Mechanisms of angiogenesis in gliomas

Gliomas are the most frequent primary tumors of the central nervous system in adults. Glioblastoma muhiforme, the most aggressive form of astrocytic tumors, displays a rapid progression that is accompanied by particular poor prognosis of patients. Intense angiogenesis is a distinguishing pathologic characteristic of these tumors and in fact, glioblastomas are of the most highly vascularized malignant tumors. For this reason, research and therapy strategies have focused on derstanding the mechanisms leading to the origin of tumor angiogenic blood vessels in order to develop new approaches that effectively block angiogenesis and cause tumor regression.     

The Pathological Features of Dissemination of Lymphoma in the Heart in 42 Autopsy Cases

OBJECTIVE To study the pathological features of dissemination of lymphoma in the heart and understand its influence on cardiac function.METHODS Forty-two patients who died of lymphoma were autoposied and the gross and microscopic pathological changes of the heart observed.RESULTS Eight (19.05%) out of 42 cases had heart dissemination in the pericardium and heart wall. The dissemination features noted were of a nodular type, diffuse type and mixed type, leading to neoplastic myocarditis.CONCLUSION The pathological features of dissemination of lymphoma in the heart are varied, and the different types can produce dissimilar influences in heart function.     

Role of HIF-1α in response of tumors to a combination of hyperthermia and radiation in vivo

Purpose: Mild temperature hyperthermia (MTH) increases blood flow and oxygenation in tumours. On the other hand, high-dose-per-fraction irradiation damages blood vessels, decreases blood flow and increases hypoxia in tumours. The radiation-induced hypoxia in tumours activates hypoxia-inducible factor-1α (HIF-1α) and its target genes, such as vascular endothelial growth factor (VEGF), promoting revascularization and recurrence. In the present study, we examined the hypothesis that MTH inhibits radiation-induced upregulation of HIF-1α and its target genes by increasing tumour oxygenation.

Materials and methods: FSaII fibrosarcoma tumours grown subcutaneously in the legs of C3H mice were used. Tumours were irradiated with 15?Gy using a ⁶⁰Co irradiator or heated at 41?°C for 30?min using an Oncothermia heating unit. Blood perfusion and hypoxia in tumours were assessed with Hoechst 33342 and pimonidazole staining, respectively. Expression levels of HIF-1α and VEGF were determined using immunohistochemical techniques. Apoptosis of tumour cells was quantitated via TUNEL staining and the effects of treatments on tumour growth rate were assessed by measuring tumour diameters.

Results: Irradiation of FSaII tumours with a single dose of 15?Gy led to significantly decreased blood perfusion, increased hypoxia and upregulation of HIF-1α and VEGF. On the other hand, MTH at 41?°C for 30?min increased blood perfusion and tumour oxygenation, thereby suppressing radiation-induced HIF-1α and VEGF in tumours, leading to enhanced apoptosis of tumour cells and tumour growth delay.

Conclusion: MTH enhances the anti-tumour effect of high-dose irradiation, at least partly by inhibiting radiation-induced upregulation of HIF-1α.     

Expression of TGFα in Meningiomas

The objective of this study was to examine the expression of transforming growth factor (TGF), a mitogen for many cell types, and its receptor in basic subtypes of meningiomas as well as in meningiomas of varying grade. Formalin-fixed tissues from 26 meningiomas including 15 benign (5 meningothelial, 5 transitional, and 5 fibrous variants), 6 atypical, and 5 malignant examples were immunohistochemically examined for both TGF protein and EGF/TGF receptor protein. In addition, in situ hybridization (ISH) was used to detect TGF mRNA expression. Immunostaining for TGF was strongest in fibrous and atypical meningiomas, followed closely by transitional and malignant tumors. Only weak reactivity was observed in the meningothelial variant. In all but 4 tumors (2 fibrous, 2 atypical), ISH showed TGF mRNA to be present, the signal being stronger in malignant than in conventional or atypical tumors. Lastly, immunostaining for EGF/TGF receptor was positive in all tumors studied. Strong TGF protein expression in meningiomas is commonly associated with fibrous morphology. Although the frequent detection of both TGF protein and its mRNA, as well as of EGF/TGF receptor within tumors of all type and grades, suggests that TGF serves to promote tumor growth, its possible role in tumorigenesis or malignant progression is uncertain.In summary, demonstration of these substances is of no utility in the classification or grading of this common tumor because the differences in their expression among the various meningioma subtypes were not statistically significant.     

Over-expression of EGFR in Breast Cancer

Objective： To explore the relationship of overexpression of epidermal growth factor receptor （EGFR） in occurrence, development and treatment of breast cancer. Methods： Samples of 46 breast adenoma tissues and 86 breast cancer tissues were regularly dehydrate-fixed, embedded in paraffin, sliced in to 5μm thick, stained with SABC immunohistochemistry and coloured with DAB. Results： The positive staining of EGFR was shown as brown- yellow and distributed in cytoplasm. The positive rates in the tissues of breast adenosis and breast cancer were 17.04% （6/46） and 56.98% （49/86） respectively. The positive rates of EGFR in the tissue of invasive ductal carcinoma was 64.49% （41/59）, which was significantly higher than that in in situ carcinoma （P〈0.05）. The positive rate of lymph metastasis group was higher than that in non-lymph metastasis group （P〈0.05）. Conclusion： The overexpression of EGFR was related with occurrence, lymph metastasis and pathologic types of breast cancer. The examination of EGFR in the breast cancer can serve as a guidance for target chemotherapy.     

Health-related quality of life in survivors of tumours of the central nervous system in childhood—a preference-based approach to measurement in a cross-sectional study

There is an evident need to measure the comprehensive burden of morbidity experienced by survivors of brain tumours in childhood. To this end, a questionnaire based on the Health Utilities Index mark 2 (HUI2) and mark 3 (HUI3) systems was completed independently for a cohort of such children by their parents, by a nurse, by physicians and by a selected group of the children themselves. Each of the HUI2 and HUI3 systems consists of a multi-attribute health status classification scheme linked to a preference function which provides utility scores for levels within single attributes (domains of health) and for global health states. All eligible families (n=44) participated. Even cognitively impaired children of at least 9.5 years of age could complete the questionnaire. The greatest burden of morbidity, occurring in two-thirds of children, was in the attribute of cognition. Surprisingly, almost one-third of children experienced pain. Global health status was lowest in children who underwent radiotherapy before the age of 5 years and the corresponding utility scores were related inversely to the volume irradiated. Children with demonstrable disease had lower scores than those in whom disease was not evident. There was a high level of agreement (intraclass correlation coefficients >0.5) on formal assessment of inter-rater reliability for global health-related quality of life utility scores. The usefulness of measures of health status and health-related quality of life, in children surviving brain tumours, has been demonstrated by this study.     

Variation in the prevalence of gastric cancer in Perú

Most cases of gastric cancers occur in non-industrialized countries but there is scarce information about the epidemiology of this illness in these countries. Our study examined whether there was a variation in the prevalence of gastric cancer in Lima, Perú over the last 2 decades. Subjects older than 29 years of age were included. They underwent an esophagogastroduedonoscopy at 3 socioeconomically different health facilities in Lima: a county hospital (7,168 subjects), a Peruvian-Japanese Clinic (14,794 individuals) and a private hospital (4,893 individuals). Birth cohort prevalence of gastric cancer was used. Regression models were calculated to predict the future prevalence of gastric cancer. It was found that the birth cohort prevalence of gastric cancer decreased in Perú from 22.7 to 2% (p < 0.001), from 12 to 0.5% (p < 0.001), and from 6.5 to 0.1% (p < 0.001) in the low, middle and high socioeconomic group, respectively. The prevalence of intestinal metaplasia decreased from 44.3 to 12.5% (p < 0.001), from 28.4 to 5% (p < 0.001), and from 19.4 to 2.2% (p < 0.001) in the low, middle and high socioeconomic status, respectively. These trends will likely persist over the future decades. Nevertheless, the prevalence of gastric cancer remains high in subjects older than 59 years of age in the low socioeconomic status. It is concluded that the prevalence of gastric cancer is decreasing in Perú, similar to the current trend undergoing in industrialized nations. However, there are still specific groups with high prevalence that might benefit from screening for early detection and treatment.     

Are there socio-economic inequalities in age of resection of colorectal cancer in people with HNPCC?

The relationship between socio-economic status and health has been consistently reported and is thought to be causal. Socio-economic inequalities are present in the incidence of and mortality from cancer in general, but not in the incidence of colorectal cancer in particular. However, there are socio-economic gradients in mortality from colorectal cancer. The socio-economic distribution of incidence of and mortality from colorectal cancer in individuals with hereditary non-polyposis colon cancer (Lynch syndrome) is not known. It is possible that increased awareness of and access to screening for colorectal cancer amongst this group of individuals reduces the socio-economic gradients seen in the population as a whole. We investigated the relationship between socio-economic status and age of resection of colorectal cancer in a cohort of individuals with hereditary non-polyposis colon cancer. More affluent individuals tended to undergo surgical resection for colorectal cancers earlier in their lives than less affluent individuals. This relationship was bordering on statistical significance. This trend probably represents socio-economic variations in access to treatment. In addition, age based diagnostic criteria for hereditary non-polyposis colon cancer may, inadvertently, accentuate socio-economic inequalities in outcome.     

Characteristics of in vitro antiproliferation activity of human interferon-β

Summary We compared the in vitro antiproliferative activity of highly purified interferon (IFN)- (>10⁷ U protein/mg in antiviral activity) with that of IFNs- and lymphoblastoid, using human cells of malignant and non-malignant origin. IFN- was the least active of three IFNs in suppressing Daudi cell proliferation. Three hematological cells other than Daudi cells cultivated in suspension were insensitive to each of three IFNs. IFN- was more active than IFNs- and lymphoblastoid in suppressing all eight epithelioid cells tested and, particularly with respect to five epithelioid cells sensitive to IFN, IFN- was seven to 49 times as active as IFN-. These results indicate that suppression of cell proliferation by IFN depends not only on the target cell species but also on the IFN species, and emphasize the need for careful selection of the most appropriate IFN species in therapy.We found that the antiproliferative characteristics of the present IFN- preparation were consistent with those reported previously, supporting the idea that IFN- molecules in the present preparation were responsible for suppressing cell proliferation. The antiproliferation activity of our preparation was species-specific but not selective for cells of malignant origin; it was absorbable by IFN-sensitive but not by IFN-insensitive cells; and it was achieved by a cytostatic effect.     

Nonoperative management of gastrointestinal malignancies in era of neoadjuvant treatment

Cancers derived from the gastrointestinal(GI) tract are often treated with radical surgery to achieve a cure.However, recent advances in the management of GI cancers involve the use of a combination of neoadjuvant radiation and chemotherapy followed by surgical intervention to achieve improved local control and cure.Interestingly, a small proportion of patients with highly sensitive tumors achieved a pathological complete response(pCR)(no residual tumor cells in the resected specimen) to neoadju...     

Time for a re-evaluation of mammography in the young? Results of an audit of mammography in women younger than 40 in a resource restricted environment

Mammography in younger women is considered to be of limited value. In a resource restricted environment without access to magnetic resonance imaging (MRI) and with a high incidence of breast cancer in the young, mammography remains an important diagnostic tool. Recent technical advances and better regulation of mammography make a reassessment of its value in these conditions necessary. Data of all the mammograms performed at a tertiary hospital and private breast clinic between January 2003 and July 2009 in women less than 40 years of age were collected. Indications were the presence of a mass, follow-up after primary cancer therapy, and screening for patients perceived at high risk due to a family history or the presence of atypical hyperplasia. Data acquired were as follows: Demographics, prior breast surgery, indication for mammography, outcome of mammography, diagnostic procedures, and their results. Of 2,167 mammograms, 393 were performed for a palpable mass, diagnostic mammography. In these, the overall cancer detection rate was 40%. If the mammography was reported as breast imaging reporting and data system (BIRADS^®) 5 versus BIRADS^® 3 and 4 versus BIRADS^® 1 and 2, a final diagnosis of malignancy was established in 96, 48, and 5%, respectively. Of 367 mammograms done for the follow-up after primary treatment of breast cancer, seven cancers were diagnosed for a detection rate of 1.9%. Of 1,312 mammograms performed for screening, the recall rate was 4%; the biopsy rate 2%, and the cancer diagnosis rate 3/1,000 examinations. In contrast to past series, this series has shown that recent advances in mammography have made it a useful tool in the management of breast problems in young women, notably in a resource-restricted environment. Women for screening should be selected carefully.     

Analysis of Pathogenic Factors of Helicobacter Pylori in a High Prevalence Area of Gastric Cancer in Xinin,Qinghai Province

OBJECTIVE To analyze positive rates of the specific proteins CagA, VacA, UreA and UreB of Helicobacter pylori (Hp) in people in Xinin city Qinghai Province, a district with a high prevalence of gastric carcinoma, and to examine the relationship among the incidence, gross diagnosis and pathologic diagnosis. METHODS The gastric tissue biopsy specimens taken under endoscopy were examined by CLO,WS and Western Blot to judge the condition of the Hp infection. The positive rates of Hp CagA,VacA,UreA and UreB that had infected patients were evaluated. RESULTS The positive rate of UreA was markedly lower in chronic superficial gastritis (CSG) than in duodenal ulcer (DU) and compound ulcer, and also lower than in chronic atrophic gastritis(CAG), gastric ulcer(GU) and gastric cancinoma. However the positive rate of UreB was notably lower in duodenal ulcer and gastric ulcer than in chronic superficial gastritis and atrophic gastritis. The rates of UreB found in intestinal epithelial metaplasia, atrophic gastritis and gastric carcinoma were notably lower than in other diseases, however, it was markedly increased in chronic superficial gastritis, No differences were found among CagA and VacA of specimens with different endoscopic diagnosis or pathologic diagnosis. CONCLUSIONS The UreA in Hp may be relevant to the pathogenic mechanism of severe gastric diseases. However, UreB may have some protective effect on severe gastric diseases.     

Specific changes in the parameters of blood antioxidant status in patients with cervical carcinoma in the course of cancer therapyĭ

Parameters of the blood and plasma antioxidant systems were investigated at different stages of specific therapy for T3NxM0 cervical tumors in 23 patients to identify mechanisms of "relative" drug resistance. Treatment included preoperative telegammatherapy (10 Gy), aregional and regional lymphinfusion with low and high doses of cytostatics, respectively, complemented with endolymphatic injection of tocopherol acetate 100 ng. As a result, surgery after Wertheim became feasible in 14 out of 23 patients following external exposure to 30-40 Gy. Morphological examination detected metastases into the regional lymph nodes in 3 patients. The advantages offered by the treatment modality include adequate response to therapy as well as access to control of free-radical processes taking place in membranes of immunocompetent cells which in turn assures good clinical results.     

What is new in melanoma research: genetics and epidemiology of melanoma in 2003? Review of a workshop held in Milan in May 2003

The various papers that were presented during this symposium touched on two of the most important aspects concerning melanoma because they dealt with epidemiology and genetics. Secondary prevention represents the most important step to cure melanoma patients once the disease has presented on a patient. It is clear that educational campaigns lead to greater awareness of the public and hence better prevention and earlier diagnosis. A second item is becoming more and more important in the field of prevention and early diagnosis, which is to understand the genetic basis of melanoma etiology and development. Studies concerning the familial clustering, for example, can lead to more careful monitoring of patients for other tumours and also lead to a basis for further research.     

Progress in the Management of Malignant Pleural Mesothelioma in 2017

Malignant pleural mesothelioma (MPM) is an uncommon, almost universally fatal, asbestos-induced malignancy. New and effective strategies for diagnosis, prognostication, and treatment are urgently needed. Herein we review the advances in MPM achieved in 2017. Whereas recent epidemiological data demonstrated that the incidence of MPM-related death continued to increase in United States between 2009 and 2015, new insight into the molecular pathogenesis and the immunological tumor microenvironment of MPM, for example, regarding the role of BRCA1 associated protein 1 and the expression programmed death receptor ligand 1, are highlighting new potential therapeutic strategies. Furthermore, there continues to be an ever-expanding number of clinical studies investigating systemic therapies for MPM. These trials are primarily focused on immunotherapy using immune checkpoint inhibitors alone or in combination with other immunotherapies and nonimmunotherapies. In addition, other promising targeted therapies, including pegylated adenosine deiminase (ADI-PEG20), which focuses on argininosuccinate synthase 1–deficient tumors, and tazemetostat, an enhancer of zeste 2 polycomb repressive complex 2 subunit inhibitor of BRCA1 associated protein 1 gene (BAP1)-deficient tumors, are currently being explored.