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.

scholarly journals CD73+ CD127high Long-Term Memory CD4 T Cells Are Highly Proliferative in Response to Recall Antigens and Are Early Targets in HIV-1 Infection

2021 ◽  
Vol 22 (2) ◽  
pp. 912
Author(s):  
Nabila Seddiki ◽  
John Zaunders ◽  
Chan Phetsouphanh ◽  
Vedran Brezar ◽  
Yin Xu ◽  
...  
Keyword(s):  
T Cells ◽  
Peripheral Blood ◽  
Cd4 T Cells ◽  
Significant Proportion ◽  
Long Term Memory ◽  
Ki 67 ◽  
Memory Cd4 T Cells ◽  
Hiv 1

HIV-1 infection rapidly leads to a loss of the proliferative response of memory CD4+ T lymphocytes, when cultured with recall antigens. We report here that CD73 expression defines a subset of resting memory CD4+ T cells in peripheral blood, which highly express the α-chain of the IL-7 receptor (CD127), but not CD38 or Ki-67, yet are highly proliferative in response to mitogen and recall antigens, and to IL-7, in vitro. These cells also preferentially express CCR5 and produce IL-2. We reasoned that CD73+ memory CD4+ T cells decrease very early in HIV-1 infection. Indeed, CD73+ memory CD4+ T cells comprised a median of 7.5% (interquartile range: 4.5–10.4%) of CD4+ T cells in peripheral blood from healthy adults, but were decreased in primary HIV-1 infection to a median of 3.7% (IQR: 2.6–6.4%; p = 0.002); and in chronic HIV-1 infection to 1.9% (IQR: 1.1–3%; p < 0.0001), and were not restored by antiretroviral therapy. Moreover, we found that a significant proportion of CD73+ memory CD4+ T cells were skewed to a gut-homing phenotype, expressing integrins α4 and β7, CXCR3, CCR6, CD161 and CD26. Accordingly, 20% of CD4+ T cells present in gut biopsies were CD73+. In HIV+ subjects, purified CD73+ resting memory CD4+ T cells in PBMC were infected with HIV-1 DNA, determined by real-time PCR, to the same level as for purified CD73-negative CD4+ T cells, both in untreated and treated subjects. Therefore, the proliferative CD73+ subset of memory CD4+ T cells is disproportionately reduced in HIV-1 infection, but, unexpectedly, their IL-7 dependent long-term resting phenotype suggests that residual infected cells in this subset may contribute significantly to the very long-lived HIV proviral DNA reservoir in treated subjects.

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 Expression of Ki-67 in normal oral epithelium, leukoplakic oral epithelium and oral squamous cell carcinoma

2014 ◽  
Vol 18 (2) ◽  
pp. 169 ◽  
Author(s):  
SmitaShrishail Birajdar ◽  
MB Radhika ◽  
K Paremala ◽  
Mohsin Gadivan ◽  
M Sudhakara ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Oral Epithelium ◽  
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 Transhepatic echocardiography: a novel approach for imaging in left ventricle assist device patients with difficult acoustic windows

2020 ◽  
Vol 21 (5) ◽  
pp. 491-497 ◽  
Author(s):  
Mihai Strachinaru ◽  
Daniel J Bowen ◽  
Alina Constatinescu ◽  
Olivier C Manintveld ◽  
Jasper J Brugts ◽  
...  
Keyword(s):  
Left Ventricle ◽  
Significant Proportion ◽  
Left Ventricular ◽  
Assist Device ◽  
Novel Approach ◽  
Significant Difference ◽  
Inflow Cannula ◽  
Probe Orientation ◽  
And Function ◽  
Ventricle Assist Device

Abstract Aims A significant proportion of left ventricle assist device (LVAD) patients have very difficult transthoracic echocardiographic images. The aim of this study was to find an echocardiographic window which would provide better visualization of the heart in LVAD patients with limited acoustic windows. Methods and results Based on the anatomic relationships in LVAD patients, a right intercostal transhepatic approach was proposed. By using a computer simulator, we searched for the appropriate probe orientation. Further, 15 ambulatory LVAD patients (age 56 ± 15 years, 73% males) underwent two echocardiographic studies: one normal transthoracic echocardiography following the institutional protocol (Echo 1) and a second study which included the transhepatic approach (Echo 2). The two exams were performed by two different sonographers and the results validated by a third observer for agreement. The transhepatic intercostal window was feasible in all patients, with an image quality allowing good visualization of structures in 93%. Precise quantification of the left ventricular (LV) and right ventricular (RV) function was achieved more often in the Echo 2 (10 vs. 3 patients for LV, P = 0.03 and 14 vs. 8 patients for RV, P = 0.04). A significant difference existed also in the quantification of the LVAD inflow cannula flow by pulsed Doppler (11 patients in Echo 2 vs. 3 patients in Echo 1, P = 0.009). Conclusion This is the first study describing a new echocardiographic window in LVAD patients. The transhepatic window may provide better quantification of left and RV dimensions and function and improvement in Doppler interrogation of the inflow cannula.

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