Combining Neoplasms

Whatever mathematical model is assumed for the dose-incidence relationship, it is noteworthy that susceptibility can vary markedly with age, so that the radiation-induced cancer excess at various times after irradiation may more nearly approximate a constant percentage of the natural age-specific incidence than a constant number of additional cases, depending on the neoplasm in question. For some individual neoplasms, but not the leukemias, the data do in fact suggest that the "relative risk model is more appropriate than the absolute risk model (see Section 6.1.7). For all neoplasms combined, also, the excess of radiation-induced cases at different times after irradiation approximates more nearly a constant percentage of the age-specific incidence. 

Mucopolysaccharide levels are increased in many cancer cells this increase is accompanied by a decreased vascular supply. Hyaluronidase [9001-54-17, obtained from bovine testis, dissolves the mucopolysaccharides surrounding a tumor, thereby allowing cytotoxic agents to penetrate the neoplasm with enhanced faciUty. In clinical studies hyaluronidase was given to patients with malignant tumors, alone or in combination with 5- uorouracil [51-21-8], significant decreases in tumormass were observed (55). 

DNLM 1. Antineoplastic Agents, Combined—administration dos age—Handbooks. 2. Antineoplastic Agents, Combined—therapeutic use —Handbooks. 3. Neoplasms—drug therapy—Handbooks. QV 39 L276c 2001]... 

Chlordane interacts with other chemicals to produce additive or more-than-additive toxicity. For example, chlordane increased hepatotoxic effects of carbon tetrachloride in the rat (USEPA 1980 WHO 1984), and in combination with dimethylnitrosamine acts more than additively in producing liver neoplasms in mice (Williams and Numoto 1984). Chlordane in combination with either endrin, methoxychlor, or aldrin is additive or more-than-additive in toxicity to mice (Klaassen et al. 1986). Protein deficiency doubles the acute toxicity of chlordane to rats (WHO 1984). In contrast, chlordane exerts a protective effect against several organophosphorus and carbamate insecticides (WHO 1984), protects mouse embryos against influenza virus infection, and mouse newborns against oxazolone delayed hypersensitivity response (Barnett et al. 1985). More research seems warranted on interactions of chlordane with other agricultural chemicals. 

Gore, S.D. et al. (2006) Combined DNA methyltransferase and histone deacetylase inhibition in the treatment of myeloid neoplasms. Cancer Research, 66, 6361-6369. 

A recent study confirmed that ethylene thiourea was carcinogenic in male and female rats as shown by increased incidences of thyroid follicular cell neoplasms after treatment of up to 250 ppm in the diet for 2 years. In mice, concentrations ranging from 100 to 1000 ppm for 2 years caused liver and pituitary tumors in addition to thyroid tumors. Perinatal exposure up to 8 weeks followed by a control diet for 2 years was not carcinogenic in rats or mice. Combined perinatal-adult ETU exposures produced the same carcinogenic effects as adult-only exposures. 

Rats and mice exposed to 31, 63, or 12 5 ppm 6 hours/day for 16 days developed lesions in the nasal respiratory epithelium and/or olfactory epithelium, and the severity of the lesions generally increased with increasing exposure concentrations. Clinical findings included dyspnea, hypoactivity, and nasal and ocular discharge. At 250ppm all animals died within 4 days. In 2-year inhalation studies at doses of 2, 8, or 32 ppm rats and male mice had increased incidences of nonneoplastic lesions of the nose and increased severity of nephropathy female mice had increased incidences of nonneoplastic lesions of the nose and corneal degeneration. In addition, there was some evidence of carcinogenicity in male rats based on increased incidences of combined neoplasms of the nose and equivocal evidence... 

In male rats dosed by gavage at doses up to 60mg/kg, spontaneous seizures occurred at 12.5 mg/kg, the lowest dose used. Chronic oral studies in rats revealed no evidence of neoplasms, whereas one study in mice found an increased incidence of combined hepatocellular adenomas and carcinomas in females. It has been noted that these mmors in mice are poor predictors for malignancy in other species. A number of studies suggest that RDX is not mutagenic. ... 

Studies in rats reported renal tubular adenomas and adenocarcinomas in male and female animals at doses of 20 mg/kg/day (Kociba et al. 1977a). Metastasis to the lungs was observed. Combined incidences of renal tubular neoplasms in males (9/39, 23%) and in females (6/40, 15%) increased (p <0.05) over controls (males-1/90, females-0/90, 0%). The tumor incidence was not increased in the 0.2 and 2 mg/kg/day dose groups but there were some indications of hyperplasia in animals exposed to 2 m /kg/day. The EPA (1990f) evaluated these data and calculated a human potency factor of 7.8x10 (mg/kg/day) (qi ), representing 95% upper confidence limit of extra lifetime human risk. Based on this value, cancer risk levels of 10, 10, and 10 correspond to exposures of 0.001, 0.0001, 0.00001 mg/kg/day. 

DNLM 1. Neoplasms—drug therapy. 2. Neoplasms—radiotherapy. 3. Combined Modality Therapy. QZ 266... 

Pancreatic effect. Cigarette smoke, administered to anesthetized rats alone or in combination with iv ethanol infusion, reduced pancreatic blood flow temporarily and increased leukocyte-endothelium interaction (roller p < 0.001, sticker p < 0.01 vs baseline). Cigarette smoke potentiated the impairment of pancreatic capillary perfusion caused by ethanol, and both the number of rolling leukocytes and myeloperoxidase activity levels were increased compared with ethanol or nicotine administration alone h Tobacco-specific nitrosamines, administered to rats, induced pancreatic acinar cell and ductal cell neoplasms. One of the tumors had a mixed ductal-squamous-islet cell components . 

Sufficient evidence of carcinogenicity The Working Group considers that a causal relationship has been established between the agent or mixture and an increased incidence of malignant neoplasms or of an appropriate combination of benign and malignant neoplasms in (a) two or more species of animals or (b) in two or more independent studies in one species carried out at different times or in different laboratories or under different protocols. 

A major breakthrough in the treatment of lymphoid malignancies was the discovery of monoclonal antibody activity, especially that of rituximab. Rituximab was the first monoclonal antibody approved by the U.S., FDA for the treatment of relapsed follicular lymphoma (1), and it has now been extensively used for the treatment of various lymphoid neoplasm which express CD20 antigen. Its efficacy has been also demonstrated against diffuse large B-cell lymphoma when administered as a combination regimen such as rituximab plus CHOP (R-CHOP) chemotherapy (2). 

---