Pathogenetic role and clinical significance of interleukin-1β in cancer

In recent years, pro-oncogenic mechanisms of the tumour microenvironment (ТМЕ) have been actively discussed. One of the main cytokines of the TМЕ is interleukin-1 beta (IL-1β), which exhibits proinflammatory properties. Some studies have shown an association between an increase in IL-1β levels and tumour progression. The purpose of this review is to analyse the pathogenic mechanisms induced by IL-1β in the TМЕ, as well as the diagnostic significance of the presence of IL-1β in patients with cancer and the efficacy of treatment with IL-1β inhibitors. According to the literature, IL-1β can induce an increase in tumour angiogenesis due to its effects on the differentiation of epithelial cells, pro-angiogenic molecule secretion and expression of adhesion molecules, thus increasing tumour growth and metastasis. IL-1β is also involved in the suppression of anti-tumour immune responses. The expression and secretion of IL-1β has been noted in various types of tumours. In some clinical studies, an elevated level of IL-1β was found to be associated with low efficacy of anti-cancer therapy and a poor prognosis. In most experimental and clinical studies, the use of IL-1β inhibitors contributed to a decrease in tumour mass and an increase in the response to anti-tumour drugs.     

Endometrial carcinoma stage I

Standard staging and therapeutic approach to endometrial cancer involves lymph node sampling (LNS) at the time of total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO). Lymphadenectomy prolongs time of surgery and increases the risk of morbidity; where other predictors are available, it may not contribute important supplementary information. 185/247 women with stage I endometrial carcinoma underwent the standard surgery while 62 underwent TAH+BSO. Recurrence and survival were monitored for a mean of 6.5 years and retrospectively reviewed: the rates for groups with and without known lymph node status were alike [13.5% (25/185) recurrence for the former and 12.9% (8/62) for the latter, and 5-year survival rates of 75.7% (140/185) for the former and 74.2 (46/62) for the latter]. Myometrial invasion and histological grade appeared to have been highly accurate predictors without lymph node information. Because information on histological grade is available early and is highly predictive, its use could be incorporated into a revised management algorithm for stage I endometrial cancer which would depend upon ensuring lymphadenectomy for women with low grade histopathology and omitting it for those with high grades on the grounds that no further information is necessary to act appropriately.     

Injection of irradiated b16 melanoma genetically-modified to secrete IFN-alpha causes regression of an established tumor

Highly aggressive murine B16 melanoma was engineered to secrete IFN-alpha constitutively. Cells expressing IFN-alpha were injected into syngeneic C57BL/6 mice and the mice were monitored for tumor development. Secretion of IFN-alpha by B16 melanoma cells completely abrogated their tumorigenicity in syngeneic mice. LFN-alpha-secreting cells also abrogated the tumorigenicity of IFN-gamma-secreting and TNF-alpha-secreting cells when injected in combination whereas cells secreting either IFN-gamma or TNF-alpha grow progressively in mice when injected alone. Moreover, protected animals developed significant immunity against subsequent challenge with parental cells. Injection of parental cells and IFN-alpha-secreting cells together in a mixed tumor transplantation assay resulted in a significant reduction of tumorigenicity of the parental cells. Histopathological studies of the tissues from the injection site of the mice inoculated with a combination of parental and B16.IFN-alpha cells revealed the existence of a massive cellular infiltrate composed of lymphocytes and granulocytes at an early stage (7-11 days). In the later stages (22 days), no recognizable tumor tissue was detected. Injection of irradiated IFN-alpha-secreting cells in the mice carrying an established tumor completely prevented tumor development in 80% of the treated mice when injection was performed on the same side as the tumors. Injection of irradiated IFN-alpha-secreting cells in the contralateral site showed much less effect on the established tumor. Systemic antitumor effects on the established tumor can be enhanced by using a combination of irradiated IFN-alpha and IFN-gamma secreting cells as a vaccinating inoculum.     

NGOs in community health insurance schemes: examples from Guatemala and the Philippines

In poor rural communities, access to basic health care is often severely limited by inadequate supply as well as financial barriers to seeking care. National policies may introduce social health insurance, but these are likely to begin with the salaried public and private sector workers while the informal sector population may be the last to be covered. Community initiatives to generate health care financing require a complex development process. This paper covers attempts to develop such schemes in rural populations in Guatemala and the Philippines through non-government organizations and notes the major factors which have contributed to unequal progress in the two schemes. The scheme of the Association por Salud de Barillas (ASSABA) in Guatemala was not sufficiently established as an administrative body at the conceptual stage and there was no clear national policy on health care financing. By the time the necessary action was taken, local conflicts hindered progress. In the Philippines, the ORT Health Plus Scheme (OHPS) was implemented during the period of legislation of a national health insurance act. The appraisal after three years of operation shows that OPHS has made health care affordable and accessible to the target population, composed mainly of low and often unstable income families in rural areas. The major success factors are probably the administrative structure provided by a cooperative and controls in the delivery system and in expenditures, through the salaried primary health care team, referral process and the capitation agreement for hospital-based services. The proliferation of such schemes could benefit from national guidelines, a formal accreditation process and an umbrella organization to provide assistance in design, training and information services, involving government, non-government and academic institutions as an integral part of the development process.     

Suprathreshold Auditory Cortex Activation Visualized by Intrinsic Signal Optical Imaging

The suprathreshold tonotopic organization of rat and guineapig auditory cortex was investigated using intrinsic signaloptical imaging through a thinned skull. Optical imaging revealedthat suprathreshold pure sine wave tone stimulation (25–40dB) evoked activity over large cortical areas that were tonotopicallyorganized. Three-dimensional surface plots of the activatedareas revealed "patchy" auditory-evoked activity consistingof numerous local peaks and valleys building to a maximum. Subsequentdetailed electrophysiological mapping in the same subjects confirmedthe localization of auditory-evoked activity based on opticalimaging, including responses to a test frequency at corticalloci more than 2 octaves away from the threshold-defined isofrequencycontour. The success of this technique in visualizing auditorycortex functional organization at suprathreshold stimulus levelswill allow for future investigations of auditory cortex frequencyrepresentation. including representational plasticity inducedby a variety of experimental manipulations.     

Development of fluridil,a topical suppressor of the androgen receptor in androgenetic alopecia

Nonsteroidal antiandrogens (AA) cannot be topically used for androgenetic alopecia (AGA) because of systemic resorption. A new class of androgen receptor (AR) suppressors designed for safe topical treatment of AGA was synthesized from (3‐amino‐2‐hydroxy‐2‐methyl‐N‐(4‐nitro‐3‐trifluoromethyl)phenyl) propanamide (BP‐34), to contain perfluoroalkyl moieties. The trifluoromethyl derivative (fluridil) at 10 μM decreased expression of the AR in LNCaP human cells by 95%, its serum half‐life was 6 h; it decomposes hydrolytically to BP‐34 and trifluoroacetic acid. Acute intraperitoneal maximum tolerated dose (MTD) of fluridil in mice is 270–300 mg/kg/d and the subacute MTD is 450 mg/kg/d. The oral LD₅₀ in mice was 2,872 mg/kg in males, 2,232 mg/kg in females, and >2,500 mg/kg in rats. Fluridil solution in isopropanol was not cutaneously absorbed in rabbits, did not sensitize or show any phototoxic or photoallergic effects on guinea pig skin, and demonstrated no skin irritation potential in rabbits and humans. Fluridil solid induced only slight and reversible eye irritancy in rabbits and displayed no cytotoxicity to rabbit corneal fibroblasts in vitro. Fluridil demonstrated no significant mutagenicity potential by Ames method. In a double‐blind study, 43 males with AGA, Norwood grade II to Va, used topical 2% fluridil in isopropanol or the vehicle daily for 12 months. Anagens (growing hairs) increased in the fluridil group from 76% to 89%. All hematological and biochemistry values remained within normal range, including testosterone, which varied but seasonally. No fluridil or its decomposition product (BP‐34) was detected in serum. No adverse side effects were reported. Drug Dev. Res. 59:292–306, 2003. © 2003 Wiley‐Liss, Inc.     

Assault,PTSD, Family Substance Use,and Depression as Risk Factors for Cigarette Use in Youth: Findings from the National Survey of Adolescents

A national household probability sample of 4,023 adolescents aged 12 to 17 years was surveyed by telephone via structured clinical interview to determine the impact of familial substance use, sexual and physical assault, witnessed violence, depression and posttraumatic stress disorder (PTSD) on risk of smoking. Results indicated that familial substance use increased risk of smoking only for boys and sexual assault or depression increased risk of smoking only for girls. Age, Caucasian ethnicity, and experiencing physical assault or witnessing violence elevated risk of current cigarette use for both genders. By contrast, PTSD per se was not associated with increased risk of smoking, after the effects of other variables were controlled.     

Cancer Patterns in the Middle East Special Report from the Middle East Cancer Society

To update its cancer statistics, the newly established Middle East Cancer Society examined the cancer frequency patterns in Egypt and the Gaza Strip. The results revealed differing overall patterns. For men the highest frequencies were found for lymphoma, bladder cancer and cancers of the oral cavity and pharynx in Egypt, and for lung cancer, leukaemia and lymphoma in Gaza. For women, breast cancer had the highest frequency in both areas, followed by cancers of the oral cavity and pharynx in Egypt, and leukaemia and lymphoma in Gaza. The distribution of cancer occurrence by organ system also varied. In the light of the different ethnicities, lifestyles, socioeconomic levels and carcinogenic exposure among the countries of the Middle East, this kind of comparison can provide the background for more sophisticated approaches for discerning risk factors in cancer. We believe that further cooperation among participating countries will overcome the present limitations in data collection, registration and access.