Spontaneous tumors in aged SD-JCL rats (author's transl)

Incidence of spontaneous tumors was examined in 77 male and 73 female SD-JCL rats reared throughout their lifespan of 5 to 36 months. Total tumor incidences were 60% and 95% for males and females, respectively. The sex difference was mostly attributable to a high incidence of mammary tumor in females. The pituitary tumor was found in 30% of males and 66% of females aged 5 to 36 months while islet cell tumor of the pancreas and thyroid tumor occurred later and the incidence of latter was particularly high in rats lived more than 2 years. Myeloid leukemia appeared to occur as early as 5 months of age.     

Background pathology in BDF1 mice allowed to live out their life-span

Fifty male and 50 female BDF1 mice were observed allowing them to live out their life-span. Mortality up to 104 weeks of age was higher in males (42%) than in females (34%), and the 50% survival age was 112 weeks for males and 118 weeks for females. Body weight reached the peak at 82 weeks of age in males and 92 weeks of age in females, showing the mean body weight of 54.3 g for males and 48.0 g for females. The incidence of calculi and proteinaceous casts in the kidneys, that were not associated with exposure to chloroform, cell-alteration in the adrenal cortex, and islet cell hyperplasia in the pancreas was significantly higher in males than in females. On the other hand, hyaline droplet degeneration of the renal tubular epithelium, spindle cell proliferation in the adrenal cortex and milk-retention in the mammary glands occurred at a significantly higher incidence in females than in males. Cerebral mineralization in both sexes, atrophy and calcification of the testes and enlargement of the seminal vesicles of males, as well as cyst-formations in the ovary and endometrium of females developed at a very high incidence. Frequent neoplasms in males were hepatocellular adenomas and carcinomas, blood vessel tumours, pulmonary adenomas and carcinomas, and malignant lymphomas. In females, malignant lymphomas were the most common neoplasm, followed by blood vessel tumours, chromophobe pituitary adenomas and hepatocellular adenomas. Hepatocellular carcinomas developed only in males, whereas the histiocytic and lymphocytic types of malignant lymphomas and chromophobe cell adenomas arose solely or at a significantly higher incidence in females than in males.     

Life span and spontaneous tumors incidence of the Wistar Mishima (WM/MsNrs) rat.

The life spans and spontaneous tumors in a total of 1960 Wistar Mishima (WM/MsNrs) rats, inbred strain, from the 80-130th generations were examined. The average life span (mean +/- SD) was 731 +/- 173 days (n = 1053) in the males and 813 +/- 214 days (n = 907) in the females (p < 0.0001). The average life span of tumor-afflicted females was significantly longer than that of the non-tumor group (p < 0.0001), while no such difference was observed in males. Tumors were observed in 33 males (3.1%) and 246 females (27.1%). In the males, tumors were often observed under the skin (2.2%). Frequencies of tumors in lung and liver, bones and intestine were less than 0.5%. In the females, incidence of mammary tumor was 20.1%, and various organs such as ovaries, uterus, bones, lung, and liver had tumor incidence frequencies of less than 3.5%. It was concluded that WM/MsNrs rats might be suitable for life span and age-related studies because of their characteristics of length of longevity and the low incidence of spontaneous tumors in both sexes.     

Cyclin D2 and p27 are tissue-specific regulators of tumorigenesis in inhibin alpha knockout mice

Inhibins are heterodimeric (alpha:betaA and alpha:betaB) endocrine, paracrine, and autocrine factors of the TGFbeta superfamily that are produced predominantly by ovarian granulosa cells in females and testicular Sertoli cells in males. Control of granulosa and Sertoli cell proliferation is lost in the inhibin alpha (Inhalpha) knockout mouse model, leading to gonadotropin-dependent gonadal tumors of the granulosa/Sertoli cell lineage in both females and males. Castrate Inhalpha knockout mice develop sex steroidogenic tumors of the adrenal cortex. Physiological control of granulosa/Sertoli cell cycle progression depends on p27Kip1 and cyclin D2, which function in the G1-->S phase transition. To study the cell cycle-regulatory factors involved in ovarian, testicular, and adrenal tumor development in vivo, we have bred Inhalpha mutant mice to mice with targeted disruptions of the p27 and cyclin D2 genes. Our previous studies demonstrated that inhibins act cooperatively with p27 to negatively regulate granulosa cell proliferation, as double mutant mice lacking inhibins and p27 develop and succumb to ovarian tumors more rapidly than Inhalpha knockout mice. Here, we report that cyclin D2 antagonizes this inhibition and is key in promoting gonadal growth and tumor development, and tumor development is markedly suppressed in double-mutant mice. We found that double-knockout females lacking cyclin D2 and Inhalpha lived longer than mice lacking inhibins alone; the majority of these double-knockout mice lived longer than 17 wk, as opposed to inhibin alpha single-knockout females with 50% survival at between 12 and 13 wk of age. Moreover, 95% of inhibin alpha knockout males succumb to testicular tumor development by 12 wk of age, whereas double knockouts were protected from early signs of tumor development and had a 50% survival of 40 wk. Interestingly, the results of these studies reflect tissue-specific consequences of loss of these cell cycle regulators. In castrate mice, loss of p27 has little effect on adrenal cortical tumor progression in the absence of inhibins, whereas loss of cyclin D2 prolongs the lifespan of cyclin D2, Inhalpha double knockouts. After gonadectomy, 50% of cyclin D2, Inhalpha double-knockout males live to more than 46 wk of age, 10 wk longer than 50% of littermates lacking only inhibins. Similarly, 50% of female cyclin D2, inhibin alpha double knockouts live to 47 wk of age before succumbing to adrenal tumor development, in contrast to the 50% survival of Inhalpha single-knockout females at between 27 and 28 wk. Thus, identification of genetic modifiers of the Inhalpha knockout tumor phenotype has led us to a better appreciation of how specific components of the cell cycle machinery contribute to tumorigenesis in the ovary, testis, and adrenal gland.     

Spontaneous neoplastic lesions in aged Sprague-Dawley rats.

Neoplastic lesions were observed in untreated aged Sprague Dawley (SD) rats throughout their lifespan starting at 5 weeks. Their mean survival times were 89 to 105 weeks of age. The total tumor incidences were 70 to 76.7% and 87 to 95.8% in males and females, respectively. The common neoplasmas were pituitary adenoma and adrenal pheochromocytoma in both sexes, testicular Leydig cell tumor in males and mammary gland tumors, thyroidal C-cell adenoma and uterine stromal polyp in females.     

Estrogen Inhibits Renal Cell Carcinoma Cell Progression through Estrogen Receptor-β Activation

Renal cell carcinoma (RCC) originates in the lining of the proximal convoluted tubule and accounts for approximately 3% of adult malignancies. The RCC incidence rate increases annually and is twofold higher in males than in females. Female hormones such as estrogen may play important roles during RCC carcinogenesis and result in significantly different incidence rates between males and females. In this study, we found that estrogen receptor β (ERβ) was more highly expressed in RCC cell lines (A498, RCC-1, 786-O, ACHN, and Caki-1) than in breast cancer cell lines (MCF-7 and HBL-100); however, no androgen receptor (AR) or estrogen receptor α (ERα) could be detected by western blot. In addition, proliferation of RCC cell lines was significantly decreased after estrogen (17-β-estradiol, E2) treatment. Since ERβ had been documented to be a potential tumor suppressor gene, we hypothesized that estrogen activates ERβ tumor suppressive function, which leads to different RCC incidence rates between males and females. We found that estrogen treatment inhibited cell proliferation, migration, invasion, and increased apoptosis of 786-O (high endogenous ERβ), and ERβ siRNA-induced silencing attenuated the estrogen-induced effects. Otherwise, ectopic ERβ expression in A498 (low endogenous ERβ) increased estrogen sensitivity and thus inhibited cell proliferation, migration, invasion, and increased apoptosis. Analysis of the molecular mechanisms revealed that estrogen-activated ERβ not only remarkably reduced growth hormone downstream signaling activation of the AKT, ERK, and JAK signaling pathways but also increased apoptotic cascade activation. In conclusion, this study found that estrogen-activated ERβ acts as a tumor suppressor. It may explain the different RCC incidence rates between males and females. Furthermore, it implies that ERβ may be a useful prognostic marker for RCC progression and a novel developmental direction for RCC treatment improvement.     

23例鼻腔鼻旁窦恶性黑色素瘤临床病理分析

目的研究鼻腔鼻旁窦恶性黑色素瘤的临床及病理特征。方法采用免疫组化SP方法对23例鼻腔鼻旁窦恶性黑色素瘤的临床及病理进行分析。结果23例鼻腔鼻旁窦恶性黑色素瘤中,男性15例（65．2％）,女性8例（34．8％）;最大年龄80岁,最小年龄45岁,平均年龄57岁;位于鼻腔19例（82．6％）,鼻旁窦4例（17．4％）,临床表现全部为鼻肿物;病理组织学类型,小圆细胞型12例（52．2％）,上皮样细胞型8例（34．8％）,梭形细胞型2例（8．7％）,多形性细型胞1例（4．3％）;含有黑色素13例（56．5％）,无黑色素10例（43．5％）;免疫组化染色,Vimentin,23例全部呈阳性反应,阳性率为100％,S—100和HMB45呈阳性反应的部为21例;阳性率都为91．3％,MelanA 19例呈阳性反应,阳性率占82．6％。结论23例鼻腔鼻窦恶性黑色素瘤,临床主要表现为鼻肿物,发病部位大多数在鼻腔,联合应用S-100,HMB45和Melan A弥漫阳性在与其组织学相似的肿瘤鉴别中是诊断鼻腔鼻窦恶性黑色素瘤的重要标准。     

Incidence analyses of bladder cancer in the Nile delta region of Egypt

Bladder cancer is the most common malignancy among Egyptian males and previously has been attributed to Schistosoma infection, a major risk factor for squamous cell carcinoma (SCC). Recently, transitional cell carcinoma (TCC) incidence has been increasing while SCC has declined. To investigate this shift, we analyzed the geographical patterns of all bladder cancers cases recorded in Egypt's Gharbiah Population-Based Cancer Registry from 1999 through 2002. Data on tumor grade, stage, and morphology, as well as smoking, community of residence, age and sex, were collected on 1209 bladder cancer cases. Age-adjusted incidence rates were calculated for males, females, and the total population for the eight administrative Districts and 316 communities in Gharbiah. Incidence Rate Ratios (IRR) and 95% confidence intervals (CI) were computed using Poisson Regression. The male age-adjusted incidence rate (IR) in Gharbiah Province was 13.65/100,000 person years (PY). The District of Kotour had the highest age-adjusted IR 28.96/100,000 among males. The District of Kotour also had the highest IRR among all Districts, IRR = 2.15 95% CI (1.72, 2.70). Kotour's capital city had the highest bladder cancer incidence among the 316 communities (IR = 73.11/100,000 PY). Future studies on sources and types of environmental pollution and exposures in relation to the spatial patterns of bladder cancer, particularly in Kotour District, may improve our understating of risk factors for bladder cancer in the region.     

Epidemiology of Malignant Melanoma in Central Europe: Risk Factors and Prognostic Predictors. Results of the Central Malignant Melanoma Registry of the German Dermatological Society

The Central Malignant Melanoma Registry (CMMR) of the German Dermatological Society was established in 1983, and 7789 cutaneous malignant melanomas (CMM) were registered by 35 dermatological departments in Germany, Austria and Switzerland until the end of 1989. Population-based incidence rates, risk factors for developing CMM and prognostic parameters for predicting the final outcome were investigated in separate multicenter studies performed by the CMMR. Among the 7789 CMM registered, there was a preponderance of females (57.7%) versus males (42.3%). The age distribution peaked in the 5th and 6th decade of life for both sexes with a mean age of 52 years. The mean detection age was 50 years for superficial spreading melanoma, 53 for nodular melanoma, and 65 for lentigo maligna melanoma. Mean tumor thickness decreased from 2 mm in 1983 to 1.5 mm in 1989, indicating better CMM-awareness of the population and the medical community in this area. 90% of the patients presented with clinical stage I CMM without detectable metastases at first diagnosis. The incidence of CMM in Berlin (West) was assessed based on 960 cases diagnosed between 1980 and 1986. The incidence increased by 49% between 1980-81 and 1985-86, and the age standardized-incidence rate (European standard population) was 9.8 for males and 7.8 for females per 100,000 inhabitants and year in 1985-86. Mortality rates decreased in this period from 3.5 to 2.6 for males and slightly increased for females from 1.2 to 1.6 per 100,000 inhabitants and year. A case control study on the relative risk (RR) for developing CMM revealed the total number of melanocytic nevi (MCN) to be the strongest risk predictor (15x - 50x increased RR), followed by the presence of dysplastic MCN (7x increased RR) and the skin type I (2x increased RR). Interestingly, no differences between CMM-cases and controls were found with respect to the history of sunburns or other parameters of sun exposure in this study. Multivariate analysis of 5093 stage I CMM-patients from four departments with long-term follow-up revealed that tumor thickness is the strongest predictor of survival with an almost linear correlation to the risk of death for tumor thickness up to 6 mm with no further increase in mortality for higher tumor thickness. The best classification of tumor thickness for survival prediction was 1 mm, 1.01 ?2 mm, 2.01 ?4 mm and > 4 mm in our data set on 5093 patients. Sex was found to be the second most important prognostic factor showing a significant advantage for females. Furthermore, a high risk was identified for tumors localized on the upper trunk, upper arm, neck and scalp on the upper trunk, upper arm, neck and scalp (=TANS); the anatomical site, therefore, should be taken into account for a prognostic classification of primary CMM.     

G6PD deficiency in senile cataracts

Summary The incidence of G6PD deficiency among 338 Thai males with senile cataracts was 5.92% while 446 control Thai males gave an incidence of 6.95%. The figures in females were 16.29% and 14% among 201 senile cataracts females and 200 control females respectively. The age of onset of senile cataracts was not different between the G6PD deficient and G6PD normal groups. The findings indicate that, at least in Thailand, G6PD deficiency in general is not a factor in cataractogenesis.     

Effect of testosterone propionate on the induction by 1,2-dimethylhydrazine of angiosarcomas of the renal capsule in castrated mice

Administration of 1,2-dimethylhydrazine (DMH) produced 83% (15/18) of renal capsule angiosarcomas in CBA mice. Castration that preceded the DMH-treatment reduced tumor incidence to 7% (2/29). Simultaneous administration of DMH and testosterone propionate (TP) to castrated males restored the tumor frequency (100%, 24/24). Castrated males that received TP after the cessation of the DMH treatment developed tumors in 10% (3/31). Combined treatment of castrated females with DMH and TP resulted in the development of angiosarcomas in 92% animals (22/24). It is concluded that TP enhances the stage of sarcomogenesis initiation induced by DMH.     

The tumor spectrum of Him:OFA rats]

The longevity and incidence of spontaneous tumors was investigated in 92 male and 182 female rats of the Sprague-Dawley (SD) derived stock Him: OFA. The overall tumour incidence was 85.9% in males and 97.8% in females with 32 different types of tumors in males and 30 in females. The most frequent neoplasms were mammary tumours in females with 84.6% incidence, followed in this sex by adrenal (36.8%), pituitary (32.9%) and thyroid neoplasms (10.9%). The incidence of all neoplasms in female genital tract was 12.6%. In male rats tumours of the adrenals have the highest incidence (53.2%, most of them cortical) followed by pituitary tumours (31.5%) and neoplasm of the mesenteric lymph nodes (14.1%, which is uncommonly high compared with other Sprague-Dawley stocks). All other tumours are below 10% incidence. The mean lifespan of females is with 719 +/- 142 d shorter than that of males with 752 +/- 108 d because of the high incidence of mammary tumours between 16 to 18 months of age.     

Comparison of oropharyngeal and oral cavity squamous cell cancer incidence and trends in New Zealand and Queensland,Australia

BackgroundIncreases in the incidence of squamous cell oropharyngeal cancer (OPC) have been reported from some countries, but have not been assessed in Australia or New Zealand. This study examines trends for squamous cell OPC and squamous cell oral cavity cancer (OCC) in two similarly sized populations, New Zealand and Queensland, Australia.MethodsIncidence data for 1982–2010 were obtained from the respective population-based cancer registries for squamous cell OPC and OCC, by subsite, sex, and age. Time trends and annual percentage changes (APCs) were assessed by joinpoint regression.ResultsThe incidence rates of squamous cell OPC in males in New Zealand since 2005 and Queensland since 2006 have increased rapidly, with APCs of 11.9% and 10.6% respectively. The trends were greatest at ages 50–69 and followed more gradual increases previously. In females, rates increased by 2.1% per year in New Zealand from 1982, but by only 0.9% (not significant) in Queensland. In contrast, incidence rates for OCC decreased by 1.2% per year in males in Queensland since 1982, but remained stable for females in Queensland and for both sexes in New Zealand. Overall, incidence rates for both OCC and OPC were substantially higher in Queensland than in New Zealand. In males in both areas, OPC incidence is now higher than that of OCC.ConclusionsIncidence rates of squamous cell OPC have increased rapidly in men, while rates of OCC have been stable or reducing, showing distinct etiologies. This has both clinical and public health importance, including implications for the extension of human papilloma virus (HPV) vaccination to males.     

Age-related changes in muscle fiber type frequencies and cross-sectional areas in straightbred and crossbred rabbits

This study was designed to investigate the effects of the interaction among genetic group, sex and age on the frequencies and cross-sectional areas of myofiber types in rabbits. A total of 48 straightbred and crossbred Botucatu rabbits, males and females, were involved in a split plot design with a 2 × 2 (genetic groups × genders) factorial arrangement. Young rabbits were weaned at 35 days of age and sequentially slaughtered, four per genetic group × sex combination, at 42, 63 and 84 days of age. The flexor carpi radialis muscle was dissected, histological sections (10 μm) were obtained and the frequencies and cross-sectional areas of myofiber types: I, IIA and IIB/X were determined. An effect of the genetic group × sex × slaughter age interaction was found on the frequency distribution of myofiber types. A transition from type IIA to type IIB/X fibers was observed (P < 0.01) with advancing age, except in crossbred females, but the frequency of IIA fibers was already lower (57.3%) and of IIB/X fibers numerically higher (33.7%) in this group at 42 days. The proportions of IIA fibers in straightbred males, crossbred males and straightbred females decreased from 80.1%, 89.4% and 68.8% at 42 days to 43.9%, 52.3% and 40.1% at 63 days, respectively, whereas the proportions of type IIB/X fibers, in the same groups, increased from 10.3%, 1.6% and 22.3% at 42 days to 42.2%, 37.0% and 49.8% at 63 days, respectively. In all three age points, type IIA fibers showed the largest cross-sectional areas, followed by type I and IIB/X fibers. The cross-sectional areas of IIB/X fibers were larger in crossbreds, but no differences were found between genetic groups concerning fiber types IIA and I. All three types of fibers showed positive linear association with age, but relative to the initial area type IIB/X fibers presented a higher degree of hypertrophy (144% up to 84 days) than type IIA and I fibers (86% and 85%, respectively). The flexor carpi radialis muscle was, on average, heavier in crossbred than in straightbred females, but no difference was observed between crossbred and straightbred males. Differences in the weight of flexor carpi radialis muscle were attributed to the hypertrophy of type IIB/X fibers in the crossbreds.     

A histochemical study on postnatal growth of the soleus muscles of male and female mice

Postnatal changes in histochemical properties of the soleus muscles were examined in male and female mice aged 5 to 40 weeks. The fiber type composition did not significantly differ between sexes 5 weeks after birth. In males the percentage of type I fibers increased from 5 to 22 weeks of age but did not change thereafter. In females the percentage of type I fibers increased from 5 to 40 weeks of age. As a result, females had significantly higher percentage of type I fibers than males 30 and 40 weeks after birth. The smaller increase in the percentage of type I fibers during postnatal growth in males is suggested to be attributable to the higher testosterone level. In males the cross-sectional area of both type I and type II fibers increased with age. In females, however, the cross-sectional area of type II fibers increased with age whereas that of type I fibers increased from 5 to 10 weeks of age but thereafter decreased gradually. The ratio of mean fiber cross-sectional area of type I fibers to that of type II fibers decreased slightly from 5 to 10 weeks of age but did not change thereafter in males. In females the ratio increased from 5 to 10 weeks but thereafter decreased gradually. The ratio was significantly higher in females than in males in all age groups. The percentage area occupied by type I fibers increased with age in both sexes. The increase was greater in females than in males, however. Furthermore, females had significantly higher value than males in all age groups. No significant age difference and sex difference were observed in the total number of muscle fibers.     

Profile of cancer in the Eastern Mediterranean region: The need for action

BackgroundMany countries in the Eastern Mediterranean region (EMR) are undergoing marked demographic and socioeconomic transitions that are increasing the cancer burden in region. We sought to examine the national cancer incidence and mortality profiles as a support to regional cancer control planning in the EMR.MethodsGLOBOCAN 2012 data were used to estimate cancer incidence and mortality by country, cancer type, sex and age in 22 EMR countries. We calculated age-standardized incidence and mortality rates (per 100,000) using direct method of standardization.ResultsThe cancer incidence and mortality rates vary considerably between countries in the EMR. Incidence rates were highest in Lebanon (204 and 193 per 100,000 in males and females, respectively). Mortality rates were highest in Lebanon (119) and Egypt (121) among males and in Somalia (117) among females. The profile of common cancers differs substantially by sex. For females, breast cancer is the most common cancer in all 22 countries, followed by cervical cancer, which ranks high only in the lower-income countries in the region. For males, lung, prostate, and colorectal cancer in combination represent almost 30% of the cancer burden in countries that have attained very high levels of human development.ConclusionsThe most common cancers are largely amenable to preventive strategies by primary and/or secondary prevention, hence a need for effective interventions tackling lifestyle risk factors and infections. The high mortality observed from breast and cervical cancer highlights the need to break the stigmas and improve awareness surrounding these cancers.     

Physical fitness of the Czechoslovak population between the ages of 12 and 55 years. Pulmonary ventilation.

Examination of ventilation function in an average population showed that maximum minute ventilation in adults fell with advancing age. Males had higher values than females, the highest values being attained, in both sexes, at 18 (117 and 83 1/min respectively). Tidal volume during loading, expressed as a percentage of vital capacity, rose with advancing age in all groups of males and females (from 53% at 18 to 64% at 55 in males and from 51% to 59% in females). The ventilation equivalents for O2 and CO2 attained optimum values at a load of 100 W in males and at 50 W in females. On increasing the load they rose in both sexes--in females more than in males. Percentual utilization of O2 from the inspired air was greatest in males at a load of about 100 W (4.8--5%) and in females at about 50 W (4.3--4.8%). At higher loads it fell faster in females than in males. In males, the respiratory quocient attained the value 1 at a load of about 2 W/kg body weight and in females at 1.5 W/kg. At maximum loading it was over 1 in all the age categories. No differences between males and females were observed, but males, in maximum loading, gave the greatest absolute and the greatest relative performance.     

WKY/Ztm-ter: a new rat inbred strain on the WKY/Ztm genetic background with congenital teratomas

We describe a new rat model for teratomas (WKY/Ztm-ter) which arose through a spontaneous mutation in the inbred WKY/Ztm rat strain. When the tumours of the gonads became clinically apparent, affected males were 14 to 224 days of age, whereas the females only developed tumours between days 21 and 63. Tumour incidence is not gender-dependent. However, almost all females develop bilateral tumours, while 50% of the males show unilateral tumours. Histologically, all examined tumours (n = 65) represent partially undifferentiated teratocarcinomas.