Fulminant haemorrhage in cervical cancer leads to severe anaemia and haemodynamic instability. Palliative management includes vaginal packing as temporary measure, radiotherapy and other invasive surgical procedures. High dose emergency chemotherapy is not commonly implemented particularly when complicated with anaemia and renal impairment. We discuss three case series on the usefulness of high dose chemotherapy to combat bleeding from cervical cancer as an emergency treatment. The first case was clinically staged as operable 2A disease with severe anaemia due to bleeding from the tumour mass. The haemoglobin was corrected by blood transfusion while the bleeding was being arrested by high dose chemotherapy. The second case was inoperable with invasion to the bladder mucosa. She had frank haematuria and bleeding from the tumour with severe anaemia. A course of chemotherapy and blood transfusion controlled the bleeding and anaemia was corrected. The third case presented late with obstructive uropathy and anaemia. She required dialysis, blood transfusion and high dose emergency chemotherapy to stop the bleeding before undergoing urinary diversion after an unsuccessful ureteric stenting. High dose chemotherapy consisting cisplatin, vincristine, bleomycin and mitomycin-C has a clinical value in arresting fulminant haemorrhage in cervical cancer.
The present study was conducted to assess utility of p16(INK4a) immunopositivity as a surrogate marker for genomic integration of high-risk human papillomavirus infection (hrHPV). A total of 29 formalin-fixed, paraffin-embedded cervical low-grade squamous intraepithelial lesions (LSILs), 27 high-grade squamous intraepithelial lesions (HSILs) and 53 invasive squamous cell carcinomas (SCCs), histologically-diagnosed between 1st January 2006 to 31st December 2008 at the University of Malaya Medical Centre were stained for p16(INK4a) (CINtec Histology Kit (REF 9511, mtm laboratories AG, Heidelberg, Germany). Immunopositvity was defined as diffuse staining of the squamous cell cytoplasm and or nucleus (involving > 75% of the intraepithelial lesions or SCCs). Staining of basal and parabasal layers of intraepithelial lesions was pre-requisite. One (3.4%) LSIL, 24 (88.9%) HSIL and 46 (86.8%) SCC were p16(INK4a) immunopositive. All normal squamous epithelium did not express p16(INK4). p16(INK4a) expression was significantly lower (p<0.05) in LSIL compared with HSIL and SCC with no difference in expression between HSIL and SCC.The increased p16(INK4a) immunopositivity in HSIL and SCC appears in line with the integrated existence of the hrHPV and may provide more insightful information on risk of malignant transformation of cervical squamous intraepithelial lesions than mere hrHPV detection.
Interleukin-6 is one of the factors affecting sensitivity to cytotoxic agents. Therefore, the current study was designed to investigate the role of IL-6 and IL6 receptors in the cytotoxic effects of zerumbone in ovarian and cervical cancer cell lines (Caov-3 and HeLa, respectively). Exposure of both cancer cells to zerumbone or cisplatin demonstrated growth inhibition at a dose-dependent manner as determined by the MTT (3-[4,5-dimethylthiazol-2-yl]-2,Sdiphenyltetrazolium bromide) reduction assay. Both laser scanning confocal microscopy and TUNEL assay showed typical apoptotic features in treated cells. The studies conducted seems to suggest that zerumbone induces cell death by stimulating apoptosis better than cisplatin, based on the significantly higher percentage of apoptotic cells in zerumbone's treated cancer cells as compared to cisplatin. In addition, zerumbone and cisplatin arrest cancer cells at G2/M phase as analyzed by flow cytometry. Our results indicated that zerumbone significantly decreased the levels of IL-6 secreted by both cancer cells. In contrast, HeLa and Caov-3 cells were still sensitive to cisplatin and zerumbone, even in the presence of exogenous IL-6. However, membrane-bound IL-6 receptor is still intact after zerumbone treatment as demonstrated using an immune-fluorescence technique. This study concludes that the compound, zerumbone inhibits both cancer cell growth through the induction of apoptosis, arrests cell cycle at G2/M phase and inhibits the secretion levels of IL-6 in both cancer cells. Therefore, zerumbone is a potential candidate as a useful chemotherapeutic agent in treating both cervical and ovarian cancers in future.
We investigate induction of apoptosis by xanthohumol on Ca Ski cervical cancer cell line. Xanthohumol is a prenylated chalcone naturally found in hop plants, previously reported to be an effective anticancer agent in various cancer cell lines. The present study showed that xanthohumol was effective to inhibit proliferation of Ca Ski cells based on IC50 values using sulforhodamine B (SRB) assay. Furthermore, cellular and nuclear morphological changes were observed in the cells using phase contrast microscopy and Hoechst/PI fluorescent staining. In addition, 48-hour long treatment with xanthohumol triggered externalization of phosphatidylserine, changes in mitochondrial membrane potential, and DNA fragmentation in the cells. Additionally, xanthohumol mediated S phase arrest in cell cycle analysis and increased activities of caspase-3, caspase-8, and caspase-9. On the other hand, Western blot analysis showed that the expression levels of cleaved PARP, p53, and AIF increased, while Bcl-2 and XIAP decreased in a dose-dependent manner. Taken together, these findings indicate that xanthohumol-induced cell death might involve intrinsic and extrinsic apoptotic pathways, as well as downregulation of XIAP, upregulation of p53 proteins, and S phase cell cycle arrest in Ca Ski cervical cancer cells. This work suggests that xanthohumol is a potent chemotherapeutic candidate for cervical cancer.
A gene sensor for rapid detection of the Human Papillomavirus 16 (HPV 16) which is associated with the appearance of cervical cancer was developed. The assay is based on voltammetric determination of HPV 16 DNA by using interdigitated electrodes modified with titanium dioxide nanoparticles. Titanium dioxide nanoparticles (NPs) were used to modify a semiconductor-based interdigitated electrode (IDE). The surface of the NPs was then functionalized with a commercial 24-mer oligomer DNA probe for HPV 16 that was modified at the 5' end with a carboxyl group. If the probe interacts with the HPV 16 ssDNA, the current, best measured at a working voltage of 1.0 V, increases. The gene sensor has has a ∼ 0.1 fM limit of detection which is comparable to other sensors. The dielectric voltammetry analysis was carried out from 0 V to 1 V. The electrochemical sensitivity of the IDE is 2.5 × 10-5 μA·μM-1·cm-2. Graphical abstract Schematic of an interdigitated electrode (IDE) modified with titanium dioxide nanoparticles for voltammetric determination of HPV 16 DNA by using an appropriate DNA probe.
Well differentiated villoglandular adenocarcinoma of uterine cervix is a rare tumour which usually occurs in young women. It is considered to be an indolent tumour with favorable prognosis and most of them were treated by conservative procedures. We report a 35 year old lady who came with complaints of 3 months amenorrhoea and an episode of spontaneous bleeding. Urine pregnancy test was negative. Physical examination revealed a cervical polyp. Histopathological findings were consistent with villoglandular papillary adenocarcinoma associated with high grade cervical intraepithelial neoplasia (CIN-3). Left parametrial and left ureteral involvement, proved by biopsy, causing left hydroureteronephrosis was detected. The patient was thus found to be in an advanced stage, stage- III b (FIGO). The patient is currently undergoing radiotherapy. A review of literature showed that only occasional cases showing disease spread have been reported, suggesting caution in the management and regular follow up of the patient.
The diagnosis of villoglandular adenocarcinoma of cervix on cytological smears is often missed due to the relatively bland cytological features of this tumour. A 45-year-old female with an exophytic cervical growth had three cervical smears reported as unsatisfactory. A cervical biopsy followed by Wertheim's hysterectomy showed a villoglandular adenocarcinoma (VGA) of cervix. Vaginal recurrence of VGA was again missed on the first post-operative vault smear. The second and third vault smears showed characteristic features of VGA that enabled correct identification. Review of some of the smears previously reported as unsatisfactory showed architectural features of VGA in the three dimensional (3-D) fragments that were previously considered to be benign.
Cancer is increasing in incidence and the leading cause of death worldwide. Controlling and reducing cancer requires early detection and technique to accurately detect and quantify predictive biomarkers. Optical spectroscopy has shown promising non-destructive ability to display distinctive spectral characteristics between cancerous and normal tissues from different part of human organ. Nonetheless, not many information is available on spectroscopic properties of cancer cell lines. In this research, the visible-near infrared (VIS-NIR) absorbance spectroscopy measurement of cultured cervical cancer (HeLa) and prostate cancer cells (DU145) lines has been performed to develop spectral signature of cancer cells and to generate algorithm to quantify cancer cells. Spectroscopic measurement on mouse skin fibroblast (L929) was also taken for comparative purposes. In visible region, the raw cells' spectra do not produce any noticeable peak absorbance that provides information on color because the medium used for cells is colorless and transparent. NIR wavelength between 950 and 975 nm exhibit significant peak due to water absorbance by the medium. Development of spectral signature for the cells through the application of regression technique significantly enhances the diverse characteristics between L929, HeLa and DU145. The application of multiple linear regression allows high measurement accuracy of the cells with coefficient of determination above 0.94.
Cancers of the breast and cervix made up 30.4% and 12% of all cancer cases in Malaysia. Thus screening for reproductive organ cancers as women approached menopause becomes exceedingly important. The study reports the baseline assessment tests of 495 disease free urban Malaysian women aged 45 years and above who volunteered in a healthy lifestyle intervention study. The sample comprised of 58.0% premenopaused and 42.0% postmenopaused women with an average age of 51.27±5.35 years old. Over two thirds were Chinese followed by Malays and Indians. Overall, abnormal Pap smears were seen in 7.6% comprising of 1.3% cervical intraepithelial neoplasia (CIN), 6.1% human papilloma virus (HPV) infection and 0.2% atypical squmous cells of undetermined significances (ASCUS). Yeast and other infections were found in 6.9% and 1.9% respectively. Comparatively, postmenopausal women had a 2.8 fold higher cancerous changes whereas premenopausal women had a higher infection rate, 11.8% vs. 4.7% respectively (p=0.024) with comparable HPV infection rates in both. This study found 1.3% had breast cancer (BC) with 3.6% requiring a biopsy while 3.4% needed regular follow up. Postmenopaused women had more abnormal mammograms (p
The differentiation between cervical intraepithelial neoplasia 3 (CIN 3) and early squamous cell carcinoma (SCC) of the cervix may be difficult in certain situations. Identification of invasion beyond the basement membrane is the gold standard for the diagnosis of the latter. The objective of this study was to determine whether the use of Ki-67 and p53 could help in solving the above dilemma. This was a retrospective study on 61 cases of cervical neoplasms comprising of 25 cases of CIN 3 and 36 SCC. All cases were evaluated by immunohistochemistry using Ki-67 and p53 monoclonal antibodies. Results showed that the differences of Ki-67 and p53 expression between CIN 3 and SCC were statistically significant. In conclusion, Ki-67 and p53 may serve as helpful adjuncts to routinely-stained histological sections in differentiating between CIN 3 and SCC.
Microinvasive squamous cell carcinoma of the uterine cervix is a recognized entity and is defined as carcinoma with invasion of less than 5 mm penetration of the stroma and seldom metastasized. Our patient was a 70-year-old, multiparous woman who had a microinvasive, cervical, squamous cell carcinoma. The tumor had spread superficially into the entire endometrial cavity up to the fundus, totally replacing the columnar epithelium. This is an extremely rare phenomenon, with fewer than 20 cases reported so far in the literature.
Honey is reported to contain various compounds such as phenols, vitamins and antioxidants. The present study investigates the anticancer potential of Tualang honey (Agromas) (TH) in human breast (MCF-7 and MDA-MB-231) and cervical (HeLa) cancer cell lines; as well as in the normal breast epithelial cell line, MCF-10A. The cells were treated with increasing doses of TH (1-10%) for up to 72 h. Increase in lactate dehydrogenase (LDH) leakage from the cell membranes indicates that TH is cytotoxic to all three cancer cells with effective concentrations (EC(50)) of 2.4-2.8%. TH is however, not cytotoxic to the MCF-10A cells. Reactivity with annexin V fluorescence antibody and propidium iodide as analysed by flow cytometry and fluorescence microscopy shows that apoptosis occurred in these cancer cells. TH also reduced the mitochondrial membrane potential (Δψ(m)) in the cancer cell lines after 24h of treatment. The activation of caspase-3/7 and -9 was observed in all TH-treated cancer cells indicating the involvement of mitochondrial apoptotic pathway. This study shows that TH has significant anticancer activity against human breast and cervical cancer cell lines.
To date, natural products are widely used as pharmaceutical agents for many human diseases and cancers. One of the most popular natural products that have been studied for anticancer properties is thymoquinone (TQ). As a bioactive compound of Nigella sativa, TQ has shown anticancer activities through the inhibition of cell proliferation, migration, and invasion. The anticancer efficacy of TQ is being investigated in several human cancers such as pancreatic cancer, breast cancer, colon cancer, hepatic cancer, cervical cancer, and leukemia. Even though TQ induces apoptosis by regulating the expression of pro- apoptotic and anti-apoptotic genes in many cancers, the TQ effect mechanism on such cancers is not yet fully understood. Therefore, the present review has highlighted the TQ effect mechanisms on several signaling pathways and expression of tumor suppressor genes (TSG). Data from relevant published experimental articles on TQ from 2015 to June 2020 were selected by using Google Scholar and PubMed search engines. The present study investigated the effectiveness of TQ alone or in combination with other anticancer therapeutic agents, such as tyrosine kinase inhibitors on cancers, as a future anticancer therapy nominee by using nanotechnology.
Thymoquinone (TQ), the active constituent of Nigella sativa or black cumin exhibited cytotoxic effects in several cancer cell lines. In this study, the cytotoxicity of TQ in human cervical squamous carcinoma cells (SiHa) was investigated. TQ was cytotoxic towards SiHa cells with IC50 values of 10.67 ± 0.12 and 9.33 ± 0.19 μg/mL as determined by MTT assay and trypan blue dye exclusion test, respectively, after 72 h of incubation. TQ was more cytotoxic towards SiHa cells compared to cisplatin. Interestingly, TQ was less cytotoxic towards the normal cells (3T3-L1 and Vero). Cell cycle analysis performed by flowcytometer showed a significant increase in the accumulation of TQ-treated cells at sub-G1 phase, indicating induction of apoptosis by the compound. Apoptosis induction by TQ was further confirmed by Annexin V/PI and AO/PI staining. Significant elevation of p53 and down-regulation of the anti-apoptotic Bcl-2 protein was found in the treated cells, without any changes in the expression of the pro-apoptotic Bax protein. In conclusion, thymoquinone from N. sativa was more potent than cisplatin in elimination of SiHa cells via apoptosis with down-regulation of Bcl-2 protein.
This is an analysis of histologically proven neoplasms encountered in Sarawak in 1976 and 1977. There were 1447 benign and 1368 malignant tumours. The detailed breakdown of malignant neoplasms with their racial and sex distribution is reported, Lymph node involvement, with primary and metastatic lesions, constituted the largest single group with 22.3 per cent of all malignancies. The next in order of frequency was the Reproductive system with a marked preponderance of Cervical Carcinoma in females. The next in frequency were Skin cancers (8.85%) and Nasopharyngeal Carcinoma (8.4%). Primary liver cell cancer and Breast cancer constituted 5.85 per cent and 5.79 per cent respectively of all malignant tumours. The high prevalence of malignant neoplasms in Chinese is suggestive of racial predisposition.
This retrospective study is aimed at evaluating the role of CT scan in predicting parametrium involvement in early stage of cervical carcinoma. It was conducted in a Gynaecologic Oncology Centre, Hospital Alor Star from January 2004 till December 2008. All patients with operable stage I and II cervical cancer had pelvic CT scan for evaluation of parametrium involvement before undergoing radical hysterectomy and pelvic lymphadenectomy. Parametrial streakiness or presence of infiltration suggested local invasion. Following radical hysterectomy, the specimens sent for histological confirmation and the correlation between the CT scan finding and the histopathology result was studied. The result revealed a total of 104 patients with operable stage cervical carcinoma had pelvic CT scan. The sensitivity and the specificity of CT scan in assessing parametrial involvement was 33.3% and 84.8%, respectively. In conclusion, CT scan had high specificity but low sensitivity in determining parametrial involvement in early stage of cervical cancer. Hence, routine preoperative pelvic CT scan has a limited role in assessing parametrial involvement in early stage cervical carcinoma.