Pyrazole (1, 2-diazole) induce apoptosis in lymphoma cells by targeting BCL-2 and BCL-XL genes and mitigate murine solid tumour development by regulating cyclin-D1 and Ki-67 expression

2021 ◽  
Vol 418 ◽  
pp. 115491
Author(s):  
Walsan Kalarikkal Vishnu ◽  
Prathapan Abeesh ◽  
Chandrasekharan Guruvayoorappan
Keyword(s):  
Cyclin D1 ◽  
Solid Tumour ◽  
Lymphoma Cells ◽  
Ki 67 ◽  
Tumour Development

Dantrolene Potentiates the Antineoplastic Effect of Sorafenib in Hepatocellular Carcinoma via Targeting Ca+2/PI3K Signaling Pathway

2021 ◽  
Vol 14 ◽  
Author(s):  
Sherin Zakaria ◽  
Abeer Ansary ◽  
Nabil M. Abdel-Hamid ◽  
Mamdouh M. ElShishtawy
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cyclin D1 ◽  
Antineoplastic Agent ◽  
Inhibitory Effect ◽  
Pi3k Pathway ◽  
Ki 67 ◽  
Antineoplastic Effect ◽  
Pi3k Signaling Pathway ◽  
Proliferation And Metastasis

Background: Hepatocellular carcinoma (HCC) is the 6th prevalent cancer and the 4th leading cause of cancer related deaths all over the world. A major challenge for sorafenib, the standard chemotherapeutic agent in HCC treatment, is the chemo-resistance. Objective: This study was conducted to evaluate the role of dantrolene as a possible antineoplastic agent in HCC, and in chemo-sensitization of sorafenib via targeting Ca+2/PI3K pathway. Methods: HCC was induced in rats using a single dose of diethyl nitrosamine (DENA) (200 mg/kg, ip), followed by phenobarbital sodium (0.05%) in drinking water for 18 weeks. At the end of 18th week, rats were allocated into 4 groups (10 rats/each), one group was left without treatment (DENA group) and the other three groups were treated with either sorafenib, dantrolene, or their combination for further 4 weeks. One day after last injection, serum and liver tissues were collected. Liver tissue p53, VEGF, MMP-9, Cyclin D1, PI3K, and, serum AFP were assessed using immunoassay. Hepatic and serum Ca+2 were also computed. Furthermore, Ki67 was assessed immunohistochemically. Results: Dantrolene exhibited synergistic effect when used in combination with sorafenib compared to either drug alone (p <0.05) through decreasing p53, VEGF, MMP-9, Cyclin D1, and Ki-67. In addition, dantrolene was evidenced to have an inhibitory effect on Ca+2/PI3K pathway that mediates its antineoplastic action when used alone or in combination with sorafenib. Conclusion: Dantrolene exerted antineoplastic effect as well as augmented sorafenib antineoplastic activity via intervention of Ca+2/PI3K pathway, manifested by ameliorating angiogenesis, apoptosis, proliferation and metastasis.

Expression of cyclin D1 and Ki-67 in squamous cell carcinoma of the oral cavity: clinicopathological and prognostic significance

Oral Oncology ◽  
2002 ◽  
Vol 38 (3) ◽  
pp. 301-308 ◽  
Author(s):  
Juan Carlos de Vicente ◽  
Agustı́n Herrero-Zapatero ◽  
Manuel Florentino Fresno ◽  
Juan Sebastián López-Arranz
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Cavity ◽  
Cell Carcinoma ◽  
Cyclin D1 ◽  
Squamous Cell ◽  
Prognostic Significance ◽  
Ki 67

scholarly journals IMP3 Protein Overexpression Is Linked to Unfavorable Outcome in Laryngeal Squamous Cell Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4306
Author(s):  
Diana Maržić ◽  
Blažen Marijić ◽  
Tamara Braut ◽  
Stefan Janik ◽  
Manuela Avirović ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Protein Expression ◽  
Cell Carcinoma ◽  
Cyclin D1 ◽  
Squamous Cell ◽  
Expression Patterns ◽  
Low Grade ◽  
Benign Lesions ◽  
Ki 67 ◽  
Neck Node

Background: The aim of this study was to (i) determine IMP3 protein expression in benign and malignant laryngeal lesions, (ii) compare its expression to Ki-67, p53, cyclin D1, and (iii) finally, to examine the prognostic power of IMP3 in squamous cell carcinomas of the larynx (LSSC). Methods: IMP3 protein expression was evaluated in 145 patients, including 62 LSCC, 45 dysplasia (25 with low and 20 with high-grade dysplasia), and 38 benign lesions (vocal cord polyps and nodules). Results: IMP3 was significantly higher expressed in LSCC compared to dysplasia and benign lesions (p < 0.001; p < 0.001, respectively). Similarly, higher expression patterns were observed for Ki-67 and p53, whereas cyclin D1 was equally distributed in all three lesions. IMP3 (p = 0.04) and Ki-67 (p = 0.02) expressions were significantly linked to neck node positivity, and IMP3 overexpression to worse disease-specific survival (p = 0.027). Conclusion: Since IMP3 showed significantly higher expression in laryngeal carcinomas, but not in high- or low-grade dysplasia, it serves as a useful marker to differentiate between invasive and noninvasive lesions. Higher IMP3 expression represented a significantly worse prognosticator for clinical outcomes of patients with squamous cell carcinoma of the larynx.

Differential Expression of Cyclin D1 in Breast Papillary Carcinomas and Benign Papillomas

1999 ◽  
Vol 123 (2) ◽  
pp. 152-156
Author(s):  
M. Saddik ◽  
R. Lai ◽  
L. J. Medeiros ◽  
A. McCourty ◽  
R. K. Brynes
Keyword(s):  
Cyclin D1 ◽  
Papillary Carcinoma ◽  
Regulatory Protein ◽  
Immunohistochemical Method ◽  
Breast Carcinomas ◽  
Ki 67 ◽  
Cell Cycle Regulatory Protein ◽  
The Difference ◽  
Breast Tissues ◽  
Formalin Fixed

Abstract Objectives.—Distinguishing intraductal papilloma from papillary carcinoma of the breast can be difficult using histologic criteria. Since cyclin D1, a G1 cell-cycle regulatory protein, is detectable immunohistochemically in a subset of breast carcinomas but not in benign breast tissues, we hypothesized that cyclin D1 immunoreactivity may be a marker for identifying papillary carcinoma. Methods.—Using an immunohistochemical method, we assessed for cyclin D1 expression in 8 breast papillomas and 6 papillary carcinomas, all of which were formalin fixed, routinely processed, and paraffin embedded. Cyclin D1 positivity also was compared with the overall proliferation rate, which was assessed by using the proliferation marker Ki-67. In each case, a 200-cell count was performed to obtain the percentage of cells positive for these 2 markers. Results.—The percentage of cyclin D1–positive cells was significantly higher in papillary carcinomas (89% ± 18%; range, 53%–98%) than in papillomas (8% ± 7%; range, 0%–19%). This difference was highly statistically significant (P &lt; .0001). Although the difference in Ki-67 positivity between these 2 groups was also statistically significant (P = .01), separation of papillary carcinomas and papillomas by Ki-67 immunoreactivity was less clear because of overlapping values between groups: 13% ± 6%; range, 9% to 23% for papillary carcinomas versus 8% ± 2%; range, 6% to 12% for papillomas. Conclusions.—These results support the notion that cyclin D1 is a useful marker for distinguishing breast papillomas from papillary carcinomas. The marker Ki-67 is also helpful, but is less useful than cyclin D1, owing to the overlap in Ki-67 results in papillomas and papillary carcinomas.

scholarly journals  Pathological and immunohistochemical studies on rare cases of primary extragenital transmissible venereal tumours in the mammary gland

2012 ◽  
Vol 57 (No. 4) ◽  
pp. 198-206 ◽  
Author(s):  
K. Gupta ◽  
NK Sood
Keyword(s):  
Mammary Gland ◽  
Cyclin D1 ◽  
Oral Mucosa ◽  
Mammary Glands ◽  
Present Communication ◽  
Ki 67 ◽  
Male And Female ◽  
First Report ◽  
Immunohistochemical Studies

Transmissible venereal tumours (TVT) are normally seen on the genitalia of both male and female dogs, and at times may be observed on extra-genital sites such as lips, oral mucosa, and peritoneum, or in organs such as the tonsils, eye, liver, spleen, kidney, lung, and musculature. The present communication deals with two rare cases of primary extragenital TVT involving the mammary glands of dogs and their pathology and immunohistochemistry. The study indicated that apart from routinely used markers such as vimentin, p53, PCNA, Ki-67 and c-myc, the oncogenes Rb and cyclin D1 proved to be novel markers of TVT in dogs. To the authors&rsquo; knowledge, this is the first report of extra-genital mammary TVT in canines. &nbsp;

scholarly journals An Attenuated Adenovirus, ONYX-015, As Mouthwash Therapy for Premalignant Oral Dysplasia

2003 ◽  
Vol 21 (24) ◽  
pp. 4546-4552 ◽  
Author(s):  
Charles M. Rudin ◽  
Ezra E.W. Cohen ◽  
Vassiliki A. Papadimitrakopoulou ◽  
Sol Silverman ◽  
Wendy Recant ◽  
...  
Keyword(s):  
Cyclin D1 ◽  
Significant Proportion ◽  
Febrile Episode ◽  
Additional Patient ◽  
Oral Epithelium ◽  
Histologic Response ◽  
Ki 67 ◽  
Oral Dysplasia ◽  
Novel Approach ◽  
P53 Response

Purpose: Dysplastic lesions of the oral epithelium are known precursors of oral cancer. A significant proportion of oral dysplastic lesions have functional defects in p53 response pathways. The ONYX-015 adenovirus is selectively cytotoxic to cells carrying defects in p53-dependent signaling pathways. The current study sought to establish the feasibility and activity of ONYX-015 administered topically as a mouthwash to patients with clinically apparent and histologically dysplastic lesions of the oral mucosa.Patients and Methods: A total of 22 patients (19 assessable patients) were enrolled onto the study. ONYX-015 was administered on three different schedules to consecutive cohorts. Biopsies of the involved mucosa were performed to evaluate histologic response and changes in expression of putative markers of malignant potential, including p53, cyclin D1, and Ki-67. Serology was performed to measure antiadenoviral titers.Results: Histologic resolution of dysplasia was seen in seven (37%) of 19 patients, and the grade of dysplasia improved in one additional patient. The majority of responses were transient. No toxicity greater than grade 2 (febrile episode in one patient) was observed. Only one of seven patients demonstrated an increase in circulating antiadenoviral antibody titer while on therapy. Although responding and resistant lesions had similar mean p53 staining at baseline, histologic response correlated with a decrease in p53 positivity over time. Significant changes in cyclin D1 or Ki-67 were not observed. Viral replication was confirmed in two of three lesions examined.Conclusion: This novel approach to cancer prevention is tolerable, feasible, and has demonstrable activity.

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