Anti-K-ras ribozyme induces growth inhibition and increased chemosensitivity in human colon cancer cells

Colon cancer is one of the carcinomas that is resistant to a variety of therapies. To develop a new therapy by regulating the activated K-ras gene in colon cancers, we prepared synthetic DNA encoding the ribozyme (catalytic RNA), and inserted it into an expression vector (LNCX) originated from a retrovirus. Transfection of the vector into SW620 human colon cancer cells brought about significant suppression of K-ras mRNA synthesis and inhibition of the cell growth. Studies in athymic mice, in which K-ras ribozyme-introduced SW620 cells were transplanted, also revealed a marked reduction of tumor growth in vivo. Furthermore, the ribozyme-introduced tumors became more sensitive to treatment with anti-cancer drugs such as cisplatin, adriamycin, 5-fluorouracil, vincristine, and etoposide. These data suggest that the possible efficacy of anti-K-ras ribozyme increases the chemosensitivity of human colon cancers as well as the inhibitory effect on the growth of human colon cancers.     

Postirradiation neoplasia: A symposium

It is impossible to prove that radiation given for benign conditions in infancy and childhood is an etiologic factor in the subsequent development of carcinoma in the head and neck area. Nevertheless, the suggestive evidence is quite impressive and the information from many sources correlates well. There are some conflicting reports but, in general, it can be said that very high doses of radiation are less likely to be carcinogenic than lesser amounts. Very small doses of radiation are probably not carcinogenic either. In general, the younger the patient at the time of exposure to radiation, the greater is the risk of subsequent development of carcinoma. The breast seems to be an exception, however, as it is more sensitive to radiation carcinogenesis between the ages of 10 and 35. Chronic low doses of radiation seem to be more carcinogenic in humans. The latent interval between irradiation and the appearance of carcinoma in most sites averages about 30 years; leukemia tends to occur 5–8 years after irradiation. The atomic bomb data are confusing. Up to 30% of the Hiroshima bomb radiation consisted of neutrons, whereas the neutron radiation of the Nagasaki bomb was very low. The higher incidence of breast cancer associated with the former type of irradiation may be related to the higher carcinogenicity of neutrons. On the other hand, the lower normal incidence of breast carcinoma in Japanese women may be a modifying factor of RBE of radiation in tumor induction.Irradiation for malignant tumors in all parts of the body, although an exceedingly valuable addition to the cancer therapy armamentarium, probably predisposes to the later development of irradiation carcinoma in the long-term survivors. This becomes increasingly important as more children and young adults with malignant tumors are clinically cured of their original malignant tumor with multimodal therapy including irradiation.The risk of carcinogenesis in radiation-treated patients never disappears. These patients should be followed carefully for life.     

Integrating hepatitis B prevention into sexually transmitted disease services: U.S. sexually transmitted disease program and clinic trends--1997 and 2001

OBJECTIVE: The objective of this study was to measure the progress since 1997 of implementing sexually transmitted disease (STD) clinic-based recommendations for hepatitis B prevention. GOAL: The goal of this study was to assess improvements since 1997 in hepatitis B prevention integration in STD services. STUDY: Repeating a 1997 survey, in 2001, a survey was sent to state, municipal, and territorial STD program managers, previously surveyed clinic managers, and a national sample of 500 STD clinics. RESULTS: Large increases were found in the percentage of clinics offering hepatitis B vaccine (from 61% to 82%), providing education (49% to 84%), and accessing federal vaccine programs (48% to 84%). Twice as many program managers considered all patients with STDs eligible for hepatitis B vaccination. Lack of resources and patient noncompliance with vaccine series completion were program barriers. CONCLUSIONS: Hepatitis B policies and vaccination and education efforts in STD clinics have improved; however, many barriers reported in 1997 remained in 2001.     

Specific reading disability (dyslexia): what have we learned in the past four decades?

We summarize some of the most important findings from research evaluating the hypothesized causes of specific reading disability ('dyslexia') over the past four decades. After outlining components of reading ability, we discuss manifest causes of reading difficulties, in terms of deficiencies in component reading skills that might lead to such difficulties. The evidence suggests that inadequate facility in word identification due, in most cases, to more basic deficits in alphabetic coding is the basic cause of difficulties in learning to read. We next discuss hypothesized deficiencies in reading-related cognitive abilities as underlying causes of deficiencies in component reading skills. The evidence in these areas suggests that, in most cases, phonological skills deficiencies associated with phonological coding deficits are the probable causes of the disorder rather than visual, semantic, or syntactic deficits, although reading difficulties in some children may be associated with general language deficits. Hypothesized deficits in general learning abilities (e.g., attention, association learning, cross-modal transfer etc.) and low-level sensory deficits have weak validity as causal factors in specific reading disability. These inferences are, by and large, supported by research evaluating the biological foundations of dyslexia. Finally, evidence is presented in support of the idea that many poor readers are impaired because of inadequate instruction or other experiential factors. This does not mean that biological factors are not relevant, because the brain and environment interact to produce the neural networks that support reading acquisition. We conclude with a discussion of the clinical implications of the research findings, focusing on the need for enhanced instruction.