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Journal of Cancer Research Updates

Obesity and Breast Cancer: Molecular and Epidemiological Evidence
Pages 30-42
Nehad M. Ayoub and Amal Kaddoumi

DOI: http://dx.doi.org/10.6000/1929-2279.2015.04.01.3

Published: 19 February 2015

 


Abstract: Carcinoma of the breast is a leading cause of cancer deaths among women world-wide. Obesity is recognized as a well-established risk factor for epithelial tumors including the mammary epithelium. Adipose tissue is considered to be metabolically active organ with the ability to secrete a wide range of biologically active adipokines. Multiple studies have evaluated the potential mechanisms correlating obesity to increased risk of breast cancer. Altered circulating levels of adipokines or changed adipokine signaling pathways are now increasingly recognized to be associated with breast cancer development and progression. Leptin and adiponectin were the main adipokines that have been investigated in the context of breast cancer in both preclinical and epidemiological studies. Obesity is also believed to promote inflammatory response and induce activity of key enzymes like aromatase, leading to higher risk of breast cancer development. The goal of this review is to provide recent insights into the potential molecular mechanisms linking adipokines to the etiopathogenesis of breast cancer including recently identified adipokines and trying to correlate these molecular mechanisms to more established metabolic and hormonal dysregulations of obesity. A better understanding of the interplay between adipokines and other deregulated mechanisms in obesity is important for the development of preventive strategies with therapeutic potential against breast cancer in obese patients.

Keywords: Adipokines, Obesity, Leptin, Adiponectin, Visfatin, Inflammation.
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Journal of Cancer Research Updates

Perioperative Management in a Child with Familial Bilateral Pheochromocytoma
Pages 43-46
Saurabh Joshi, Chetan Saraya, Shri Prakash Singh, Jasbir Singh Khanuja and Umesh Kumar Valecha

DOI: http://dx.doi.org/10.6000/1929-2279.2015.04.01.4

Published: 19 February 2015

 


Abstract: Purpose: Diagnosis and perioperative management of bilateral adrenal pheochromocytoma with a successful outcome is an apt combination of clinical knowledge and anaesthetic skills. Detailed history, meticulous physical examination, relevant laboratory investigations along with good preoperative pharmacological optimization and fluid resuscitation plays an important role in the perioperative period. Genetic testing and counseling should be offered to all the family members of patients suspected of familial predisposition. We report the anesthetic management of 10 year old male child with bilateral adrenal pheochromocytoma with family history of disease.

Clinical Features: A10-year old male, presented to our pediatric outpatient clinic with gradually increasing holocranial headache, blurring of vision, sweating, photophobia, progressive quietness in nature and poor performance in school, increased thirst and urine output for one week along with pain over bilateral lower limbs and difficulty walking without support for 20days. Parents also reported two episodes of generalized convulsions with one episode of opisthotonic posturing and up rolling of eyes, which was sustained for 50 min. Family history of three sudden deaths, and father, a known case of pheochromocytoma along with clinical presentation, raised the suspicion of familial pheochromocytoma.

Conclusion: Though pheochromocytomas are rare tumours, a high level of suspicion in paediatric age group, where patients don’t present with classical symptoms, leads to early diagnosis and management and prevents catastrophic events. Young patients with bilateral disease and positive family history should be offered genetic testing. Preoperative catecholamine blockade and meticulous anaesthetic and surgical management are the keys to successful perioperative management of bilateral pheochromocytoma.

Keywords: Pheochromocytoma, Familial, Bilateral, Anesthetic management.
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Journal of Cancer Research Updates

Carnitine Deficiency: A Causative Clue or a Sequel in Carboplatin Myelosuppression
Pages 226-235
Hossam M.M. Arafa, Raed S. Ismail, Nesreen Nabil and Adel M. Mostafa

DOI: http://dx.doi.org/10.6000/1929-2279.2014.03.04.7

Published: 04 December 2014

 


Abstract: We have previously demonstrated that carnitine deficiency aggravated paracetamol-induced hepatopathy and carboplatin-induced nephropathy. As a continuum, we have addressed in the current study as to whether carboplatin-induced myelosuppression would be exacerbated by carnitine deficiency. Challenging male Wistar rats with a single dose of carboplatin (35 mg/kg, IP) induced bone marrow suppression manifested as anemia, leucopenia, thrombocytopenia as well as increased frequencies of the micronucleated bone marrow cells; MPCE and MNCE with notable reduction in the P/N ratio. The platinum drug also elevated serum TNF-a and reduced serum free and total carnitine levels. Besides, ATP levels in red and T cells were lowered. Likewise, the mitochondrial membrane potential in T lymphocytes was reduced following the use of the potentiometric dye; JC-1, and this was well correlated with cellular ATP production. Carnitine deficiency exacerbated carboplatin myelotoxicity as it exaggerated all biochemical, hematological and cytogenetic parameters. To address as to whether carnitine deficiency was a causative clue or merely a sequel of carboplatin myelotoxicity, L-carnitine was supplemented ahead of carboplatin challenege. Herein, L-carnitine mitigated all the biochemical, hematological and cytogenetic effects possibly via modulating the release of TNF-a, cellular ATP production and restoring the mitochondrial membrane potential. Irrespective of the mechanisms involved, the current results may afford the potential role for carnitine supplementation as add-on nutraceutical in carboplatin-based chemotherapy.

Keywords: Carboplatin, Carnitine, Myelosuppression, Micronucleus Assay, TNF-α, ATP Mitochondrial membrane potential.
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Journal of Cancer Research Updates

The Polymorphism of EME1 Gene is Associated with an Increased Risk of Lung Cancer: A Case-Control Study from Chinese Population
Pages 174-181
Jianwei Zhao, Yongxiu Chen, Xiaoxiao Lu, Di Wu, Jiansong Chen, Zhihuang Chen, Lin Liu, Lei Yang, Lan Zhang, Yifeng Zhou and Jiachun Lu

DOI: http://dx.doi.org/10.6000/1929-2279.2014.03.04.1


Published: 24 November 2014


Abstract: DNA double-strand breaks (DSBs) can lead to genomic instability and cancer susceptibility if unrepaired. EME1 is one of the key proteins that participate in the recognition and repair of DSBs in humans. We hypothesized that the exonic variants of EME1 are associated with lung cancer risk. In a two-stage case-control study of 1559 lung cancer patients and 1679 cancer-free controls, we genotyped two exonic variants of EME1(Glu69Asp: rs3760413T>G and Ile350Thr: rs12450550T>C) and analyzed their associations with risk of lung cancer. We found that the Asp variant genotypes conferred 1.35-folds risk of lung cancer compared to the Glu/Glu genotype (OR = 1.35, 95%CI = 1.18-1.56, P = 2.18 × 10-5) in both stages. However, the SNP Ile350Thr was not confirmed to be associated with cancer risk in both stages. Moreover, by querying the gene expression database, we further found that the 69Asp variant genotypes confer a significantly lower mRNA expression of EME1 than the Glu/Glu genotype in 260 cases of lymphoblastoid cells (P=0.013). Our findings suggested that the SNP Glu69Asp of EME1 is associated with an increased risk of lung cancer, and may be a functional biomarker to predict lung cancer risk in Chinese. Validations in other ethnics are warranted.

Keywords: Lung cancer, EME1, exonic variant, functional biomarker.
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