• Biomedical Science Letters
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• v.16 no.4
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• pp.307-310
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• 2010

Apoptosis is an important significance in the pathogenesis of cancer. Caspase 3 and p53 have been identified as important members of the apoptosis related proteins. This study was performed to define roles of caspase 3 expression and its relationship with p53 expression in endometrial cancers by immunohistochemistry. Immunoreactivity for caspase 3 was found in 13 (65.0%) out of 20 endometrial hyperplasia cases and 8 (36.4%) out of 22 endometrial cancers. Seven (87.5%) of the 8 cases with a positive caspase 3 immunoreactivity showed a positive p53 expression in 22 endometrial cancers. There were no significant associations between caspase 3 and p53 expressions. These findings suggest that caspase 3 expression might be associated with carcinogenesis of endometrial cancers. Further studies are needed to define the relationship between caspase 3 and p53 and apoptosis for examining the mechanisms of tissue-specific apoptosis related protein.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.977-980
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• 2013

Background: Endometrial cancer is common in western women, and the rates are very high; however in India, the rates are as low as 4.3 per 100,000 (Delhi). Objective: To estimate the survival of endometrial cancer patients based on age, education, family history, tobacco habit, number of pregnancies, clinical extent of disease and treatment received. Materials and Methods: The present retrospective study was carried out at the Tata Memorial Hospital (TMH), Mumbai, India, between 1999-2002. 310 cases treated in TMH were considered as eligible entrants for the study. Five-year survival rates were estimated using actuarial and loss-adjusted (LAR) methods. Results: The proportions of patients dying above 50 years of age, non-residents and illiterates was higher than their counterparts. 54.8% of patients had some form of treatment before attending TMH. There were only 4.2% tobacco-chewers and only 6.1% had a family history of cancer. There were 25.8% who had 3-5 pregnancies (not living children) and 38.1% did not remember the pregnancy history. The 5-year overall survival rate was 92%. The five-year rates indicated better prognosis for those aged less than 50 years (97%), non-tobacco-chewers (94%), with no family history of cancer (93%), with localized disease (93%) and those treated with surgery either alone or as a combination treatment (95%). Conclusions: The present study showed that endometrial cancer patients with localized disease at diagnosis have a good outcome in India. A detailed study will help in understanding the prognostic indicators for survival especially with the newer treatment technologies now available.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10067-10070
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• 2015

Background: Unopposed estrogen has a central role in development of endometrial benign, premalignant and malignant lesions. The aim of this study was to evaluate the anti-estrogenic effect of metformin on endometrial histology in comparison with progesterone. Materials and Methods: A total of 43 patients who were referred to our center for abnormal uterine bleeding and had a histologic diagnosis were disordered proliferative endometrium or simple endometrial hyperplasia were included and randomly distributed in two groups treated with metformin (500mg Bid) or megestrol (40mg daily), respectively, for three months. After this period the patients were evaluated by another endometrial biopsy to assess the impact of the two drugs in restoring normal endometrial histology. Results: Our findings revealed that metformin could induce endometrial atrophy in 21 out of 22 patients (95.5%) while this positive response was achieved in only 13 out of 21 patients (61.9%) in the megstrol group. In addition two low grade endometrial carcinomas in the metformin group responded very well. Conclusions: We conclude that metformin could be used as an effective antiestrogenic agent in control of abnormal endometrial proliferative disorders.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5589-5597
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• 2013

The aim of this review article was to evaluate the relationship and the possible etiological mechanisms between endometriosis, leiomyoma (LM) and adenomyosis and gynecological cancers, such as ovarian and endometrial cancer and leiomyosarcoma (LMS). MEDLINE was searched for all articles written in the English literature from July 1966 to May 2013. Reports were collected systematically and all the references were also reviewed. Malignant transformation of gynecologic benign diseases such as endometriosis, adenomyosis and LM to ovarian and endometrial cancer remains unclear. Hormonal factors, inflammation, familial predisposition, genetic alterations, growth factors, diet, altered immune system, environmental factors and oxidative stress may be causative factors in carcinogenesis. Early menarche, low parity, late menopause and infertility have also been implicated in the pathogenesis of these cancers. Ovarian cancers and endometriosis have been shown to have common genetic alterations such as loss of heterozygosity (LOH), PTEN, p53, ARID1A mutations. MicroRNAs have also been implicated in malignant transformation. Inflammation releases proinflammatory cytokines, and activates tumor associated macrophages (TAMS) and nuclear factor kappa b (NF-KB) signaling pathways that promote genetic mutations and carcinogenesis. MED12 mutations in LM and smooth muscle tumors of undetermined malignant potential (STUMP) may contribute to malignant transformation to LMS. A hyperestrogenic state may be shared in common with pathogenesis of adenomyosis, LM and endometrial cancer. However, the effect of these benign gynecologic diseases on endometrial cancer should be studied in detail. This review study indicates that endometriosis, LM, adenomyosis may be associated with increased risk of gynecological cancers such as endometrial and ovarian cancers. The patients who have these gynecological benign diseases should be counseled about the future risks of developing cancer. Further studies are needed to investigate the relationship between STUMPs, LMS and LM and characteristics and outcome endometrial carcinoma in adenomyotic patients.

• Journal of Animal Reproduction and Biotechnology
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• v.35 no.1
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• pp.35-41
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• 2020

In this study, we investigated whether infusion of colorectal cancer cell line and PMSG could increase endometrial cancer. As a result, our study confirmed that the injection of colorectal cancer can cause inflammation and cancer in the uterus and increase the VEGF gene in the uterus. The study also found that endometrial cancer was associated with PMSG.

• Biomolecules & Therapeutics
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• v.29 no.6
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• pp.650-657
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• 2021

Metformin is an anti-diabetic drug and has anticancer effects on various cancers. Several studies have suggested that metformin reduces cell proliferation and stimulates cell-cycle arrest and apoptosis. However, the definitive molecular mechanism of metformin in the pathophysiological signaling in endometrial tumorigenesis and metastasis is not clearly understood. In this study, we examined the effects of metformin on the cell viability and apoptosis of human cervical HeLa and endometrial HEC-1-A and KLE cancer cells. Metformin suppressed cell growth in a dose-dependent manner and dramatically evoked apoptosis in HeLa cervical cancer cells, while apoptotic cell death and growth inhibition were not observed in endometrial (HEC-1-A, KLE) cell lines. Accordingly, the p27 and p21 promoter activities were enhanced while Bcl-2 and IL-6 activities were significantly reduced by metformin treatment. Metformin diminished the phosphorylation of mTOR, p70S6K and 4E-BP1 by accelerating adenosine monophosphate-activated kinase (AMPK) in HeLa cancer cells, but it did not affect other cell lines. To determine why the anti-proliferative effects are observed only in HeLa cells, we examined the expression level of liver kinase B1 (LKB1) since metformin and LKB1 share the same signalling system, and we found that the LKB1 gene is not expressed only in HeLa cancer cells. Consistently, the overexpression of LKB1 in HeLa cancer cells prevented metformin-triggered apoptosis while LKB1 knockdown significantly increased apoptosis in HEC-1-A and KLE cancer cells. Taken together, these findings indicate an underlying biological/physiological molecular function specifically for metformin-triggered apoptosis dependent on the presence of the LKB1 gene in tumorigenesis.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.2
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• pp.497-501
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• 2016

Aim: To evaluate the relationship between pre-operative CA-125 levels and myometrial invasion in patients with early-stage endometrioid-type endometrial cancer. Materials and Methods: Two-hundred and sixty patients were diagnosed with endometrial cancer between January 2007 and December 2012. Of these, 136 patients with stage 1 endometrioid histologic-type and documented pre-operative serum CA-125 levels were included in the study. Age, preoperative CA-125 level, histologic grade, surgical grade, and presence of deep myometrial invasion were recorded. Additionally, 16, 20, and 35 IU/ml cutoff values were used and compared to evaluate the relationship between pre-operative CA-125 levels and myometrial invasion. Results: The average serum CA-125 level was $35.4{\pm}36.7$ in patients with deep myometrial invasion, and $21.5{\pm}35.8$ in cases without deep myometrial invasion. The relationship between the presence of deep myometrial invasion and CA-125 cut-off values (16, 20, 35 IU/ml) was statistically significant, although the correlation was weak (p<0.05). When the relationship between 16, 20 and 35 IU/ml CA-125 cut-off values and the presence of deep myometrial invasion was studied, specifity and sensitivity values were identified as: 0.60-0.68 for 16 IU/ml; 0.73-0.48 for 20 IU/ml; and 0.89-0.33 for 35 IU/ml. The sensitivity of 16 IU/ml cut-off value was higher when compared to other values. Conclusions: This study demonstrates that preoperative serum CA-125 values maybe used as a predictive test in patients with early stage endometrioid-type endometrium cancer, and as a prognostic factor alone. Further studies should be conducted to identify different CA-125 cut-off values in patients with low risk endometrial cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.7267-7270
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• 2015

Introduction: Kelantan is one of the states in Malaysia which has a high prevalence of type 2 diabetes (DM2). Other than with endometrial carcinoma, the association of DM2 with particular female cancers is not known. Objective: To determine the proportion of breast, cervical, ovarian and endometrial cancers among females with DM2 diagnosed in Hospital Universiti Sains Malaysia (HUSM) over an 11 year period. Materials and Methods: All histologically confirmed cases of breast, endometrial, cervical and ovarian carcinomas admitted to the Hospital were included in the study. The patient diabetic status was traced from the hospital medical records. Results: There was a total of 860 cases of breast, cervical, ovarian and endometrial carcinomas over this period. Breast carcinoma was the commonest, accounting for 437/860 (50.8%) followed by cervix, 159/860 (18.5%), ovarian, 143/860 (16.6%) and endometrial carcinomas, 121/860 (14.1%). Out of these, 228/860 (26.5%) were confirmed diabetics. Endometrial carcinoma patients showed the highest proportion being diabetics, 42.1% (51/121), followed by ovarian cancer, 25.9% (37/143), breast carcinoma, 23.6% (103/437) and cervical cancer 23.3% (37/159). Conclusions: There is a significant proportion of DM2 among women with these four cancers, endometrial carcinoma being the highest followed by ovarian, breast and cervical carcinoma. The rising trend of these four cancers is in tandem with an increasing trend of DM2 in the community. In populations where diabetes is prevalent, screening for epithelial cancers should be rigourous. Diabetic clinics should include screening for these cancers among their female patients and gynecology clinics should screen the women they treat for their diabetes status.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.11
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• pp.4521-4524
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• 2015

Background: Endometrial carcinoma is the most common malignant tumor of the female genital tract and the fourth most common cancer in Iranian women after breast, colorectal and lung cancers. Various genetic alterations appear to be early events in the pathogenesis of endometrial carcinoma and it seems that PTEN is the most commonly mutated gene in the endometrioid subtype. The aim of the present study was to investigate the correlation between mutations in exon 7 of PTEN gene and endometrial carcinoma. Materials and Methods: Seventy-five patients with endometrial carcinoma and 75 females whose underwent hysterectomy for non tumoral indication were selected for evaluation of PTEN mutations in exon 7 by PCR-SSCP and sequencing. Correlations between the frequency and type of mutation and the pathologic findings of the cancer (tumor subtype, stage and grade) were assessed. Results: All of the samples were obtained from Iranian patients. 60 % (45 cases) of the tumors were endometriod and 40% (30 cases) were of serous type. The grade distributions of the 75 cases according to the FIGO staging system were as follows: low grade, 20 cases; high grade 55 cases, low stage, 41 cases; high stage 34 cases. For exon 7 of the PTEN gene, the analysis showed that there were no mutations in our cases. Conclusions: Our findings in the present study suggest that exon 7 of PTEN does not play any significant role in the development of endometrial carcinoma in Iranian cases.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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• pp.9405-9410
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• 2014

Purpose: To evaluate the prognostic impact of peritoneal washing cytology in patients with endometrial and ovarian cancers. Materials and Methods: We retrospectively identified 86 individuals with ovarian carcinomas, ovarian borderline tumors and endometrial adenocarcinomas. The patients had been treated at Shahid Sadoughi Hospital and Ramazanzadeh Radiotherapy Center, Yazd, Iran between 2004 and 2012. Survival differences were determined by Kaplan-Meier analysis. Multivariate analysis was performed using the Cox regression method. A p<0.05 value was considered statistically significant. Results: There were 36 patients with ovarian carcinomas, 4 with borderline ovarian tumors and 46 with endometrial carcinomas. The mean age of the patients was $53.8{\pm}15.2years$. In patients with ovarian carcinoma the overall survival in the negative cytology group was better than the patients with positive cytology although this difference failed to reach statistical significance (p=0.30). At 0 to 50 months the overall survival was better in patients with endometrial adenocarcinoma and negative cytology than the patients with positive cytology but then it decreased (p=0.85). At 15 to 60 months patients with FIGO 2009 stage IA-II endometrial andocarcinoma and negative peritoneal cytology had a superior survival rate compared to 1988 IIIA and positive cytology only, although this difference failed to reach statistical significance(p=0.94). Multivariate analysis using Cox proportional hazards model showed that stage and peritoneal cytology were predictors of death. Conclusions: Our results show good correlation of peritoneal cytology with prognosis in patients with ovarian carcinoma. In endometrial carcinoma it had prognostic importance. Additional research is warranted.