Latest Research News on ovarian cancer : Aug – 2020

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Latest Research News on ovarian cancer : Aug – 2020

August 8, 2020 MEDICAL Medical Science Medicine and Medical Science Medicine and Pharmacy 0

Ovarian cancer: Epidemiology, biology, and prognostic factors

Ovarian cancer varies widely in frequency among different geographic regions and ethnic groups, with a high incidence in Northern Europe and the United States, and a low incidence in Japan. The majority of cases are sporadic, and only 5% to 10% of ovarian cancers are familial. The etiology of ovarian cancer is poorly understood. Models of ovarian carcinogenesis include the theory of incessant ovulation, in which a person’s age at ovulation, i.e., lifetime number of ovulatory cycles, is an index of her ovarian cancer risk. Excessive gonadotropin and androgen stimulation of the ovary have been postulated as contributing factors. Exposure of the ovaries to pelvic contaminants and carcinogens may play a role in the pathogenesis of ovarian cancer. Epidemiologic and molecular‐genetic studies identify numerous risk and protective factors. The most significant risk factor is a family history of the disease. Recent advances in molecular genetics have found mutations in the BRCA1 and BRCA2 tumor suppressor genes responsible for the majority of hereditary ovarian cancer. Additional risk factors include nulliparity and refractory infertility. Protective factors include multiparity, oral contraceptives, and tubal ligation or hysterectomy. With five years of oral contraceptive use, women can cut their risk of ovarian cancer approximately in half; this also holds true for individuals with a family history. Stage at diagnosis, maximum residual disease following cytoreductive surgery, and performance status are the three major prognostic factors. Using a multimodality approach to treatment, including aggressive cytoreductive surgery and combination chemotherapy, five‐year survival rates are as follows: Stage I (93%), Stage II (70%), Stage III (37%), and Stage IV (25%). Semin. Surg. Oncol. 19:3–10, 2000. © 2000 Wiley‐Liss, Inc. [1]

Inhibition of Fatty Acid Synthesis Delays Disease Progression in a Xenograft Model of Ovarian Cancer

One of the key limiting factors in the treatment of advanced stage human epithelial malignancies is the lack of selective molecular targets for antineoplastic therapy. A substantial subset of human ovarian, endometrial, breast, colorectal, and prostatic cancers exhibit increased endogenous fatty acid biosynthesis and overexpress certain enzymes in the pathway. Cell lines derived from these tumors use endogenously synthesized fatty acids for cellular functions, whereas normal cells and tissues appear to utilize dietary lipids preferentially. We have previously shown that the difference in fatty acid biosynthesis between cancer and normal cells is an exploitable target for metabolic inhibitors in vitro. Here, we report observations in vivo using the i.p. model of the multiply drug-resistant OVCAR-3 human ovarian carcinoma in nude mice which demonstrate that: (a) fatty acid synthase overexpression in OVCAR-3 is comparable to levels in primary human tumors assessed by immunohistochemistry; (b) fatty acid synthetic activity of OVCAR-3 is comparably elevated in vitro and in vivo and is 4 to >20-fold higher than normal murine tissues; (c) treatment with the specific fatty acid synthase inhibitor, cerulenin, markedly reduces tumor cell fatty acid biosynthesis in vivo; (d) fatty acid synthase inhibition produces regression of established ascites tumor; and (e) treatment with cerulenin causes reduction in ascites incidence, delay in onset of ascites, and significantly increased survival (P < 0.04). [2]

Lymphadenectomy in stage I ovarian cancer

OBJECTIVE: Our experience with systematic lymphadenectomy in stage I ovarian cancer (defined as intraabdominal disease confined to the ovaries) was reviewed. We analyzed whether it would be possible to predict lymph node metastases on the basis of clinical-morphologic factors at the time of surgery. STUDY DESIGN: Forty of 100 evaluable patients operated on between 1980 and 1990 underwent comprehensive surgical staging, including total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and systemic pelvic ± paraaortic lymphadenectomy. RESULTS: Nine of the 40 (23%) patients who underwent lymphadenectomy were found to have lymph node metastases; five of these were ≤2 mm in maximum diameter. Four of the nine patients with positive nodes had ovarian tumors with a maximum diameter of only 5 cm, eight had grade 2 or 3 tumors, and eight tumors were classified as serous cystadenocarcinomas. Other clinical-morphologic factors such as ascites, adherence, or extracystic excrescences did not predict lymph node metastasis. Four of the nine patients with positive nodes survived ≥5 years with no evidence of disease. CONCLUSIONS: Lymph node metastases, some ≤2 mm in diameter, occur in an appreciable percentage of patients with intraabdominal disease confined to the ovaries. Clinical-morphologic factors at surgery cannot be relied on to predict the status of the lymph nodes. Thus we cannot recommend limiting lymphadenectomy to any specific subgroup of patients with intraabdominal disease confined to the ovaries. (AM J OBSTET GYNECOL 1994;170:656-62.) [3]

Ovarian Cancer Symptom Awareness and Its Response among Female Health Workers

Objectives: To determine the level of awareness of ovarian cancer symptoms and help-seeking responses of female health workers.

Methods: Four hundred and fifty seven female health workers were randomly selected and made to complete a structured proforma adapted from the Ovarian Cancer Awareness Measure (Ovarian CAM), which is a site-specific version of the generic Cancer Awareness Measure. Questions were asked on level of awareness of ovarian cancer early symptoms, anticipated time and the barriers to help-seeking responses.

Results: Out of 457 clients, 211 (46.2%) were able to recall at least one warning symptom of ovarian cancer while 20 (4.4%) were able to recall more than 3 warning symptoms. On the other end, when presented with a list of warning symptoms of ovarian cancer, identification ranged from 33.7-72.0% for the symptoms. As high as 28.0% could not identify any of the listed warning symptoms though some of them are also well known symptoms of late stage of ovarian cancer as well. A range of 11.7 – 27.3% of those who have ever seen a cancer patient before will seek for immediate medical help for various ovarian cancer symptoms. Also, having experienced a form of cancer before showed no relationship with the identification of all the warning signs of ovarian cancer outlined (P value ranged from .15 to .93).

Conclusion: The level of awareness of ovarian cancer warning symptomsis very low among the female health workers, and there is a poor medical help seeking habit even among those that could identify those symptoms. Efforts at improving these factors are therefore recommended. [4]

Cytotoxic and Apoptotic Effects of the Bark of Two Common Mango (Mangifera indica) Varieties from Sri Lanka on Breast and Ovarian Cancer Cells

Aims: The present study was planned to evaluate cytotoxic and apoptotic properties of the bark of two common mango varieties (Mangifera indica L.) grown in Sri Lanka [Rata Amba (RA) and Karthakolomban (KA)] in MCF-7 (ER positive breast cancer), MDA-MB-231 (triple negative breast cancer), SKOV-3 (ovarian epithelial cancer) cancer cell lines and normal mammary epithelial cells (MCF-10A).

Place and Duration of the Study: At the Institute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo between 1st of February 2015 to April 2015.

Methodology: Cancer cells and normal cells were treated with organic extracts (hexane, chloroform, ethyl acetate and methanol) of RA and KA bark and cytotoxic effects were evaluated by SRB assay. Free radical scavenging ability on 1,1-diphenyl-2-picrylhydrazyl (DPPH) was also tested for active extracts. Furthermore, apoptotic effects of cytotoxic extracts were analysed by caspase 3 and 7 activation, DNA fragmentation, acridine orange/ethidium bromide (AO/EB) and Hoechst staining.

Results: Of the four solvent extracts used, only the methanol extract showed anti-proliferative effects against all three cancer cell lines in a dose-dependent manner. Cytotoxicity of the methanol extract of RA was higher (MCF-7 IC50- 81.1 µg/mL, MDA-MB-231 IC50- 91. 5 µg/mL and SKOV-3 IC50- 71.5 µg/mL) compared to that of the methanol extract of KA (MCF-7 IC50- 123.9 µg/mL, MDA-MB-231 IC50- 111.2 µg/mL and SKOV-3 IC50- 137.2 µg/mL). Both the methanol extracts showed less cytotoxicity to normal mammary epithelial cells [IC50- 255.6 µg/mL (RA) and IC50- 615.6 µg/mL (KA)]. Methanol extracts also exhibited strong free radical scavenging ability on 1,1-diphenyl-2-picrylhydrazyl (DPPH). Furthermore, methanol extract showed apoptotic effect against all tested cancer cell lines.

Conclusion: Overall findings of this study suggest that methanol extracts of the bark of two common mango varieties tested exhibit cytotoxicity through induction of apoptosis through caspase dependent mechanisms. [5]

Reference

[1] Holschneider, C.H. and Berek, J.S., 2000, July. Ovarian cancer: epidemiology, biology, and prognostic factors. In Seminars in surgical oncology (Vol. 19, No. 1, pp. 3-10). New York: John Wiley & Sons, Inc..

[2] Pizer, E.S., Wood, F.D., Heine, H.S., Romantsev, F.E., Pasternack, G.R. and Kuhajda, F.P., 1996. Inhibition of fatty acid synthesis delays disease progression in a xenograft model of ovarian cancer. Cancer research, 56(6), pp.1189-1193.

[3] Petru, E., Lahousen, M., Tamussino, K., Pickel, H., Stranzl, H., Stettner, H. and Winter, R., 1994. Lymphadenectomy in stage I ovarian cancer. American journal of obstetrics and gynecology, 170(2), pp.656-662.

[4] Adeyemi, A. S., Afolabi, A. F. and Adedeji, O. A. (2014) “Ovarian Cancer Symptom Awareness and Its Response among Female Health Workers”, Journal of Advances in Medicine and Medical Research, 5(8), pp. 978-986. doi: 10.9734/BJMMR/2015/13354.

[5] Ediriweera, M., Tennekoon, K., Samarakoon, S., Thabrew, I. and de Silva, E. D. (2016) “Cytotoxic and Apoptotic Effects of the Bark of Two Common Mango (Mangifera indica) Varieties from Sri Lanka on Breast and Ovarian Cancer Cells”, Journal of Pharmaceutical Research International, 10(2), pp. 1-7. doi: 10.9734/BJPR/2016/24004.

 

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