Characteristics Of Carcinogenesis Research Articles

Coexistence of Hashimoto’s thyroiditis and papillary thyroid carcinoma

The coexistence of Hashimoto’s thyroiditis (HT) and papillary thyroid carcinoma (PTC) has been a widely debated issue. In view of the current controversy, as well as the high prevalence of both diseases, the objective of the present paper is to evaluate the association between them and to propose the proper therapeutic management. We herein review previous pertinent literature on the subject of concomitant HT and PTC, with respect to epidemiology, clinical presentation, carcinogenesis, and appropriate treatment. Studies to date establish 6.5-43.8% of patients with PTC and coexisting HT, while 11-58.3% of all HT patients will develop PTC. Coexistence of the diseases is significantly related to younger women. Malignant lesions tend to be microcarcinomas, at times multifocal (13.5-44%) and occasionally metastasising to the central cervical compartment (10.8-49%). Mostly, patients have a good prognosis with total thyroidectomy, accompanied by central compartment node dissection in cases with nodal involvement. Many issues, including molecular biological characteristics of carcinogenesis in Hashimoto’s thyroiditis, remain to be clarified and further studies need to be undertaken. The close relationship between HT and PTC lends credence to the hypothesis that autoimmune thyroiditis is a predisposing factor to the development of thyroid carcinoma but patients tend to have favorable clinicopathological characteristics and long recurrence-free survival. A careful surveillance of these patients is required for an early detection of malignant lesions, which should constitute indication for radical surgical treatment.

Breast cancer as heterogeneous disease: contributing factors and carcinogenesis mechanisms

The observed bimodal patterns of breast cancer incidence in the U.S. suggested that breast cancer may be viewed as more than one biological entity. We studied the factors potentially contributing to this phenomenon, specifically focusing on how disease heterogeneity could be linked to breast carcinogenesis mechanisms. Using empirical analyses and population-based biologically motivated modeling, age-specific patterns of incidence of ductal and lobular breast carcinomas from the SEER registry (1990-2003) were analyzed for heterogeneity and characteristics of carcinogenesis, stratified by race, stage, grade, and estrogen (ER)/progesterone (PR) receptor status. The heterogeneity of breast carcinoma age patterns decreased after stratification by grade, especially for grade I and III tumors. Stratification by ER/PR status further reduced the heterogeneity, especially for ER(+)/PR(-) and ER(-)/(-) tumors; however, the residual heterogeneity was still observed. The number of rate-limiting events of carcinogenesis and the latency of ductal and lobular carcinomas differed, decreasing from grade I to III, with poorly differentiated tumors associated with the least number of carcinogenesis stages and the shortest latency. Tumor grades play important role in bimodal incidence of breast carcinoma and have distinct mechanisms of carcinogenesis. Race and cancer subtype could play modifying role. ER/PR status contributes to the observed heterogeneity, but is subdominant to tumor grade. Further studies on sources of "remaining" heterogeneity of population with breast cancer (such as genetic/epigenetic characteristics) are necessary. The results of this study could suggest stratification rather than unification of breast cancer prevention strategies, risk assessment, and treatment.

The tumor promoting effect of lime-piper betel quid in JB6 cells

Betel quid chewing is a general behavior in Taiwan, India, southeastern Asian and South Africa. In this study, microculture tetrazolium test (MTT) showed that the extract of lime-piper betel quid (LPB) (1.0–20 mg/ml) was toxic to JB6 cells. Cells exposed of LPB (0.1, 0.5, 1.0 mg/ml) for 7 days resulted in changes in cytomorphology with characteristics of carcinogenesis. With a long-term treatment (∼30 days) of low doses of LPB (1, 5, 10 μg/ml), the production of H 2O 2 and the activity of myeloperoxidase (MPO) and ornithine decarboxylase (ODC) were increased in JB6 cells. Cell cycle analysis showed a decrease in the G1 phase and an accumulation in the S phase 48 h after LPB treatment. When treating with 0.5 mg/ml LPB for 15 days as a promoter, type III foci were formed in the JB6 culture. These results demonstrated the tumor promotional effect of LPB in JB6 cells.

核内受容体PPARが関与する脂質代謝制御機構と発癌の特性

ペルオキシソーム増殖薬活性化受容体, peroxisome prohferator-acdvated receptor (PPAR) は脂質代謝を含むエネルギーホメオスタシスに関わる核内ホルモン受容体スーパーファミリーのひとつである。リガンドの結合により活性化されると, このリガンドー受容体複合体は転写因子として標的遺伝子のプロモーターに結合し遺伝子発現を誘導する。PPARには構造的・機能的に異なるドメインがあり, それぞれ1) リガンドとの結合, 2) リン酸化, 3) コファクターとの相互作用という独自の機能を果たす。また3種類のアイソフォーム, α, β (δ), γが知られており, それぞれリガンド特異性, 組織分布が異なっている。PPARを活性化させるリガンドには脂肪酸, エイコサノイド, 脂質低下薬, チアゾリジンジオン類など構造的に極めて多岐にわたる化合物が含まれる。したがってPPARは脂質代謝の制御因子の一つとして細胞のエネルギーホメオスタシスに関わると考えられている。一方, PPARの名称の由来となったペルオキシソーム増殖薬とは非遺伝子毒性 (非変異原性) 発癌物質のなかで最大多数を占める一群の化学物質である。これらは細胞内穎粒ペルオキシソームを増殖させる作用があることからこのように呼ばれる。ペルオキシソーム増殖薬による発癌の機構として酸化的ストレスや細胞増殖/分化制御の破綻が重要視されてきたが, この発癌過程にPPARが必須の役割を果たすことが, ノックアウトマウスを用いた研究から明らかになっている。

The effect of high and low salt intake on 7,12-dimethylbenz(a)anthracene-induced hypertension in rats.

Carcinogenesis in female rats, induced by 7,12-Dimethylbenz(α)anthracene (DMBA), is associated with systemic hypertension in over 40% of the treated animals. This hypertension was found to be positively correlated to adrenal hyperplasia. Rats maintained on a sodium-deficient diet rarely tend to develop hypertension and show a lower increment in adrenal weights. The mortality in this group was almost 50%. Rats fed an elevated salt diet disclosed the highest mean blood pressures with rapid onset and the largest increment in adrenal weights, as compared to the animals injected with DMBA alone. Life expectancy is identical, as well as tumour incidence and other characteristics of Carcinogenesis. Changes of the sodium content in the diet influence the adrenal glands, as demonstrated by the data on hypertension and adrenal weights presented; the independence of the adrenolytic action of DMBA on its carcinogenic mechanism was confirmed.

Characteristics of carcinogenesis in muscles with varying metabolism

Two groups of cocks received the same dose of carcinogen (9,10-dimethyl-1,2-benzanthracene) into the thoracic (white) or femoral (red) muscles. Tumors (mostly rhabdomyosarcomas) occurred only in the thoracic muscles in periods of 2 to 5 months after the start of the experiment. Carbohydrate-phosphorus metabolism of this muscle is characterized by the prevalence of anaerobic glycolysis. The dynamics of morphological changes was studied at the site of carcinogen administration in the indicated two types of muscles during the pretumor period. The muscle tissue reaction and protective-adaptive response to the carcinogen administration were different.