Comparative Study of Hypo-Fractionated Radiotherapy Versus Conventional Radiotherapy in Breast Cancer.

BACKGROUND: Breast cancer is the most commonly diagnosed cancer causing death among females worldwide. Radiotherapy after lumpectomy/mastectomy in breast cancer cases is a successful treatment modality taking five weeks to complete. The aim of the present study is to compare the effectiveness of hypo-fractionated radiotherapy in breast cancer patients with conventional radiotherapy with respect to outcome and toxicity. METHODS: Sixty patients were randomly divided equally into a conventional group, Group A (dose: 50 Gy in 25 fractions), and a hypo-fractionated short-course radiotherapy group, Group B (dose: 40 Gy in 16 fractions). After thorough clinical and laboratory examination of all patients, the disease status was assessed prior to radiotherapy and three and six months after completion of radiotherapy. The cardiopulmonary function was assessed using echocardiography and pulmonary function tests prior to the procedure. The assessment of the development of toxicity (dysphagia, skin, lung, and lymphedema) was done during every clinical visit. RESULTS: The mean age of patients was 53.28 ± 9.73 years in Group A, and 55.67 ± 10.41 years in Group B (p=0.82). The right breast was involved in 13 (43.4%) patients in Group A and 14 (46.6%) in Group B, and the left breast was involved n 17 (56.6%) patients in Group A and 16 (53.4%) in Group B (p=0.81). Most of the patients were post-menopausal; 24 (80%) in Group A and 25 (83.4%) in Group B (p=0.91). Eleven (36.6%) patients were of stage T2N1M0 in both groups. However, no statistical difference was observed between the groups in the TNM (tumor, node, and metastasis) staging using the AJCC (American Joint Committee on Cancer) criteria (p=0.26). On comparing the responses in Group A and Group B, no significant difference was observed in either of the groups from immediate post-treatment to the 12-month follow-up period (p=0.53 and p=0.64, respectively). CONCLUSION: Hypo-fractionated radiotherapy is as effective as conventional radiotherapy and can be used as an alternative method for treatment following breast cancer surgery.

A Comparative Study on Clinical Evaluation of the Hypolipidemic Effects of Allium sativum, Trigonella foenum-graecum, Commiphora mukul, Picrorhiza kurroa, and Piper nigrum: A Pilot Study.

Background Cardiovascular disease is a leading cause of morbidity and mortality. Therefore, it is essential to prevent cardiovascular diseases by correcting modifiable risk factors such as lowering lipid levels, lowering blood pressure, improving eating habits, giving up smoking, etc. The present study assessed the efficacy of herbal preparation containing Allium sativum (A. sativum), Commiphora mukul (C. mukul), and Trigonella foenum-graecum (T. foenum-graecum) in patients with hyperlipidemia. Methodology Patients were given extracts of A. sativum 350 mg, T. foenum-graecum 350 mg, C. mukul 200 mg, Picrorhiza kurroa (P. kurroa) 200 mg, and Piper nigrum (P. nigrum) 5 mg. Unichem Laboratories, Mumbai, provided placebo tablets similar in shape and size to herbal tablets. Patients were assessed for compliance, and a complete lipid profile was done at DO, D15, D46, D76, and D106. In addition, total cholesterol and high-density lipoprotein-cholesterol (HDL-C) serum triglyceride were estimated by the respective methods throughout the study. Results The weight of the patients remained stable, the mean weight before being 65.42 ± 8.35 kg and after completion of the study being 65.42 ± 8.35 kg. There were no changes in the ECG during or after the drug therapy in any of the patients. Group A comprised nine patients, and group B had ten patients. Serum creatinine (mg %) was 0.94 and 0.95, fasting blood sugar mg (%) was 111.05 and 99.63, and postprandial blood sugar (mg %) was 150.89 and 147.94 on pre-treatment and post-treatment, respectively. The mean serum triglyceride levels in group A were 271.11, 261.11, 293.89, 167.22, and 128.89, and serum HDL- C levels were 46.11, 46.11, 54.44, 52.22, and 54.44. Serum triglyceride levels in group B were 268, 268.5, 202, 171, and 116, and serum HDL- C levels were 48.5, 48, 50, 50, and 53.5 on day 0, 15, 46, 76, and 106, respectively. A significant reduction in total cholesterol levels was observed on D46, D76, and D106, with a maximum reduction on D76 (25.36%). Similarly, a reduction in serum triglyceride was also observed on D46, D76, and D106, with a maximum reduction on D106 (52.02%). A significant difference was observed (P <0.05). There was also a significant reduction of low-density lipoprotein cholesterol (LDL-C) on D46, D76, and D106, with the maximum reduction on D76 (28.79%). There was a significant rise of HDL-C on D46 and D106, with a maximum rise on D106 (15.41%). A significant difference was observed (P <0.05). Conclusion The study drugs are safe and efficacious in reducing the total cholesterol, serum triglycerides, LDL-C levels, and increasing HDL-C levels.

Epstein-Barr virus infection mediated TP53 and Bcl-2 expression in nasopharyngeal carcinoma pathogenesis.

Epstein Barr virus (EBV) stimulates neoplastic transformation of nasopharyngeal epithelial cells through various molecular mechanisms, predominantly affecting inactivation of tumor-suppressor genes and activation of oncogenes. EBV infection is a major risk factor for nasopharyngeal carcinoma (NPC), yet its role in the carcinogenesis is not clear. EBV infection alters the expression of antiapoptotic proteins and tumor suppressor proteins. Therefore, this study investigated the correlation between EBV infection status with B cell lymphoma-2 (Bcl-2) and TP53 protein expression amongst laryngeal and nasopharyngeal cancer cases. This study was performed using 22 nasopharyngeal and 11 laryngeal cancer cases. EBV infection status, TP53 and Bcl-2 protein expression was studied using immunohistochemistry. The majority of the laryngeal cancer cases exhibited a poor prognosis and presented low Bcl-2 expression. A total of 22.7% cases were infected with EBV in the NPC cases. Upregulated TP53 expression was associated with EBV infection in the NPC cohort, and EBV infection was correlated with TP53 upregulation in the patients with NPC, suggesting mutual regulation between TP53 and EBV.

Exome sequencing of Saudi Arabian patients with ADPKD.

Purpose: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive development of kidney cysts and enlargement and dysfunction of the kidneys. The Consortium of Radiologic Imaging Studies of the Polycystic Kidney Disease (CRISP) cohort revealed that 89.1% had either a PKD1 or PKD2 mutation. Of the CRISP patients with a genetic cause detected, mutations in PKD1 accounted for 85%, while mutations in the PKD2 accounted for the remaining 15%. Here, we report exome sequencing of 16 Saudi patients diagnosed with ADPKD and 16 ethnically matched controls. Methods: Exome sequencing was performed using combinatorial probe-anchor synthesis and improved DNA Nanoballs technology on BGISEQ-500 sequencers (BGI, China) using the BGI Exome V4 (59 Mb) Kit. Identified variants were validated with Sanger sequencing. Results: With the exception of GC-rich exon 1, we obtained excellent coverage of PKD1 (mean read depth = 88) including both duplicated and non-duplicated regions. Of nine patients with typical ADPKD presentations (bilateral symmetrical kidney involvement, positive family history, concordant imaging, and kidney function), four had protein truncating PKD1 mutations, one had a PKD1 missense mutation, and one had a PKD2 mutation. These variants have not been previously observed in the Saudi population. In seven clinically diagnosed ADPKD cases but with atypical features, no PKD1 or PKD2 mutations were identified, but rare predicted pathogenic heterozygous variants were found in cystogenic candidate genes including PKHD1, PKD1L3, EGF, CFTR, and TSC2. Conclusions: Mutations in PKD1 and PKD2 are the most common cause of ADPKD in Saudi patients with typical ADPKD. Abbreviations: ADPKD: Autosomal dominant polycystic kidney disease; CFTR: Cystic fibrosis transmembrane conductance regulator; EGF: Epidermal growth factor; MCIC: Mayo Clinic Imaging Classification; PKD: Polycystic kidney disease; TSC2: Tuberous sclerosis complex 2.

Helical and kinase domain mutations of PIK3CA, and their association with hormone receptor expression in breast cancer.

Breast cancer is one of the major causes of female morbidity and mortality, accounting for ~25% of the total cancer cases in women. Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic α subunit (PIK3CA) mutations serve a major role in downstream signaling of receptor tyrosine kinases. The present study aimed to elucidate the frequency of exon 9 and 20 mutations of PIK3CA and their role in disease progression. A total of 118 tumor samples from confirmed breast cancer patients were collected from the histopathology laboratory at King Fahd Hospital of the University (Al-Khobar, Saudi Arabia). Sanger sequencing was performed on extracted DNA to identify the mutations on exons 9 and 20 of PIK3CA. The results were further validated by competitive allele-specific TaqMan polymerase chain reaction. Three mutations, namely E542K and E545K within exon 9, and H1047R within exon 20, were observed in 25 patients (21.2%). Among these, 18 patients carried the H1047R mutation of the kinase domain, while the remaining 7 patients carried mutations in the helical domain. PIK3CA mutations were associated with the estrogen receptor-positive/progesterone receptor-positive (ER+/PR+) group of tumors in contrast to the ER-/PR- group (P=0.021). Furthermore, it was observed that the PIK3CA mutation was associated with a poor disease prognosis. Taken together, the current study emphasized the potential of PIK3CA mutations as an important biomarker for breast cancer classification and the possible use of PIK3CA inhibitor as targeted therapy for breast cancer.