severe mitral regurgitation was found to have hepatosplenomegaly, corneal clouding, and Alder-Reilly granules in the leucocytes. Extremely low levels of beta glucuronidase confirmed the diagnosis of Sly disease (Mucopolysaccharidosis VII). This is the first case of MPS VII reported from India.

Oxidative stress is the primary event: Effects of ethanol consumption in brain.

Damaging effects of reactive oxygen species on living systems are well documented. They include oxidative attack on vital cell constituents. Chronic ethanol administration is able to induce an oxidative stress in the central nervous system. In the present study, 16-18 week-old male albino rats of Wistar strain were exposed to different concentration of ethanol for 4 weeks. This exposure showed profound effect on body weight. Ascorbic acid level; and activities of alkaline phosphatase and aspartate transaminase in the brain are dependent on the concentration of ethanol exposure. Chronic ethanol ingestion elicits statistically significant increase in thiobarbituric acid reactive substances level and decrease in gluatathione level in the brain. It reduces superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase activities in a dose dependent manner. However, histological examination could not reveal any pathophysiological changes. Therefore, we conclude that biochemical alterations and oxidative stress related parameters respond early in alcoholism than the histopathological changes in brain.

Acute myeloid leukemia presenting as obstructive jaundice.

We report a 32-year-old man with acute myeloid leukemia presenting as obstructive jaundice. Imaging revealed dilated common bile duct with abrupt narrowing at the lower end, distended gall bladder, and dilated intrahepatic biliary radicles. In addition he had a mass lesion in the urinary bladder. On evaluation he was found to have the eosinophilic variant of M4 subtype acute myeloid leukemia. He expired before chemotherapy could be instituted.

Esthesioneuroblastoma with intracranial extension: A non-surgical approach.

Esthesioneuroblastoma is a rare tumor arising from the olfactory mucosa of upper respiratory tract. The primary modality of treatment has been surgery with craniofacial resection followed by post-operative radiotherapy. There are only a few reported cases of non-surgical approaches. We report a case of esthesioneuroblastoma with intracranial extension treated with Vincristine, Adriamycin, Cyclophosphamide, Ifosfamide, Etoposide protocol followed by radiation with 5 years of follow-up. This is the first reported case using this chemotherapy schedule.

The Churg-Strauss syndrome: An unusual presentation.

The Churg-strauss syndrome (CSS), also referred to as allergic angiitis and granulomatosis is characterized by asthma, peripheral and tissue eosinophilia, extravascular granuloma formation, and vasculitis of multiple organ systems. It is an uncommon disease with an estimated annual incidence of 1-3 per million. Here, we report a case of CSS with glomerulocentric granulomatous reaction with interstitial eosinophils and involvement of retinal vessels.

Primary transitional cell carcinoma of the fallopian tube in a premenopausal woman: A case report and review of literature.

Transitional carcinomas are extremely rare in the fallopian tube. A 41-year-old premenopausal lady presented with colicky abdominal pain and was found to have a left-sided pelvic mass on examination. In view of the elevated CA-125 and imaging findings suggestive of ovarian mass, she underwent staging laparotomy. Pathological examination confirmed a primary transitional cell carcinoma of the left fallopian tube. Review of available literature suggested that the primary transitional cell carcinoma is probably less aggressive compared to classical adenocarcinoma of the fallopian tube, and it has to be distinguished from the recently recognized entity, parafallopian tube transitional cell carcinoma.