It has been known that $\gamma$-irradiation usually induces cell death in regenerating stem cell in normal tissues like skin, intestine and hematopoietic organ. The experiment were carried out to evaluate the early response of radiation injury in radiosensitive and intermediate radiosensitive tissues in feeding and starving rats with the doses of 3.5 and 7.0 Gy. The results of the study showed that the histological phenomenon was apoptosis in the doses of the radiation as the early response of tissue injury. Apoptosis were showed organ-specific and cellular specific responses suggesting that the selection of apoptosis be exactly focused on highly renewal organs and cells. It was interesting that the rats starved for 72 hours prior to irradiation induced less apoptosis in liver than fed rats. As for cellular responses it appeared that apoptotic cells were mostly distributed in ductal or periportal cells in liver of feeding rats unlikely in liver of Starving rots which showed no difference in zonal distribution. In salivary gland apoptotic cells in fed rats were highly induced in intercalating and ductal cell population than in acinar cell population although unlikely in starved rats. This study showed the value of apoptosis using the detection system of TUNEL for evaluating cellular damage after radiation injury and the diminished effect of starvation on cell damage after ionizing irradiation.
Obstructive sialadenitis of major salivary glands is a common entity that occurs either in sialolithiasis or in foreign-body obstruction of the excretory ducts. This is characterized histologically by the presence of duct-like structural groups in a highly fibrotic stroma. Although the pathologic features are well recognized, the various cell types involved in the atrophy and subsequent regeneration of the obstructed salivary gland have been controversial. For this reason, an animal model of obstructive sialadenitis that induced atrophy in the salivary gland was used. Experimental study was performed to observe changes of submandibular gland in rabbit and apply the results to clinical activity. Forty-five rabbits each weighing about 3Kg were used and divided into control and experimental group. In the experimental group, ducts of submandibular gland was ligated and cutted divided into each twenty rabbits. Rabbits were serially sacrificed on the 3rd, 5th, 14th, 30th day of experiment. The submandibular glands were dissected out at sacrifice and stained with H&E, MT, immunohistochemical stain and the histological examinations were carried out under the light and transmission electron microscope. After examination and comparison of all specimens, the results of this study were as follows: 1. In the features of H&E stain, moderate infiltration of inflammatory cell were present at 3rd day of experiment. The features of ductal metaplasia was observed after 7th day in the ligation group and destructive changes was continued. In the cutting group, atrophic changes were less severe than ligation group but the small ductule were separated from stroma after 7th day. 2. In the feature of MT stain, apposition of connective tissue was increased in all group, more active in ligation group. 3. In the features of immunohistochemical stain, ligation group showed increased PCNA positive response at 7th day and the higher activity of duct cells was observed. Severance group showed more PCNA positive response than ligation group at 30th day. 4. In TEM features, ductal metaplasia was started at 7th day and degenerative change with margination of nucleus had been severe. Although ductal metaplasia was seen in the severance group, more numerous granule in different size was founded than ligation group. From above results, degenerative change was identified with ductal metaplasia, apically apposition of granule, r-ER destruction in ligation group. Severance of duct elicit degenerative change of grandular cells but the change was less severe than ligation group and more PCNA positive cell was founded at acinar cell.
The exocrine part of the pancreas has a duct system called the pancreatic ductal system (PDS). Its mechanism of development is complex, and any reorganization during early embryogenesis can give rise to anatomical variants. The aim of this study is to collect, classify, and analyze published evidence on the importance of anatomical variants of the PDS, addressing gaps in our understanding of such variations. The MEDLINE, Web of Science, Embase, and Google Scholar databases were searched to identify publications relevant to this review. R studio with meta-package was used for data extraction, risk of bias estimation, and statistical analysis. A total of 64 studies out of 1,778 proved suitable for this review and metanalysis. The meta-analysis computed the prevalence of normal variants of the PDS (92% of 10,514 subjects). Type 3 variants and "descending" subtypes of the main pancreatic duct (MPD) predominated in the pooled samples. The mean lengths of the MPD and accessory pancreatic duct (APD) were 16.53 cm and 3.36 cm, respectively. The mean diameters of the MPD at the head and the APD were 3.43 mm and 1.69 mm, respectively. The APD was present in only 41% of samples, and the long type predominated. The pancreatic ductal anatomy is highly variable, and the incorrect identification of variants may be challenging for surgeons during ductal anastomosis with gut, failure to which may often cause ductal obstruction or pseudocysts formation.
The purpose of this study is to evaluate an effect of levamisole on the chemical crcinogenesis in the submandibular salivary gland of rats through histopathologic observation. 60 male Sprague Dawley rats were employed in this study, divided into one control and two experimental groups. An pellet of 5 mg of 9, 10-dimethyl-1,2-benzathracene(DMBA) powder was implanted into submandibular salivary gland of each animal among 20 in control. And each animal among 20 in experimental group 1 received 0.7 mg of levamisole hydrochloride orally every day starting at the beginning of the fifth week after DMBA implantation under the same methods as in control. And each animal among 20 in experimental group 2 received the same treatment as in control at the beginning of the fifth week after oral administration of levamisole hydrochloride under the same method as experimental group 1. Each 5 animals in control at the end of 2nd, 4th, 6th 8th, week after experiments, and each 10 animals in experimental group 1,2 at the end of 6th, 8th week after experiments were sacrificed at random. Also the specimens from experimental sites of submandibular salivary glands were routinely processed for histopathologic observation under Hematoxilin-eosin(H-E) staining. The obtained results were as follows : 1. In control, generally, the glandular ductal cell showed the tendency of dysplasia or malignancy with progression of experiment. 2. In experimental group 1, generally, the dysplasia or malignancy of the glandular ductal cell was less prominent than in control, while the lymphocyte infiltration and fibrosis were prominent. 3. In experimental group 2, generally, the dysplasia of the glandular ductal cell was significantly less prominent than in control, while the fibrosis was prominent. 4. Under above results levamisole was thought to delay or prevent the chemical carcinogenesis in the submandibular salivary gland.
Mammary carcinoma with osteoclast-like giant cells is an unusual neoplasm characterized by giant cells, mononuclear stromal cells, and hemorrhage accompanying a low grade carcinoma. We present the cytological findings in a case of invasive ductal carcinoma with osteoclast-like giant cells that was initially confused with a fibroadenoma, due to its well-demarcated and soft mass and the young age of the patient. A 28-year-old female presented with a 4.5 cm, well demarcated, soft and nontender mass in the right breast. Fine needle aspiration cytology (FNAC) showed a combination of low grade malignant epithelial cell clusters and osteoclast-like giant cells. The atypical epithelial cells were present in cohesive sheets and clusters. Osteoclast-like giant cells and bland-looking mononuclear cells were scattered. An histological examination revealed the presence of an invasive ductal carcinoma with osteoclast-like giant cells. We report here the cytological findings of this rare carcinoma in a very young woman. The minimal atypia of the epithelial cells and its soft consistency may lead to a false negative diagnosis in a young woman. The recognition that osteoclastlike giant cells are rarely present in a low grade carcinoma, but not in benign lesion, can assist the physician in making a correct diagnosis.
Fibroblasts are the most common cells in connective tissue and are responsible for the synthesis of extracellular matrix components. The fibrosis associated with chronic inflammation and injury may contribute to cholangiocarcinoma pathogenesis, particularly through an increase in extracellular matrix components, which participate in the regulation of bile duct differentiation during development. Mitochondria produce ATP through oxidative metabolism to provide energy to the cell under physiological conditions. Also, mitochondrial dysfunction and oxidative stress have been implicated in cellular senescence and aging. Alternations in mitochondrial structure and function are early events of programmed cell death or apoptosis and mitochondria appear to be a central regulator of apoptosis in most somatic cell. Clonorchis sinensis, one of the most important parasite of the human bile duct in East Asia, arouses epithelial hyperplasia and ductal fibrosis. Isolated fibroblast from the bile ducts of rats infected by C. sinensis showed increase of cytoplasmic process. In addition, decrease of cellular proliferation was observed in fibroblasts which was isolated from normal rat bile duct and then cultured in media containing C. sinensis excretory-secretory product. However, the effects of C. sinensis infection on the mitochondrial enzyme distribution is not clearly reported yet. Therefore, we investigated the structural change of C. sinensis infected bile duct and mitochondrial enzyme distribution of the cultured fibroblast isolated from the C. sinensis infected rat bile duct. As a result, C. sinensis infected SD rat bile ducts showed the features of chronic clonorchiasis, such as ductal connective and epithelial tissue dilatation, or ductal fibrosis. In addition, fibroblast in ductal connective tissue was damaged by physical effect of fibrotic tissue and chemical stimulation. Immunohistochemically detected mitochondrial electron transferase (ATPase, COXII, Porin) was decreased in C. sinensis infected rat bile duct and cultured fibroblast from infected rat bile duct. It can be hypothesized that the reason why number of electron transferase decrease in fibroblast isolated from the rat bile duct infected with C. sinensis is because dysfunction of electron transport system is occurred mitochondrial dysfunction, increase of ROS (reactive oxygen species) and apoptosis after chemical damage on the cell caused by C. sinensis infection. Overall, C. sinensis infection induces fibrotic change of ductal connective tissue, mutation of cellular metabolism in fibroblast and mitochondrial dysfunction. Consequently, ductal fibrosis inhibits fibroblast proliferation and decreases mitochondrial electron transferase on fibroblast cytoplasm. It was assumed that the structure of bile duct could not normalized and ductal fibrosis was maintained for a long period of time according to fibroblast metamorphosis and death induced by mitochondrial dysfunction.
One case of an unusual form of carcinoma involving the submucosal gland and duct of tongue was reported and reviewed. According to Gerughty et al(1968) four distinct component parts were classified : ductal carcinoma in situ(involvement of the ductal epithelium by in situ carcinomatous changes), squamous cell carcinoma, and a mixed carcinoma(combination of glandular and squamous characteristics and occasionally consisted of large nests composed of "glassy" cell). This tumor was fond to be extremely aggressive and highly malignant. The histopathologic features and the clinical behavior of this tumor were sufficiently distinctive to warrant the designation adenosquamous carcinoma : exhibit concomitant glandular and squamous neoplasm. The mode of therapy was evaluated and the treatment of choice appears to be radical surgery. So, we has done the radical neck dissection and partial glossectomy. However, the limited number of cases indicated that collection and subsequent analysis of additional cases must be performed before any definitive conclusion can be drawn.
Cathepsin D is a protease which is known to facilitate invasion and metastasis of breast carcinoma. Overexpression of cathepsin D is associated with poor clinical outcome and biologic aggressiveness of the breast cancer. We underwent immunocytochemical assay(ICA) for cathepsin D in fine needle aspiration cytology(FNAC) specimens from the breast carcinoma and benign breast diseases. In FNAC specimens cathepsin D was expressed in 21(42.9%) out of 49 cases of invasive ductal carcinoma, whereas negative result was observed in all 15 cases of benign breast diseases including 7 fibroadenomas, 6 fibrocystic diseases, and 2 benign ductal hyperplasias. Among the 11 FNAC specimens from ductal carcinoma in situ(DCIS), cathepsin D was expressed in 3 cases(27.3%). In FNAC specimens immunocytochemistry for cathepsin D showed positive result in 24 out of 60 carcinomas(sensitivity, 40%) and negative result in 15 out of all 15 benign breast diseases(specificity, 100%). No significant correlation was noted between cathepsin D expression in FNAC specimen and clinicohistological characteristics of the breast carcinoma, such as hormone receptors and cell differentiation. In conclusion, ICA of cathepsin D in FNAC specimens thought to be a good adjunct to differentiate malignancy from benign breast diseases.
Objective: The aim of this study was to investigate the clinical significance of annexin a1 (ANXA1) and provide molecular evidence to support that decreased ANXA1 expression could enhance cancer migration and invasion in pancreatic ductal adenocarcinoma (PDAC). Materials and Methods: Immunohistochemistry of a tissue microarray with 162 surgically resected PDAC specimens was performed to examine the expression of ANXA1. We also investigated the relationship between ANXA1 expression and clinicopathological factors and prognosis of PDAC patients. We further studied the role of ANXA1 in PDAC cell proliferation, migration and invasion by cell proliferation assay, migration assay and matrigel invasion assay with reduced ANXA1 expression by RNAi. Western blotting was used to detect matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinase-1 (TIMP-1) expression. We also detected MMP-9 enzyme activity by gelatin zymography. Results: Decreased expression of ANXA1 was significantly associated with poor differentiation, lymph node metastasis and advanced TNM stage of PDAC patients (p<0.05). Moreover, decreased expression of ANXA1 was correlated with poor survival (p<0.05). Furthermore, we found that ANXA1 knockdown inhibited cell proliferation, induced G1 phase cell cycle arrest, increased PDAC cell migration and invasion capacity compared with controls. In addition, Western blotting showed that ANXA1 knockdown increased the MMP-9 protein level and decreased TIMP-1 expression. Gelatin zymography showed that MMP-9 enzyme activity was also elevated. Conclusions: Negative ANXA1 expression is a most unfavorable prognostic factor for PDAC patients. ANXA1 knockdown inhibits cell proliferation by inducing G1 phase cell cycle arrest and increases migration and invasion of PDAC cells through up-regulating MMP-9 expression and activity, implying that ANXA1 may serve as a promising prognostic biomarker and therapeutic target for PDAC.
Breast cancer accounts for one third of new cancer cases among women. The need for biomarkers for early detection is the stimulus to researchers to evaluate altered expression of genes in tumours. Cancer-testis (CT) genes are a group with limited expression in normal tissues except testis but up-regulation in a wide variety of cancers. We here evaluated expression of two CT genes named FBXO39 and TDRD4 in 32 invasive ductal carcinoma samples, 10 fibroadenomas and 6 normal breast tissue samples, in addition to two breast cancer cell lines, MCF-7 and MDA-MB-231, by the means of quantitative real time RT-PCR. FBXO39 showed significant up-regulation in invasive ductal carcinoma samples in comparison with normal samples. It also was expressed in both cell lines and after RHOXF1 gene knock down it was down-regulated in MCF-7 but up-regulated in the MDA-MB-231 cell line. TDRD4 was not expressed in the MCF-7 cell line and any of the tissue samples except testis. However, it was expressed in MDA-MB-231 and was up-regulated after RHOXF1 gene knock down. Our results show that FBXO39 but not TDRD4 can be used for cancer detection and if proved to be immunogenic, might be a putative candidate for breast cancer immunotherapy.
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