Expression of oncofoetal marker carcinoembryonic antigen in oral cancers in South India--a pilot study

Expression of the oncofoetal glycoprotein, carcinoembryonic antigen (CEA), has been observed in a number of malignancies and is also being pursued as a target for anti-cancer therapy. This study explored the status of this biochemical entity in the oral squamous cell carcinoma (SCC) in South India caused by extensive chewing habits. Squamous cell carcinoma in the study belonged to grade I and grade II. Tumour staging of the patients recruited in the study ranged from T2N1M0 to T4N3M0. Of the grade II cases studied, 88% (7 out of 8) showed expression of CEA. The 2 cases of grade I SCC of buccal mucosa also showed positive anti-CEA staining. If the results from this pilot study can be validated with a larger sample size, a role can be attributed to this tumour marker in oral neoplasia, thereby opening up avenues for using CEA as an additional diagnostic marker in oral SCC in this population and as a possible target for anti-cancer therapy.     

The effects of peptides on tolerance to the cataleptic and hypothermic effects of morphine in the rat

The effects of melanotropin release inhibiting factor (MIF) and a cyclic analog, cycio (Leu-Gly) derived from MIF on the development of tolerance to the cataleptic and hypothermic effects of morphine in the rat were investigated. The rats were made tolerant to morphine by the subcutaneous implantation of four morphine pellets over a 3-day period. Each pellet contained 75 mg of morphine-free base. Following morphine pellet implantation, tolerance developed to the cataleptic and hypothermic effects of morphine. A dose of morphine (50 mg/kg) which produced hypothermia in placebo-pelleted rats, produced hyperthermia in morphine-pelleted rats. Administration of MIF and cycio (Leu-Gly) prior to and during morphine pellet implantation inhibited the development of tolerance to the cataleptic effect of morphine. Similarly the hyperthermic effect of morphine in morphine-tolerant rats was prevented by both the peptides. Previously, the present authors reported Ithat these peptides also inhibited tolerance to the analgesic effect of morphine. It is concluded that tolerance to analgesic, cataleptic and hypothermic effects of morphine may share common features in its genesis.     

The synthesis rate and turnover time of 5-hydroxy-tryptamine in brains of rats treated chronically with morphine.

1. Four schedules of subcutaneous pellet implantation were used to induce tolerance to and physical dependence on morphine in Sprague-Dawley rats. 2. The schedules included implantation of four morphine pellets (each containing 75 mg of morphine free base) during a 3 day period (schedule 1); six pellets during 3 days (schedule 2); six pellets during 7 days (schedule 3) and ten pellets during a 10 day period (schedule 4). 3. A high degree of tolerance and dependence on morphine, comparable to that induced in mouse by implantation of a single morphine pellet for 3 days, was produced with schedule 4. 4. Brain 5-hydroxytryptamine (5-HT) turnover rates as measured by rate of accumulation of 5-HT after monoamine oxidase inhibition by pargyline were not different in rats rendered tolerant to and dependent on morphine according to schedules 1 to 4 when compared with corresponding placebo pellet-implanted rats. 5. The turnover rates of 5-HT in brain of morphine-and placebo pellet-implanted rats (schedule 4) from which the pellets had been removed for 24 h were also similar. 6. It is concluded that tolerance to, and physical dependence upon morphine in the rat is not associated with changes in brain 5-HT dynamics.     

The acute effects of cigarette smoking on left ventricular function

Cigarette smoking is a major risk factor of coronary artery disease. Frequent repetition of an acute effect on the heart caused by cigarette smoking has been suggested as the etiology because of the increased incidence of myocardial infarction in cigarette smokers which drops to the incidence in non-smokers after cessation of smoking. This study of cardiac patients during cardiac catheterization evaluates the acute effect of the ordinary cigarette, smoked in the individuals own manner, on parameters of cardiac pump and muscle performance. The accuracy of measurements was enhanced by employing high-fidelity pressure signals, signal averaging, and computer analysis of the data. The results of the present study suggest that when cardiac patients smoke 1 cigarette of their own brand in their accustomed manner, no deleterious effects on pump performance, ventricular contraction or relaxation and blood pressure are evident.     

Glycolytic rate and lymphomagenesis depend on PARP14, an ADP ribosyltransferase of the B aggressive lymphoma (BAL) family

Poly(ADP-ribose)polymerase (PARP)14--a member of the B aggressive lymphoma (BAL) family of macrodomain-containing PARPs--is an ADP ribosyltransferase that interacts with Stat6, enhances induction of certain genes by IL-4, and is expressed in B lymphocytes. We now show that IL-4 enhancement of glycolysis in B cells requires PARP14 and that this process is central to a role of PARP14 in IL-4-induced survival. Thus, enhancements of AMP-activated protein kinase activity restored both IL-4-induced glycolytic activity in Parp14(-/-) B cells and prosurvival signaling by this cytokine. Suppression of apoptosis is central to B-lymphoid oncogenesis, and elevated macro-PARP expression has been correlated with lymphoma aggressiveness. Strikingly, PARP14 deficiency delayed B lymphomagenesis and reversed the block to B-cell maturation driven by the Myc oncogene. Collectively, these findings reveal links between a mammalian ADP ribosyltransferase, cytokine-regulated metabolic activity, and apoptosis; show that PARP14 influences Myc-induced oncogenesis; and suggest that the PARP14-dependent capacity to increase cellular metabolic rates may be an important determinant of lymphoma pathobiology.     

Stem cell--is there any role in tumorigenic activity

Stem cells are a quintessential key to proper behavior of homeostatic processes. They are often thought of as the solution to a wide range of human conditions, with the ability to rescue malfunctioning or non-functioning organs and tissues. However, there is increasing evidence that stem cells can play a central role in disease. Most recently stem cells have been implicated in cancer after not responding to homeostasic controls such as proliferation and differentiation. Cancer has long been seen as a disease that arises from mutations that impair the capacity of any cell within the organism to respond to the signals that regulate proliferation. Besides their scarcity or abundance, a second important issue with respect to cancer stem cells is their origin. A new defining model for carcinogenesis, the "cancer stem cell hypothesis" was put forward in 2006, according to which cancer is a stem cell disease that places malignant stem cells at the centre of its tumorigenic activity as they have the capacity to undergo self-renewal, and have the potential to differentiate into different types of cells in a specific lineage.     

Cytomegalovirus infection as a cause of cytopenia after chemotherapy for hematological malignancies

Objective

Unlike hematopoietic stem cell transplantation, there is very little information on cytomegalovirus (CMV) related cytopenias occurring in patients having acute lymphoblastic leukemia (ALL) or Non Hodgkin’s lymphoma (NHL) receiving standard dose chemotherapy (SDCT). We studied the role of CMV infection in cytopenias after SDCT for childhood ALL or NHL.

Design

Retrospective study.

Setting

Pediatric Oncology Unit.

Methods

Between January 2007 and March 2010, we screened all children having ALL/ NHL having prolonged cytopenia (ANC<1,000/cmm and/or platelets <1,00,000/cmm; >10 days beyond date for next chemotherapy; not explainable on basis of previously administered chemotherapy) for CMV infection. Testing for CMV infection was done by pp65 antigen assay, qualitative or quantitative RT-PCR. CMV positive episodes were analyzed for relationship to previous chemotherapy, clinical features and response to treatment.

Results

As defined, 24 episodes of cytopenia were identified. CMV infection was detected in 13/24 (54%) episodes in 9 patients. Duration of cytopenia in patients having CMV infection: 14–126 days (median 28 d). Neutropenia or thrombocytopenia were seen in 11/13 and 13/13 episodes, respectively. Fever (2–20 d) and loose motions (3–60 d) in 11/13 and 9/13 episodes, respectively. Eye examination records were available in 5 children; 3 had simultaneous or delayed chorioretinitis. Gancyclovir was used in all but 1 CMV-positive episode. In treated cases, counts recovered after a median of 8 days (3–56 d).

Conclusion

Following chemotherapy for ALL/NHL, cytopenia that is prolonged or not explainable on the basis of chemotherapy toxicity should be evaluated for CMV infection.