A Presurgical Study of Curcumin Combined with Anthocyanin Supplements in Patients with Colorectal Adenomatous Polyps

Adenomatous polyps are precancerous lesions associated with a higher risk of colorectal cancer (CRC). Curcumin and anthocyanins have shown promising CRC-preventive activity in preclinical and epidemiological studies. The objective of this window-of-opportunity, proof-of principle trial was to evaluate the effect of curcumin combined with anthocyanin supplements on tissue biomarkers of colorectal adenomatous polyps. Eligible patients received either anthocyanin and curcumin supplementation or related matching placebo for 4–6 weeks before polyp removal. Adenomatous polyps and adjacent tissue biopsies were collected at baseline and after supplementation for immunohistochemical assessment of β-catenin, NF-kappa B (NF-κB), Ki-67, P53, and dysplasia. No differences were observed in baseline biomarker expression between normal and dysplastic tissues. The combination of anthocyanins and curcumin resulted in a significant borderline reduction of NF-κB immunohistochemistry (IHC) expression in adenoma tissue (geometric mean ratio (GMR): 0.72; 95% confidence interval (CI): 0.51–1.00; p-value: 0.05) and a trend to a reduction of Ki-67 (GMR: 0.73; 95% CI: 0.50–1.08; p-value: 0.11). No significant modulation of biomarkers in normal adjacent mucosa was observed. We concluded that the combined supplementation of anthocyanins and curcumin seems to lead to a potentially favorable modulation of tissue biomarkers of inflammation and proliferation in colon adenomas.

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The role of immunohistochemistry in the diagnosis of cervical intraepithelial neoplasia of different severity

HEALTH OF WOMAN ◽

10.15574/hw.2016.113.138 ◽

2016 ◽

pp. 138-140

Author(s):

S.I. Zhuk ◽

◽

O.A. Taran ◽

A.N. Koshmienskaya ◽

T.V. Lobastova ◽

...

Keyword(s):

Protein Expression ◽

Cervical Intraepithelial Neoplasia ◽

Precancerous Lesions ◽

Molecular Genetic ◽

Intraepithelial Neoplasia ◽

Reproductive Age ◽

Moderate Degree ◽

Ki 67 ◽

The Third ◽

Diagnosis And Prognosis

The objective: the finding of protein expression of apoptosis regulator BCL-2, Smooth Muscule Actin and the antigen Ki-67 in cervical intraepithelial neoplasia of different severity to optimize the diagnosis and prognosis of the disease. Patients and methods. The study involved 42 women of reproductive age with cervical intraepithelial the neoplasia of the cervix varying degrees applied to the doctor of cervical pathology Zhitomir regional oncologic dispensary. All women (n=42) were divided into groups. The first group included 15 patients (35.7%) with cervical intraepithelial neoplasia with mild. The second group included 13 women (31%) with cervical intraepithelial neoplasia a moderate degree. The third group was represented by patients with cervical intraepithelial neoplasia with severe – 14 respondents (33.3 per cent). Results. Marker BCL-2 in patients of the first group was positive in 7 patients (46.7%), Smooth Muscule Actin was positive in 9 patients (60%) and Ki-67 was diagnosed in 8 of the surveyed women (53.3%). In the second group of BCL-2 was positive in 8 patients (61.5%), Clone 124, Smooth Muscule Actin, Clone 1A4 was positive in 9 patients (69.2%), and Ki-67 was diagnosed in 12 of the surveyed women (92.3%). Marker BCL-2 in patients of the third group was positive in 12 patients (85.7%), Smooth Muscule Actin was positive in 10 patients (71.4%) and Ki-67 was diagnosed in 13 of the surveyed women (92.9% ). Conclusion. Carcinogenesis is associated with molecular genetic damage to the cervix. Some of the products of this process can be used as prognostic and diagnostic markers of tumor progression. Determination of protein expression of apoptosis regulator BCL-2, Smooth Muscule Actin and the antigen Ki-67 in cervical intraepithelial neoplasia makes it possible to accurately verify the diagnosis and to predict the course of pathological changes in the flat epithelium of the cervix. Key words: cervical intraepithelial neoplasia, cervical cancer, morphological diagnostics of precancerous lesions, BCL-2, Smooth Muscule Actin, Ki-67.

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Loss of Nitric Oxide Induces Fibrogenic Response in Organotypic 3D Co-Culture of Mammary Epithelia and Fibroblasts—An Indicator for Breast Carcinogenesis

Cancers ◽

10.3390/cancers13112815 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2815

Author(s):

Gang Ren ◽

Xunzhen Zheng ◽

Vandana Sharma ◽

Joshua Letson ◽

Andrea L. Nestor-Kalinoski ◽

...

Keyword(s):

Nitric Oxide ◽

Culture System ◽

Epithelial Mesenchymal Transition ◽

Precancerous Lesions ◽

Three Dimensional ◽

Epidemiological Studies ◽

Mesenchymal Transition ◽

In Vitro Response ◽

Mammary Epithelia

Excessive myofibroblast activation, which leads to dysregulated collagen deposition and the stiffening of the extracellular matrix (ECM), plays pivotal roles in cancer initiation and progression. Cumulative evidence attests to the cancer-causing effects of a number of fibrogenic factors found in the environment, diseases and drugs. While identifying such factors largely depends on epidemiological studies, it would be of great importance to develop a robust in vitro method to demonstrate the causal relationship between fibrosis and cancer. Here, we tested whether our recently developed organotypic three-dimensional (3D) co-culture would be suitable for that purpose. This co-culture system utilizes the discontinuous ECM to separately culture mammary epithelia and fibroblasts in the discrete matrices to model the complexity of the mammary gland. We observed that pharmaceutical deprivation of nitric oxide (NO) in 3D co-cultures induced myofibroblast differentiation of the stroma as well as the occurrence of epithelial–mesenchymal transition (EMT) of the parenchyma. Such in vitro response to NO deprivation was unique to co-cultures and closely mimicked the phenotype of NO-depleted mammary glands exhibiting stromal desmoplasia and precancerous lesions undergoing EMT. These results suggest that this novel 3D co-culture system could be utilized in the deep mechanistic studies of the linkage between fibrosis and cancer.

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To Determine the Degree of Agreement between Ki67 and Histopathology to Differentiate between Hydatidiform Mole

10.53350/pjmhs2115102619 ◽

2021 ◽

Vol 15 (10) ◽

pp. 2619-2621

Author(s):

Mariya Manzoor ◽

Haseeb Ahmed Khan ◽

Sabiha Riaz ◽

Imrana Tanvir ◽

Atiya Batool Gardezi ◽

...

Keyword(s):

Hydatidiform Mole ◽

P Value ◽

Kappa Statistics ◽

Cross Sectional Survey ◽

Ki 67 ◽

Cross Sectional ◽

Histopathologic Diagnosis ◽

Hematoxylin And Eosin ◽

High Degree ◽

Gross Examination

Aim: To determine the degree of agreement between Ki67 and histopathology to differentiate between hydatidiform mole and hydropic abortus. Methods: Descriptive, Cross Sectional Survey was conducted in the Department of Pathology, Fatima Memorial Hospital, Lahore during 6 months (May 11, 2016 to Nov 11, 2016). Using non-probability consecutive sampling, 105 cases were included in this study as per the inclusion and exclusion criteria. 10% buffered formalin was used to fix the sepecimens. Gross examination and staining with Hematoxylin and Eosin was done. The cases were diagnosed by a histopathologist. IHC staining Ki67 was performed, assessed by histopathologist and the data was recorded on the proforma. Results: The mean age was 27.79±5.81 years with minimum and maximum ages of 18 years and 42 years respectively. The histopathological findings showed hydatidiform mole in 41 (39%) women and hydropic abortus in 64(61%) women. The Ki67 was reported to be >25 in 41(39%) patients and less than or equal to 25 in 64(61%) patients. The agreement of differentiation in the two types for histopathology and Ki67 was found in 101(96.2%) patients. Kappa statistics showed 92% (p-value= 0.000) strength of agreement between histopathology and Ki67. Conclusion: There is high degree of agreement between Ki67 and histopathology for differentiation of hydatidiform mole and hydropic abortus. So Ki67 can be used as an adjacent in histopathologic diagnosis of hydatidiform mole in difficult cases. MeSh words: Hydatidiform Mole, Immunohistochemistry, Ki-67 Antigen

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Phase I Pharmacokinetic and Pharmacodynamic Study of the Oral, Small-Molecule Mitogen-Activated Protein Kinase Kinase 1/2 Inhibitor AZD6244 (ARRY-142886) in Patients With Advanced Cancers

Journal of Clinical Oncology ◽

10.1200/jco.2007.14.4956 ◽

2008 ◽

Vol 26 (13) ◽

pp. 2139-2146 ◽

Cited By ~ 432

Author(s):

Alex A. Adjei ◽

Roger B. Cohen ◽

Wilbur Franklin ◽

Clive Morris ◽

David Wilson ◽

...

Keyword(s):

Protein Kinase ◽

Phase Ii ◽

Geometric Mean ◽

Mitogen Activated Protein Kinase ◽

Cancer Type ◽

Ki 67 ◽

Phase Ii Studies ◽

Erk Phosphorylation ◽

Mitogen Activated Protein ◽

Protein Kinase Kinase

Purpose To assess the tolerability, pharmacokinetics (PKs), and pharmacodynamics (PDs) of the mitogen-activated protein kinase kinase (MEK) 1/2 inhibitor AZD6244 (ARRY-142886) in patients with advanced cancer. Patients and Methods In part A, patients received escalating doses to determine the maximum-tolerated dose (MTD). In both parts, blood samples were collected to assess PK and PD parameters. In part B, patients were stratified by cancer type (melanoma v other) and randomly assigned to receive the MTD or 50% MTD. Biopsies were collected to determine inhibition of ERK phosphorylation, Ki-67 expression, and BRAF, KRAS, and NRAS mutations. Results Fifty-seven patients were enrolled. MTD in part A was 200 mg bid, but this dose was discontinued in part B because of toxicity. The 50% MTD (100 mg bid) was well tolerated. Rash was the most frequent and dose-limiting toxicity. Most other adverse events were grade 1 or 2. The PKs were less than dose proportional, with a median half-life of approximately 8 hours and inhibition of ERK phosphorylation in peripheral-blood mononuclear cells at all dose levels. Paired tumor biopsies demonstrated reduced ERK phosphorylation (geometric mean, 79%). Five of 20 patients demonstrated ≥ 50% inhibition of Ki-67 expression, and RAF or RAS mutations were detected in 10 of 26 assessable tumor samples. Nine patients had stable disease (SD) for ≥ 5 months, including two patients with SD for 19 (thyroid cancer) and 22 (uveal melanoma plus renal cancer) 28-day cycles. Conclusion AZD6244 was well tolerated with target inhibition demonstrated at the recommended phase II dose. PK analyses supported twice-daily dosing. Prolonged SD was seen in a variety of advanced cancers. Phase II studies are ongoing.

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Expression of HER2/neu and Ki-67 in Urothelial Carcinoma and their Relation to Clinicopathological Data: An Egyptian Study

JOURNAL FOR CLINICAL AND DIAGNOSTIC RESEARCH ◽

10.7860/jcdr/2021/45922.14624 ◽

2021 ◽

Author(s):

Badawia B Ibrahim ◽

Samira A Mahmoud ◽

Alzahraa A Mohamed ◽

Hala M El Hanbuli

Keyword(s):

Urothelial Carcinoma ◽

Bladder Carcinoma ◽

Histological Grade ◽

P Value ◽

Urinary Bladder Carcinoma ◽

Ki 67 ◽

Urothelial Bladder Carcinoma ◽

Cellular Marker ◽

Urothelial Bladder ◽

Common Malignancy

Introduction: Bladder cancer is the most common malignancy involving the urinary system and the ninth most common malignancy worldwide. Ki-67 is a nonhistone cellular marker for proliferation. HER2/neu is an oncogene that plays an important role in the pathogenesis of many cancer types. In bladder carcinoma, its clinical significance remains under-investigated and poorly linked to the patients’ clinicopathological features especially with no reported Egyptian study. Aim: The aim of this work was to study the expression of HER2/neu and Ki-67 in urinary bladder carcinoma to evaluate their role in tumourigenesis and their correlation with other available clinicopathological variables associated with urothelial carcinoma. Materials and Methods: This cross-sectional study was conducted at the Department of Pathology, Faculty of Medicine, Cairo University, Egypt. Samples were paraffin blocks from 60 cases diagnosed with urothelial carcinoma underwent radical cystectomy. Ki-67 and HER2/neu immunohistochemical staining was done and of Ki-67 and HER2/neu Immunostaining was recorded. The associations between Ki-67, HER2/neu expressions and clinical and histopathological parameters of urothelial bladder carcinoma was evaluated. Results: The Ki-67 expression had significant association with tumour histological grade and lymphovascular invasion (p-value <0.05). The association of HER2/neu expression had significant association with perineural invasion (p-value <0.05). Conclusion: HER2/neu immunostaining was not associated with most of the clinicopathologic prognostic factors in urothelial bladder carcinoma.

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Evaluation of PTEN and Ki67 Expression in Typical and Atypical Endometriosis and Endometriosis Associated Ovarian Cancer

Shiraz E-Medical Journal ◽

10.5812/semj.99291 ◽

2020 ◽

Vol 21 (11) ◽

Author(s):

Mojgan Akbarzadeh-Jahromi ◽

Zahra Zare ◽

Fatemeh Sari Aslani ◽

Simin Torabinezhad

Keyword(s):

Ovarian Cancer ◽

Precancerous Lesion ◽

Early Event ◽

P Value ◽

Ovarian Endometriosis ◽

Ki 67 ◽

Pten Loss ◽

Epithelial Component ◽

Increased Risk ◽

Atypical Endometriosis

Background: Several studies reported that endometriosis is associated with an increased risk of ovarian cancer. Atypical endometriosis is common in patients with endometriosis-associated ovarian, which might be considered as a precancerous lesion. Objectives: This study aimed to assess ki67 and PTEN expression in endometriosis associated ovarian cancer (EAOC), atypical endometriosis, and typical endometriosis. Methods: In this study, all H & E slides of 260 ovarian endometriosis cases were reviewed. And 25 cases were diagnosed with atypical endometriosis. Forty-one typical endometrioses and 24 ovarian cancers with endometriosis were included. We assessed PTEN and Ki67 immunoexpression in epithelial and stromal cells. Results: The prevalence of atypical endometriosis was about 9%. PTEN loss was found in 12 (out of 24 or 50%) of EAOC, 2 (out of 25; 8%) of atypical endometriosis, and none of the typical endometriosis. In all 12 PTEN loss cases, the PTEN loss pattern in endometriosis adjacent to ovarian cancer was similar to that of ovarian cancer. A total of 7.3% of typical endometriosis and 8% atypical endometriosis and 33.3% of EAOC had Ki67 staining in more than 50% of the epithelial component. Both typical and atypical endometriosis showed similar PTEN loss and Ki 67 staining (in more than 50% of the epithelial component) (P value > 0.05), and both of them were different from EAOC (P value < 0.05). Conclusions: The PTEN loss pattern in endometriosis adjacent to ovarian cancer was similar to that of ovarian cancer. The result indicated that PTEN loss could be an early event in the tumor development pathway from endometriosis to ovarian cancer.

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Childhood Estimates of Glomerular Filtration Rate Based on Creatinine and Cystatin C: Importance of Body Composition

American Journal of Nephrology ◽

10.1159/000463395 ◽

2017 ◽

Vol 45 (4) ◽

pp. 320-326 ◽

Cited By ~ 6

Author(s):

Kozeta Miliku ◽

Hanneke Bakker ◽

Eiske M. Dorresteijn ◽

Karlien Cransberg ◽

Oscar H. Franco ◽

...

Keyword(s):

Body Composition ◽

Glomerular Filtration Rate ◽

Glomerular Filtration ◽

Cystatin C ◽

Fat Mass ◽

Filtration Rate ◽

Epidemiological Studies ◽

Population Based ◽

P Value ◽

Blood Concentrations

Background: Creatinine and cystatin C concentrations are commonly used to estimate glomerular filtration rate (eGFR) in clinical practice and epidemiological studies. To estimate the influence of different body composition measures on eGFR from creatinine and cystatin C blood concentrations, we compared the associations of different anthropometric and body composition measures with eGFR derived from creatinine (eGFRcreat) and cystatin C (eGFRcystC) blood concentrations. Methods: In a population-based cohort study among 4,305 children aged 6.0 years (95% range 5.7-8.0), we measured weight and height and calculated body mass index (BMI) and body surface area (BSA), and lean and fat mass using dual-energy X-ray absorptiometry. At the same age, we measured creatinine and cystatin C blood concentrations and estimated the GFR. Results: Correlation between eGFR based on creatinine and cystatin C concentrations was r = 0.40 (p value <0.01). Higher BMI was associated with lower eGFRcystC but not with eGFRcreat. Higher BSA was associated with higher eGFRcreat and lower eGFRcystC (p value <0.05). Lean and fat mass percentages were associated with eGFRcreat but not with eGFRcystC. Conclusion: Our findings suggest that both eGFRcreat and eGFRcystC are influenced by BMI and BSA. eGFRcreat is more strongly influenced by body composition than eGFRcystC.

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Weipiling ameliorates gastric precancerous lesions in Atp4a−/− mice

BMC Complementary and Alternative Medicine ◽

10.1186/s12906-019-2718-y ◽

2019 ◽

Vol 19 (1) ◽

Author(s):

Wei Liu ◽

Zi-ming Zhao ◽

Yuan-liang Liu ◽

Hua-feng Pan ◽

Li-zhu Lin

Keyword(s):

Gastric Mucosa ◽

Precancerous Lesions ◽

Tunel Staining ◽

Model Group ◽

Ki 67 ◽

Protein Levels ◽

Chinese Medicine Formula ◽

Pas Staining ◽

Different Doses

Abstract Background Altered cellular metabolism is considered to be one of the hallmarks of cancer (Coller, Am J Pathol 184:4–17, 2014; Kim and Bae, Curr Opin Hematol 25:52–59, 2018). However, few studies have investigated the role of metabolism in the development of gastric precancerous lesions (GPLs). Weipiling (WPL), a traditional Chinese medicine formula for treatment of GPLs. In this study, we evaluated the amelioration of GPLs by WPL and investigated the possible role of WPL in regulating glucose metabolism. Methods Firstly, the major components of WPL are chemically characterized by HPLC analytical method. In this study, we chose the Atp4a−/− mouse model (Spicer etal., J Biol Chem 275:21555–21565, 2000) for GPL analysis. Different doses of WPL were administered orally to mice for 10 weeks. Next, the pathological changes of gastric mucosa were assessed by the H&E staining and AB-PAS staining. In addition, TUNEL staining was used to evaluate apoptosis, and we further used immunohistochemically labelled CDX2, MUC2, ki-67, PTEN, and p53 proteins to assess the characteristic changes of gastric mucosa in precancerous lesions. The levels of such transporters as HK-II, PKM2, ENO1, MPC1, and LDHA were determined by Western blot analysis. Finally, we assessed the expression of mTOR, HIF-1α, AMPK, Rheb, TSC1 and TSC2 protein in the gastric mucosa of Atp4a−/−mice. Results In this work, we evaluated the protective effect of WPL on gastric mucosa in mice with precancerous lesions. The aberrant apoptosis in gastric mucosa of gastric pre-cancerous lesions was controlled by WPL (P<0.05). Furthermore, WPL suppressed the expression of CDX2, MUC2, ki-67, PTEN and p53, as the levels of these proteins decreased significantly compared with the model group (P<0.05). In parallel, WPL significantly suppressed the expression of transporters, such as HK-II, PKM2, ENO1, MPC1 and LDHA (P<0.05). In addition, mTOR, HIF-1a, AMPK, Rheb, TSC1 and TSC2 protein levels in gastric mucosa of Atp4a−/− mice in the high- and low-dose WPL groups were significantly lower than those in the model group (P<0.05), while the expression of TSC1 and TSC2 protein was significantly higher (P<0.05). Conclusions Conclusively, WPL could ameliorate GPLs in Atp4a−/− mice by inhibiting the expression of transporters and suppressing the aberrant activation of mTOR/HIF-1α.

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Role of p16/INK4a and Ki-67 as specific biomarkers for cervical intraepithelial neoplasia: An institutional study

Journal of Laboratory Physicians ◽

10.4103/0974-2727.199630 ◽

2017 ◽

Vol 9 (02) ◽

pp. 104-110 ◽

Cited By ~ 1

Author(s):

Ankitha Hebbar ◽

Venkataramappa Srinivasa Murthy

Keyword(s):

Diagnostic Accuracy ◽

Cervical Intraepithelial Neoplasia ◽

Squamous Metaplasia ◽

Intraepithelial Neoplasia ◽

P Value ◽

Kappa Statistics ◽

Histopathological Diagnosis ◽

Ki 67 ◽

Cervical Biopsy ◽

P16 Ink4a

Abstract BACKGROUND: P16/INK4a and Ki-67 have emerged as important biomarkers for the detection of high-risk human papilloma virus (HR-HPV) associated dysplastic changes in the cervical biopsy samples. The increasing inter- and intra-observer variability in the diagnosis of dysplastic lesions and immature squamous metaplasia on histopathology has led to the advent of these biomarkers. This study was taken up with an aim to study their role in increasing the diagnostic accuracy in equivocal cases on histopathology. MATERIALS AND METHODS: Fifty cervical biopsy specimens were stained with p16/INK4a and Ki-67 consisting of 10 cases each of cervical intraepithelial neoplasia (CIN I/II/III) along with five cases of squamous metaplasia. Histopathological diagnosis was considered as the gold standard. Statistical analysis was done by kappa statistics, and P value was calculated. RESULTS: The sensitivity and specificity of p16/INK4a and Ki-67 were 76.2%, 87.5%, 90.5%, and 87.5%, respectively. The overall agreement of both the immunostains with histopathological diagnosis was statistically significant (P < 0.05) and the diagnostic accuracy improved when both the stains were used in conjunction. CONCLUSION: Ki-67 and p16/INK4a can be used as complimentary tests in differentiating dysplastic and nondysplastic lesions and help in confirming the histopathological diagnosis. They aid in recognition of dysplasias caused by HR-HPV, which have higher tendency to progress to neoplasia. However, further research is advocated before the widespread use of these markers for screening of dysplasias.

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Surface Ki-67 Expression Improves Reproducibility of Dysplasia Diagnosis in Barrett’s Esophagus

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqaa004 ◽

2020 ◽

Vol 153 (5) ◽

pp. 695-704 ◽

Cited By ~ 1

Author(s):

Hira Yousaf ◽

Umar Hayat ◽

Juan Manivel ◽

Carlos Iwamoto ◽

Justin Peltola ◽

...

Keyword(s):

Barrett’S Esophagus ◽

Barrett's Esophagus ◽

Case Control Study ◽

Expression Patterns ◽

Cell Interaction ◽

P Value ◽

Ki 67 ◽

Diagnostic Categories ◽

Glass Slides ◽

Control Study

Abstract Objectives Many studies have shown poor reproducibility among pathologists for diagnosing dysplasia in Barrett’s esophagus (BE). Immunohistochemical stains (IHC) are not widely used due to overlapping expression patterns in reactive and dysplastic processes. We hypothesized that markers involved in cell-cycle (cyclin D1, Ki-67, P16), differentiation/cell-cell interaction (β-catenin, SATB2 CD44, OCT4) and senescence (γH2AX) would produce different results in reactive and dysplastic processes. Methods A micrograph album of 40 H&E and matching IHCs depicting optimally oriented lesions were evaluated independently by 3 pathologists. Expression was scored separately in the surface, isthmus, and base regions of the glands. Results Statistical analysis showed that surface Ki-67 expression showed the largest difference in expression and smallest P value (P < .001) for identifying dysplasia. At a cutoff level of 5% or less, negative predictive value (NPV) was 100%. κ correlation between pathologists improved from substantial to almost perfect (0.70-0.95) using ancillary surface Ki-67. Conclusion A case-control study with glass slides including all diagnostic categories using this parameter confirmed improved κ correlation among pathologists (0.29 vs 0.60), better correlation with outcomes (76% vs 69%), increased odd risks (15.3) for progression in positive cases, and an improvement in sensitivity (88% vs 64%) and NPV (88% vs 73%) compared to histology alone.

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