Cathepsin D Expression in Colorectal Adenocarcinomas and Adenomas

2002 ◽  
Vol 17 (3) ◽  
pp. 165-168 ◽  
Author(s):  
Y. Kanber ◽  
N.R. Demirbag ◽  
A.D. Sam ◽  
N. Aydin

The aim of this study was to investigate the role of cathepsin D in colorectal cancer. For this purpose cathepsin D expression was evaluated by means of immunohistochemistry in stromal and tumor cells of 31 colorectal carcinomas and 29 adenomas. Cytoplasmic cathepsin D expression of tumor cells was present in 90.3% of the carcinoma cases and various degrees of stromal cell cathepsin D expression were present in all cases. In the adenomas, the epithelial cells and stromal cells expressed cathepsin D in 68.96% and 96.55% of cases, respectively. The staining intensity was always weaker in the adenomas. When the stromal and tumor cell cathepsin D expression in the adenocarcinoma and adenoma cases were compared, a statistically significant difference was observed in the staining of stromal cells. Furthermore, stromal cathepsin D expression in the adenocarcinomas was related to tumor stage when the carcinomas were divided into low and high stage. Cathepsin D expression in stromal cells may be an important indicator of poor prognosis in colorectal adenocarcinomas.

2020 ◽  
Vol 11 (11) ◽  
Author(s):  
Chunliang Shang ◽  
Jie Qiao ◽  
Hongyan Guo

AbstractThe pre-metastatic niche is a favorable microenvironment for the colonization of metastatic tumor cells in specific distant organs. Lipid droplets (LDs, also known as lipid bodies or adiposomes) have increasingly been recognized as lipid-rich, functionally dynamic organelles within tumor cells, immune cells, and other stromal cells that are linked to diverse biological functions and human diseases. Moreover, in recent years, several studies have described the indispensable role of LDs in the development of pre-metastatic niches. This review discusses current evidence related to the biogenesis, composition, and functions of LDs related to the following characteristics of the pre-metastatic niche: immunosuppression, inflammation, angiogenesis/vascular permeability, lymphangiogenesis, organotropism, reprogramming. We also address the function of LDs in mediating pre-metastatic niche formation. The potential of LDs as markers and targets for novel antimetastatic therapies will be discussed.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Satu Salmi ◽  
Anton Lin ◽  
Benjamin Hirschovits-Gerz ◽  
Mari Valkonen ◽  
Niina Aaltonen ◽  
...  

Abstract Background FoxP3+ Regulatory T cells (Tregs) and indoleamine-2,3-dioxygenase (IDO) participate in the formation of an immunosuppressive tumor microenvironment (TME) in malignant cutaneous melanoma (CM). Recent studies have reported that IDO expression correlates with poor prognosis and greater Breslow’s depth, but results concerning the role of FoxP3+ Tregs in CM have been controversial. Furthermore, the correlation between IDO and Tregs has not been substantially studied in CM, although IDO is known to be an important regulator of Tregs activity. Methods We investigated the associations of FoxP3+ Tregs, IDO+ tumor cells and IDO+ stromal immune cells with tumor stage, prognostic factors and survival in CM. FoxP3 and IDO were immunohistochemically stained from 29 benign and 29 dysplastic nevi, 18 in situ -melanomas, 48 superficial and 62 deep melanomas and 67 lymph node metastases (LNMs) of CM. The number of FoxP3+ Tregs and IDO+ stromal immune cells, and the coverage and intensity of IDO+ tumor cells were analysed. Results The number of FoxP3+ Tregs and IDO+ stromal immune cells were significantly higher in malignant melanomas compared with benign lesions. The increased expression of IDO in melanoma cells was associated with poor prognostic factors, such as recurrence, nodular growth pattern and increased mitotic count. Furthermore, the expression of IDO in melanoma cells was associated with reduced recurrence˗free survival. We further showed that there was a positive correlation between IDO+ tumor cells and FoxP3+ Tregs. Conclusions These results indicate that IDO is strongly involved in melanoma progression. FoxP3+ Tregs also seems to contribute to the immunosuppressive TME in CM, but their significance in melanoma progression remains unclear. The positive association of FoxP3+ Tregs with IDO+ melanoma cells, but not with IDO+ stromal immune cells, indicates a complex interaction between IDO and Tregs in CM, which demands further studies.


2003 ◽  
Vol 89 (3) ◽  
pp. 305-310 ◽  
Author(s):  
Volkan Baltaci ◽  
Semra Sardas ◽  
Bulent Aytac ◽  
Sami Cakar ◽  
Ali Esat Karakaya

Aims, Background and Study Design Few studies have investigated the karyotypes of colorectal carcinomas with emphasis on the correlation between cytogenetic findings and clinicopathologic features. The aim of our study involving 20 colorectal adenocarcinomas was to determine their genomic alterations at the chromosomal level by correlating the cytogenetic findings with the extent of DNA damage and clinicopathologic parameters and to compare the results with those of healthy controls. Results Cytogenetic evaluation of patients and controls revealed 10 abnormal karyotypes in patients with adenocarcinomas located in the rectum, sigmoid and rectosigmoid regions. Four had numerical and six had structural abnormalities. Conclusions Statistical analysis revealed a significant difference compared with controls (P <0.01). The karyotypes and the extent of DNA damage assessed by the comet assay were also significantly correlated with tumor stage (P <0.01) using the Kruskal-Wallis non-parametric test, while no statistical significance was observed in relation to patient age and smoking.


2020 ◽  
Vol 10 (2) ◽  
pp. 15-25
Author(s):  
Amrallah A. Mohammed ◽  
Hanna M. Ibrahim ◽  
Hanna A. Atwa ◽  
Ayman Elshentenawy ◽  
Amira Elwan

AbstractBackgroundDisturbance in cell cycle regulatory genes is a common finding among many types of cancers. The aim of this study is to evaluate the role of cyclin D1 and DJ-1 in benign prostatic hyperplasia (BPH) and prostate cancer (PC).MethodThe current study enclosed 40 patients diagnosed with PC and 40 cases of BPH. The expression level of cyclin D1 and DJ-1 were evaluated by immunohistochemistry (IHC). Cyclin D1 scored depending on the percentage of stained nuclear tumor cells. While scoring of DJ-1 was based on intensity. The results were correlated with clinicopathological features and outcome.ResultsIn the PC group, cyclin D1 was detected in 95% and overexpressed in 42.5%, DJ-1 was positively stained in 85% and overexpressed in 47.5%. Meanwhile, in the BPH group, cyclin D1 was not detected and DJ-1 stained in only 2.5%. There was a statistically significant difference in Gleason score (GS), tumor stage, size, and treatment failure (p =< 0.001). In the terms of PC diagnosis prediction, although cyclin D1 was more specific (100%), DJ-1 is more sensitive than cyclin D1 (80%, 70%, respectively) (p = 0.000).ConclusionsCyclin D1 and DJ-1 may emerge as a promising way for diagnosis of PC in certain circumstances, as the presence of insufficient tissue sampling, small foci of carcinoma or benign lesions mimic PC. This is in addition to the known role of cyclin D1 and DJ-1 in PC prognosis.


1991 ◽  
Vol 3 (3) ◽  
pp. 321 ◽  
Author(s):  
RA Cherny ◽  
LA Salamonsen ◽  
JK Findlay

Immunocytochemistry with monoclonal antibodies to the oestrogen receptor (ER) was used to localize ERs in sections of endometrium obtained from cycling and pregnant Corriedale ewes. Representative tissue from Days 4, 10, 14, 15, 16 and 17 of the cycle (Day 0 = onset of oestrus) and Day 15 of pregnancy was used. ER localization was also examined in tissue obtained from ovariectomized (ovex) ewes with and without subcutaneous implants containing oestrogen, progesterone, or oestrogen and progesterone. ER distribution was examined in caruncular endometrium and intercaruncular endometrium. Staining intensity varied according to cell type, stage of the cycle, steroid treatment and pregnancy. No staining was observed in endothelial cells. In all cases, ER was localized within the nuclei of positive cells. Generally, ER levels were high on Day 4 and declined to negligible values by Day 10 (corresponding to peak progesterone values) except in the deep stroma of caruncular endometrium. Positive staining reappeared in stromal cells of caruncles on Day 13 and in the luminal epithelium of intercaruncular tissue on Day 14. Peak intensity was reached on Day 15 for caruncular tissue and Day 16 for intercaruncular tissue. Ovariectomy did not cause an overall reduction in ER levels, whereas treatment with oestrogen and progesterone had variable effects depending on cell type. Progesterone did not suppress overall ER. In Day 15 pregnant tissue, ER was undetectable in all compartments except deep stroma of caruncles, indicating that factors other than progesterone, perhaps embryonic in origin, were responsible. The observation that individual cell types display differential sensitivities to oestrogen and progesterone as regards their expression of ER is consistent with the role of cell-cell interactions as modulators of cellular response to steroids through the oestrous cycle and in pregnancy.


2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 394-394
Author(s):  
Jasreman Dhillon ◽  
Anders E. Berglund ◽  
Julio Pow-Sang ◽  
Philippe E. Spiess ◽  
Anthony M. Magliocco

394 Background: Penile carcinoma accounts for 0.4% to 0.6% of all malignancies in men. Due to its low incidence the prognostic role of clinicopathological characteristics, p16, p53 and HPV infection remains unclear. We report our experience with p16, p53 and HPV ISH (types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 66) in determining the aggressive nature of this carcinoma. Methods: A tissue microarray (TMA) of 57 cases of invasive penile squamous cell carcinomas was immunohistochemically stained with immunohistochemical stains p16 and p53. HPV ISH was performed as well. The TMA slides were scored semi quantitatively by a specialized genitourinary surgical pathologist. The H score was calculated for p53 using a combination of staining intensity and extent according to the following formula: H score = 1 x % of tumor cells with weak staining + 2 x % of tumor cells with moderate staining + 3 x % of tumor cells with strong staining, resulting in a total score of 0 – 300. Calculations for p53 were done considering values above 0 as positive. For p16 and HPV ISH, the results were recorded as negative or positive. The overall survival curves for up to 60 months were estimated by Kaplan-Meier (KM) method. Results: HPV ISH was positive in 23 cases and p16 was positive in 23 cases as well. However, there were 9 discordant cases between the two (p16+/HPV ISH- = 5; p16-/HPV ISH+ = 4). p53 was positive in 39 cases. Tumors positive for HPV ISH had a better survival as compared to HPV ISH negative tumors (p = 0.0040; Hazard ratio 4.991). Whereas p16 (p = 0.206; Hazard ratio 1.838) and p53 (p = 0.1582; Hazard ratio 0.5198) were not significantly associated with survival at 60 months. Conclusions: Overall HPV positive penile carcinomas appear to have a distinct biology with better prognosis. There is no significant difference in survival for tumors with different p16 and p53 expression.


2021 ◽  
Author(s):  
Bhaskar Basu ◽  
Subhajit Karmakar

Extracellular vesicles (EVs) are cell-derived lipid membrane bound vesicles that serve as mediators of intercellular communication. EVs have been found to regulate a wide range of cellular processes through the transference of genetic, protein and lipid messages from the host cell to the recipient cell. Unsurprisingly, this major mode of intracellular communication would be abrogated in cancer. Ever increasing evidence points towards a key role of EVs in promoting tumor development and in contributing to the various stages of metastasis. Tumor released EVs have been shown to facilitate the transference of oncogenic proteins and nucleic acids to other tumor cells and to the surrounding stromal cells, thereby setting up a tumor permissive microenvironment. EVs released from tumor cells have been shown to promote extracellular matrix (ECM) remodeling through the modulation of neighboring tumor cells and stromal cells. EVs released from disseminated tumor cells have been reported to attract circulating tumor cells (CTCs) via chemotaxis and induce the production of specific extracellular matrix components from neighboring stromal cells so as to support the growth of metastatic cells at the secondary tumor site. Circulating levels of tumor derived EVs of patients have been correlated with incidence of metastasis and disease relapse.


2005 ◽  
Vol 8 (1) ◽  
pp. 17
Author(s):  
Baik Hyeon Jo ◽  
Doy Il Kim ◽  
Won Hung Lee ◽  
Tae Jin Lee ◽  
Jae Hyung Yoo ◽  
...  

2020 ◽  
pp. e2020106
Author(s):  
Maryam Aghighi ◽  
Bruce Smoller

Background: Bullous pemphigoid (BP) is a subepidermal blistering disorder caused by autoantibodies directed against hemidesmosomal proteins. Many patients with BP demonstrate circulating IgE autoantibodies. Although the role of IgE in the pathogenesis of BP is unknown, a correlation between IgE antibodies and eosinophilia has been observed. Soluble CD23 and galectin-3 are the main elements of the IgE group. The roles for CD23 in BP as a potential biomarker and IgE production regulator have been characterized, but no studies have evaluated any roles for galectin-3 in this disease. Objectives: In this study, we evaluated galectin-3 expression in BP as a first step in assessing its role in the pathogenesis of this autoimmune blistering process.  Patients and Methods: Sixty specimens diagnosed as BP were stained with antibodies to galectin-3. The percentages of nuclear and cytoplasmic galectin-3 expression and staining intensity were evaluated. Results: There was a significant difference in galectin-3 cytoplasmic and nuclear expression within keratinocytes immediately surrounding and above the blisters: (1) cytoplasmic (mean = 17.2% ± 2.4%) vs adjacent unaffected skin (mean = 66.7% ± 2.0%, P < 0.0001) and (2) nuclear (mean = 1.9% ± 0.4%) vs adjacent unaffected skin (mean = 13.2% ± 1.2%, P < 0.0001). Conclusions: Lower expression of galectin-3 around blisters in BP may suggest a role as an adhesion molecule. Loss of galectin-3 may add to the extension of blister formation by initiating cell-extracellular matrix disassembly and may be involved with the associated dermal inflammation and the eosinophil chemotaxis. Further studies will be necessary to elucidate the result of this observed loss on disease pathogenesis.


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