Experimental studies of tumor radioimmunodetection using antibody mixtures against carcinoembryonic antigen (CEA) and colon-specific antigen-p (CSAp)

Experiments with the GW-39 human colonic carcinoma growing in hamsters showed that injection of radioactive antibody to a colorectal-specific, tumor-associated antigen, CSAp, results in better tumor radiolocalization than was seen previously with radioantibodies to carcinoembryonic antigen (CEA). However, a mixture of both radioactive antibodies resulted in potentiation of CEA-tumor radioimmunodetection without affecting CSAp-tumor radiolocalization. Hence, multi-marker antibody mixtures may be the method of choice in cancer radioimmunodetection.     

Xeroderma Pigmentosum

Five cases of xeroderma pigmentosum have been presented, three of the patients belonging to one family. There was no history of consanguineous marriages in this series. All five patients had advanced ocular complications. Three presented with multiple basal cell carcinomata, which were treated by radiotherapy in two cases and surgery in one. One patient presented with a dermatofibroma, which does not seem to have been reported earlier in association with this disease. Reconstructive techniques such as the use of flaps and grafts arc safe, and the healing response is quite satisfactory.     

Mitomycin and fluorouracil in combination with concomitant radiotherapy: a potentially curable approach for locally advanced head and neck squamous cell carcinoma

OBJECTIVE: The purpose of this study was to evaluate the efficacy of radiotherapy and concurrent mitomycin-C (MC) plus 5-fluorouracil (5FU) infusion in locally advanced squamous cell carcinoma of the head and neck (SCCHN). METHODS: Sixty-nine patients with SCCHN (6 Stage III and 63 Stage IV patients) were treated with external beam radiotherapy (70 Gy) and simultaneous intravenous chemotherapy with 5FU (600 mg/m(2)/day, Days 1-5) and MC (10 mg/m(2), Days 5 and 36). RESULTS: After a mean follow-up of 28.5 months, 59.4% of patients were alive without disease. Complete response was seen in 76.8% of patients. The 3 years overall survival, locoregional relapse-free survival and disease-free survival was 62.3, 63.1[corrected] and 49.5%, respectively. Treatment was well tolerated (Grade III mucositis in 43.5% and Grade II leukopenia in 5.8%). CONCLUSIONS: This concurrent chemoradiotherapy regimen offers a curative option for our patients where primary and nodal disease is fairly large resulting in hypoxic radioresistant tumors.     

Chondrosarcoma of the scapula: long-term oncologic outcome

BACKGROUND: Chondrosarcoma is the second most common primary sarcoma of bone. It often develops within flat bones, such as the pelvis, ribs, and scapula. In the current study, the authors reviewed the surgical experience and long-term oncologic outcomes of patients with chondrosarcoma arising in the scapula. METHODS: The medical records of 29 consecutive patients with chondrosarcoma of the scapula were reviewed. The patients were treated between 1954 and 1994. All patients had localized disease at the time of presentation. The tumors were classified histologically as Grade 1 (10 patients), Grade 2 (10 patients), Grade 3 (7 patients), dedifferentiated (1 patient), and mesenchymal (1 patient) (using the criteria of Evans et al.). The mean maximal dimension of the tumors was 11 cm. Twenty-five patients underwent limb-sparing surgical resection and 4 patients underwent forequarter amputations. The median follow-up was 13 years (range, 1-35 years). RESULTS: At last follow-up, 22 patients (76%) were free of disease and 7 patients (24%) had died of their disease. Local recurrence occurred in 4 patients at 7 months, 16 months, 40 months, and 43 months, respectively. The local recurrence-free survival rate was 86% at 5 years, 10 years, and 20 years. Disease-specific survival was 83% at 5 years, 74% at 10 years, and 74% at 20 years. Patients who had low-grade chondrosarcomas had better survival compared with patients who had high-grade chondrosarcomas (P = 0.07). CONCLUSIONS: Patients who had localized chondrosarcoma of the scapula had a favorable long-term outcome, most likely due to the unique anatomic features that improved the likelihood of achieving wide surgical margins with limb-sparing surgery, despite the frequent presentation of locally advanced disease.     

Progress in malaria vector control

Malaria control, except in tropical Africa, will probably continue to be based to a large extent on the use of insecticides for many years. However, the development of resistance to insecticides in the vectors has caused serious difficulties and it is necessary to change the strategy of insecticide use to maximize their efficacy. A thorough knowledge of the ecology and behaviour of each vector species is required before the control strategy can be adapted to different epidemiological situations. The behavioural differences between sibling species have been recognized for several years, but study of this problem has recently been simplified by improved means of identification that involve chromosomal banding patterns and electrophoretic analysis. Behavioural differences have also been associated with certain chromosomal rearrangements.     

Cyclin-dependent kinase 5 increases perikaryal neurofilament phosphorylation and inhibits neurofilament axonal transport in response to oxidative stress

Cyclin-dependent kinase 5 (cdk5) phosphorylates the high molecular weight neurofilament (NF) protein. Overexpression of cdk5 inhibits NF axonal transport and induces perikaryal accumulation of disordered phospho-NF cables. Experimental and clinical motor neuron disease is characterized by oxidative stress, increased cdk5 activity, and accumulation of phospho-NFs within perikarya or proximal axons. Because oxidative stress increases cdk5 activity in experimental motor neuron disease, we examined whether oxidative stress induced cdk5-mediated NF phosphorylation. Treatment of cultured neuronal cells with hydrogen peroxide inhibited axonal transport of green fluorescent protein-tagged NF subunits and induced perikaryal accumulation of NF phosphoepitopes normally confined to axons. These effects were prevented by treatment with the cdk5 inhibitor roscovitine or transfection with a construct expressing the endogenous cdk5 inhibitor peptide. These findings indicate that oxidative stress can compromise NF dynamics via hyperactivation of cdk5 and suggest that antioxidants may alleviate multiple aspects of neuropathology in motor neuron disease.     

Role of the Otx1 gene in cell differentiation of mammalian cortex

This study analyses by immunohistochemical methods the effects of the deletion of the Otx1 gene on 12 areas of the cerebral cortex and on neurons expressing Ca-binding proteins (CaBP), such as parvalbumin (Pv) and calbindin-D28K (Cb). We found that the deletion of the Otx1 gene modified differently the various cortical areas. The decrease in cortical thickness ranged from 29.35 to 9.85% and the reduction in cellular population from 35.90 to 3.65% in the different cortical areas. The influence of the Otx1 gene concerns all cortical layers with variable effects on different cortical areas. The cellular population of cerebral cortex considered as a whole was reduced by 20.67%, Pv-positive (Pv+) cells by 58.01% and Cb-positive (Cb+) cells by 51.54%. The quantitative distribution of Pv+ and Cb+ cells varied independently in the different cortical areas. Topographic analysis of CaBP cells in Otx1-null mice (Otx1(-/-)) showed that Pv+ cells were principally distributed in layers IV and V and Cb+ cells in layers V and VI. Given that in the development of wild-type mice both cell types first appear in deep layers and later spread to superficial ones, the segregation of CaBP neurons in inner layers of Otx1(-/-) animals is an index of the immaturity of the cerebral cortex of these animals. This study showed that the Otx1 gene has a more complex role than previously reported, as it is involved in the maturation and differentiation of various cerebral cortices, and, specifically, in the development of CaBP cells.     

Therapeutic potential of monoisoamyl and monomethyl esters of meso 2,3-dimercaptosuccinic acid in gallium arsenide intoxicated rats

The dose dependent effects of monoisoamyl and monomethyl esters of meso 2,3-dimercaptosuccinic acid (DMSA) (0.1, 0.3 and 0.5 mmol kg(-1), intraperitoneally (i.p.) once daily for 5 days) to offset the characteristic biochemical, immunological, oxidative stress consequences and DNA damage (based on DNA fragmentation and comet assay) following sub-chronic administration of gallium arsenide and the mobilization of gallium and arsenic were examined. The effects of these chelators alone in normal animals too were examined on above-mentioned variables. Male Wistar rats were exposed to 10 mg kg(-1), GaAs, orally once daily for 12 weeks and were administered DMSA or two of its monoesters (monoisoamyl or monomethyl) for 5 consecutive days. DMSA was used as a positive control. DMSA and its derivatives, when given alone, generally have no adverse effects on various parameters. After 5 days of chelation therapy in GaAs pre-exposed rats, MiADMSA was most effective in the reduction of inhibited blood delta-aminolevulinic acid dehydratase (ALAD) activity and zinc protoporphyrin level while, all three chelators effectively reduced urinary ALA excretion, compared to GaAs alone exposed rats. MiADMSA was also effective, particularly at a dose of 0.3 mmol kg(-1), in enhancing the inhibited hepatic transaminase activities. Parameters indicative of oxidative stress responded less favorably to the chelation therapy, however, three chelators significantly restored the altered immunological variables. MiADMSA was relatively more effective than the other two chelators. GaAs produced significant DNA damage in the liver and kidneys and the chelation treatment had moderate but significant influence in reducing DNA damage. All three chelators significantly reduced arsenic concentration and, however, MiADMSA was more effective than the other two chelators in depleting arsenic concentration from blood and other soft tissues. A dose of 0.3 mmol kg(-1) was found to be relatively better than the other two doses examined. Gallium contents of blood and soft tissues remained uninfluenced by the chelation therapy. Significant loss of copper after MiADMSA administration, however, is of concern and requires further exploration. Additionally, further studies are required for the choice of appropriate dose, duration of treatment and possible toxic/side effects. Keeping in view the promising role of MiADMSA in the treatment of GaAs poisoning, these data will be needed for the registration of this chelating agent as licensed drug for the treatment of gallium arsenide intoxication.     

Male reproductive toxicity of sodium arsenite in mice

The effect of chronic oral exposure to arsenic on male mouse testicular and accessory sex organ weights, sperm parameters and testicular marker enzymes was studied. In addition, the distribution of arsenic in reproductive organs was measured using atomic absorption spectrophotometry. Sodium arsenite administered to mice (Mus musculus) via drinking water at a dose of 53.39 micromol/L (4 ppm As) for 365 days caused a decrease in the absolute and relative testicular weight. However, epididymal and accessory sex organ weight was similar to control. The activities of marker testicular enzymes such as sorbitol dehydrogenase, acid phosphatase and 17beta-hydroxy-steroid dehydrogenase (17beta-HSD) were significantly decreased, but those of lactate dehydrogenase and gamma-glutamyl transpeptidase (gamma-GT) were significantly increased. A decrease in sperm count and sperm motility, along with an increase in abnormal sperm, was observed in arsenite-exposed mice. A significant accumulation of arsenic in testes, epididymis, seminal vesicle and prostate gland was observed in treated animals. Thus long term exposure (365 days) at the dose level of 53.39 micromol/L sodium arsenite (4 ppm As), to which human beings are likely to be exposed via drinking water, may cause testicular and spermatotoxic effect.