Latest Research on tumour suppressor : Jan 2022

The p53 tumour suppressor gene

The cell cycle is composed of a series of steps which can be negatively or postively regulated by various factors. Chief among the negative regulators is the p53 protein. Alteration or inactivation of p53 by mutation, or by its interactions with oncogene products of DNA tumour viruses, can lead to cancer. These mutations seem to be the most common genetic change in human cancers.[1]

Cytoplasmic functions of the tumour suppressor p53

The principal tumour-suppressor protein, p53, accumulates in cells in response to DNA damage, oncogene activation and other stresses. It acts as a nuclear transcription factor that transactivates genes involved in apoptosis, cell cycle regulation and numerous other processes. An emerging area of research unravels additional activities of p53 in the cytoplasm, where it triggers apoptosis and inhibits autophagy. These previously unknown functions contribute to the mission of p53 as a tumour suppressor.[2]

The functions and regulation of the PTEN tumour suppressor

The importance of the physiological function of phosphatase and tensin homologue (PTEN) is illustrated by its frequent disruption in cancer. By suppressing the phosphoinositide 3-kinase (PI3K)–AKT–mammalian target of rapamycin (mTOR) pathway through its lipid phosphatase activity, PTEN governs a plethora of cellular processes including survival, proliferation, energy metabolism and cellular architecture. Consequently, mechanisms regulating PTEN expression and function, including transcriptional regulation, post-transcriptional regulation by non-coding RNAs, post-translational modifications and protein–protein interactions, are all altered in cancer. The repertoire of PTEN functions has recently been expanded to include phosphatase-independent activities and crucial functions within the nucleus. Our increasing knowledge of PTEN and pathologies in which its function is altered will undoubtedly inform the rational design of novel therapies.[3]

Tumour Suppressive and Organ Protective Effects of Aqueous Andrographis paniculata Leaves Extract on Benzene Induced Leukaemia Bearing Rats

Aims: To investigate and compare the protective and ameliorative role of aqueous leaf extract of Andrographis paniculata and standard drug 5-Fluorouracil on select organs of male Wistar rats exposed to benzene carcinogen.

Study Design: Histological assessment of protective and ameliorative activity of the aqueous leaf extract of Andrographis paniculata and standard drug 5-Fluorouracil in some organs of experimental animals exposed to benzene carcinogen.

Place and Duration of Study: Department of Biomedical Sciences Ladoke Akintola University of Technology, College of Health Sciences, Osogbo. Nigeria between May and August 2012.

Methodology: 72 adult male Wistar rats weighing 150-180 g were grouped into six (A-E), each group comprised of 6 rats in replicate of two (n=12).

Group A (control) received distilled water and normal saline (0.5 ml/kg each), group B received benzene chromasolv (0.2 ml at 1:10 dilution (water/2-propanol), group C received aqueous Andrographis paniculata (10 mg/kg bodyweight), group D was administered 5 -fluorouracil only (5 mg/kg body weight) for four weeks, group E was pretreated with Andrographis paniculata for 4 weeks prior to the administration of benzene chromasolv and group F was post treated with Andrographis paniculata for 4 weeks after pre-exposure to benzene chromasolv for 4 weeks. Leukaemia burden was assessed using haematological parameters such as Packed cell volume, Haemoglobin concentration, Red blood cells count and Total leukocyte count in the control and treatment groups.

Results: Results showed that leukemia was induced within 4 weeks as a significantly elevated WBC (leukocyte) counts and anaemia over the group not exposed to benzene which served as baseline were noted (p< 0.05).Organ histology showed varying lesions of the heart (mild to marked) coronary congestion, severe vacuolar degeneration and necrosis of the hepatocytes with cellular infiltration by mononuclear cells, diffuse tubular degeneration and necrosis with renal interstitial hemorrhage observed in the groups exposed to benzene carcinogen, 5-Fluorouracil and co-treatments of these two agents. However, hepato-renal and heart histio-architectures were intact in the extract pre-treatment and post-treatment groups.

Conclusion: These results suggest that Andrographis paniculata might be more effective than some other drugs currently in use as cancer suppressive chemotherapeutic agents and also may be a novel bioagent for the treatment of acute or chronic injuries induced on the liver, kidneys and heart by toxicants and carcinogens.[4]

Recurrent Eccrine Porocarcinoma: A Case Report

Eccrine porocarcinoma is a very rarely seen malignant skin tumour which originates from the intra-epithelial section of the eccrine sweat glands. They are generally seen in the elderly and are most often located in the lower extremities. This tumour which has a poor prognosis and displays different biological behaviour, often has a tendency to recurrence and metastasis is seen in the skin and lymph nodes. The basis of treatment is surgical excision and if there is lymph node involvement, regional lymph node dissection must be  applied. The case is here presented of  a 67-year old patient with eccrine porocarcinoma which developed in the inguinal region and showed recurrence.[5]

[1] Levine, A.J., Momand, J. and Finlay, C.A., 1991. The p53 tumour suppressor gene. Nature, 351(6326), pp.453-456.

[2] Green, D.R. and Kroemer, G., 2009. Cytoplasmic functions of the tumour suppressor p53. Nature, 458(7242), pp.1127-1130.

[3] Song, M.S., Salmena, L. and Pandolfi, P.P., 2012. The functions and regulation of the PTEN tumour suppressor. Nature reviews Molecular cell biology, 13(5), pp.283-296.

[4] Olufemi, A.E., Folarin, O.R. and Igbeneghu, C., 2014. Tumour suppressive and organ protective effects of aqueous andrographis paniculata leaves extract on benzene induced leukaemia bearing rats. Annual Research & Review in Biology, pp.1070-1079.

[5] Karaköse, O., Pülat, H., Eken, H., Zihni, İ., Özçelik, K.Ç., Bozkurt, K.K. and Eroğlu, H.E., 2016. Recurrent Eccrine Porocarcinoma: A Case Report. Journal of Advances in Medicine and Medical Research, pp.1-5.

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