Screening of BRCA1/2 Mutations Using Direct Sequencing in Indonesian Familial Breast Cancer Cases

Anwar, Sumadi Lukman,Haryono, Samuel J,Aryandono, Teguh,Datasena, I Gusti Bagus Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.4

Breast cancer has emerged as the most prevalent cancer among women worldwide, including in Indonesia. The contribution of genes associated with high-risk breast-ovarian cancers, BRCA1 and BRCA2, in the Indonesian population is relatively unknown. We have characterized family history of patients with moderate- to high-risk of breast cancer predisposition in 26 unrelated cases from Indonesia for BRCA1/2 mutation analyses using direct sequencing. Known deleterious mutations were not found in either BRCA1 or BRCA2 genes. Seven variants in BRCA2 were documented in 10 of 26 patients (38%). All variants were categorized as unclassified (VUSs). Two synonymous variants, c.3623A>G and c.4035T>C, were found in 5 patients. One variant, c4600T>C, was found in a 38 year old woman with a family history of breast cancer. We have found 4 novel variants in BRCA2 gene including c.6718C>G, c.3281A>G, c.10176C>G, and c4490T>C in 4 unrelated patients, all of them having a positive family history of breast cancer. In accordance to other studies in Asian population, our study showed more frequent variants in BRCA2 compared to BRCA1. Further studies involving larger numbers of hereditary breast cancer patients are required to reveal contribution of BRCA1/2 mutations and/or other predisposing genes among familial breast cancer patients in Indonesia.

Caveolin-1 in Breast Cancer: Single Molecule Regulation of Multiple Key Signaling Pathways

Anwar, Sumadi Lukman,Wahyono, Artanto,Aryandono, Teguh,Haryono, Samuel J Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.16

Caveolin-1 is a 22-kD trans-membrane protein enriched in particular plasma membrane invaginations known as caveolae. Cav-1 expression is often dysregulated in human breast cancers, being commonly upregulated in cancer cells and downregulated in stromal cells. As an intracellular scaffolding protein, Cav-1, is involved in several vital biological regulations including endocytosis, transcytosis, vesicular transport, and signaling pathways. Several pathways are modulated by Cav-1 including estrogen receptor, EGFR, Her2/neu, $TGF{\beta}$, and mTOR and represent as major drivers in mammary carcinogenesis. Expression and role of Cav-1 in breast carcinogenesis is highly variable depending on the stage of tumor development as well as context of the cell. However, recent data have shown that downregulation of Cav-1 expression in stromal breast tumors is associated with frequent relapse, resistance to therapy, and poor outcome. Modification of Cav-1 expression for translational cancer therapy is particularly challenging since numerous signaling pathways might be affected. This review focuses on present understanding of Cav-1 in breast carcinogenesis and its potential role as a new biomarker for predicting therapeutic response and prognosis as well as new target for therapeutic manipulation.

Nutrient Requirements of Exercising Swamp Buffalo, Bubalus bubalis, from Materials Balance and In Vivo Body Composition by the Body Density Method. I. Aspects of Energy and Protein Metabolism in Working Cows

Mahardika, IG.,Sastradipradja, D.,Sutardi, T.,Sumadi, IK. Asian Australasian Association of Animal Productio 2000 Animal Bioscience Vol.13 No.5

Four young swamp buffalo cows of similar age ranging in weight between 280 to 380 kg and trained to do physical work were used in a study to determine energy and protein requirements for draught using a $4{\times}4$ Latin square designed experiment. The experiment consisted of field trials employing 4 levels of work load, e.g. no work as control, and loads amounting 450 to 500 Newton (N) pulled continuously for 1, 2 and 3 h daily for 14 consecutive days. Cows were fed king grass (Penisetum purpuroides) ad libitum and were subjected to materials balance trials. Body composition was estimated in vivo by the body density method and daily energy expenditure (EE) was calculated from ME minus retained energy (RE). The results show that EE while not working ($EE_{resting}$) was $0.42kgW^{0.75}MJ/d$ and maintenance ME ($ME_m$) was $0.37kgW^{0.75}MJ/d$. ME requirement increased to 1.65 times maintenance for the work of 3 hours. The energy expended for doing exercise ($E_{exercise}$) was 9.56, 20.0 and 25.86 MJ/cow for treatments 1, 2 and 3 II, respectively. Fat retention was absent in all groups of working cows, but protein retention was only negative for cows undertaking 3 h work. The relationship between $E_{exercise}$ (MJ), work load (F, kN), work duration (t, h) and body mass (W, kg) was found to be: $E_{exercise}=(0.003F^{1.43}t^{0.93})/W^{0.09}MJ$. The maintenance requirement for digestible protein was $2.51kgW^{0.75}g/d$, whereas digestible protein for growth ($DP_{growth}$) and for work ($DP_{work}$) followed the equations: $DP_{growth}=[(258+1.25W^{0.75}){\Delta}Wkg/d]g$ and $DP_{work}=[12.59e^{0.95t}]g$, respectively The coefficients a, b and c for the calculation of $E_{exercise}$ components according to the Lawrence equation were found to be 2.56 J/kgW.m, 5.2 J/kg load carried.m and 0.29, respectively, thus efficiencies to convert ME into work were 0, 16.09, 27.3 and 32.44% for control, 1, 2 and 3 h/d work, respectively. ME and DP requirements for a 250 to 400 kg working buffalo cow allowing to growth up to 0.5 kg/d are presented.

Nutrient Requirements of Exercising Swamp Buffalo, Bubalus bubalis. II. Details of Work Energy of Cows and Its Relation to Heart Rate

Mahardika, I.G.,Sastradipradja, D.,Sutardi, T.,Sumadi, I.K. Asian Australasian Association of Animal Productio 2000 Animal Bioscience Vol.13 No.7

Four young swamp buffalo cows of similar age ranging in body weight (W) between 280 to 380 kg and trained for doing physical exercise were used in two consecutive experiments, each using a latin square design, to determine energy expenditure for draught. The experiments consisted of field trials using 4 levels of work load, i.e. no work as control and loads amounting 450 to 500 Newton (N) continuous traction for respectively 1, 2 and 3 h daily for 14 consecutive days for experiment 1, and no work, traction loads equaling 5, 10 and 15% of W for 3 h daily for 14 days for experiment 2. Heart rate during rest and exercise was monitored using PE-3000 HR monitor. Cows were fed only king grass (Penisetum purpuroides) ad libitum and were subjected to balance trials. Body composition was estimated in vivo by the body density method and daily energy expenditure (EE) was calculated from ME minus RE. RE was calculated from the changes in body-protein and -fat measured before and immediately after the 14 d experimental period assuming an energy equivalent of 39.32 MJ/kg fat and 20.07 MJ/kg protein. $E_{exercise}$ ($EE_{work}\;-\;EE_{resting}$), which was the energy spent for doing the traction during 1, 2 and 3 h was 7.13, 15.45 and 19.90 MJ, respectively. $EE_{work}$ for the 1 h treatment group was 39.75 MJ/d equivalent to 1.30 times $EE_{resting}$. The values for the 2 and 3 h treatment groups were 1.75 and 1.86 times resting energy requirement, respectively. Absolute efficiency of work in all exercise trials of experiment 2 was around 27.28%. The increases of daily $E_{exercise}$ values were correlated to elevation of heart rate (HR) according to the equation $E_{exercise}=(0.270HR^{0.363}\;-\;1)$ MJ, while draught force related to heart rate according to the equation DF (N)=6.66 HR - 361.62. Blood glucose and triglyceride levels were gradually elevated with time during the course of exercise. Mean values of blood glucose were 91.7, 115.0 and 116.2 mg/dl for cows after 1, 2 and 3 h pulling loads at 15% W respectively as compared to 88.2 mg/dl prior to work. In the same order and treatment, mean blood triglyceride concentrations were 13.5, 13.3 and 14.8 mg/dl, and 11.5 mg/dl for control. For blood lactate, the values were 1.68, 1.63 and 1.66 mM, and 0.80 mM for control. Glucose was used as the major source of energy during the initial phase of exercise, but for prolonged work, fat will replace carbohydrate as the main substrate. Accumulation of lactate persisted for some time at the end of the exercise trials.

Low Hand Grip Strength, Mid-Upper Arm Muscle Area, Calf Circumference, Serum Albumin Level, and Muscle Fiber Diameter as Risk Factors for Independent Walking Inability in Patients with Hip Fracture 6 Weeks after Bipolar Hemiarthroplasty Surgery

Sherly Desnita Savio,I Ketut Siki Kawiyana,I Gede Eka Wiratnaya,I Wayan Juli Sumadi,I Ketut Suyasa 대한정형외과학회 2024 Clinics in Orthopedic Surgery Vol.16 No.2

Background: Bipolar hemiarthroplasty, one of the main treatment modalities for hip fracture, does not always promise the ability to walk independently after surgery. Patients with the same fracture characteristics and comorbidities, implants, and operators may also have different outcomes. Sarcopenia is thought to be one of the causes of the inability to walk independently after this operation; however, it has not been widely studied and is often overlooked. Methods: This study used a case-control design with 23 patients in the case group (patients unable to walk independently) and 23 patients in the control group (patients able to walk independently). Sampling was carried out consecutively according to the inclusion and exclusion criteria based on the medical records of patients with hip fractures after bipolar hemiarthroplasty at our hospital. In the preoperative period, hand grip strength (HGS), mid-upper arm muscle area (MUAMA), calf circumference (CC), serum albumin level, and total lymphocyte count were measured. A muscle biopsy was performed intraoperatively from the gluteus muscle with the amount of 200–350 mg. The patient’s walking ability was assessed in the polyclinic using the Timed Up and Go test 6 weeks postoperatively. The statistical tests used were descriptive statistics, proportion comparison analysis with the chisquare test, and multiple logistic regression test. Results: Univariate analysis using chi-square test proved HGS, MUAMA, CC, serum albumin level, and muscle fiber diameter as risk factors for inability to walk independently 6 weeks after bipolar hemiarthroplasty (p = 0.003, p = 0.003, p = 0.006, p = 0.044, and p = 0.000, respectively). Logistic regression test proved 3 direct risk factors for the inability to walk independently 6 weeks after bipolar hemiarthroplasty, namely MUAMA, serum albumin level, and muscle fiber diameter, as the strongest predictive factor (adjusted odds ratio, 63.12). Conclusions: Low MUAMA, serum albumin levels, and muscle fiber diameter are direct risk factors for the inability to walk independently in hip fracture patients 6 weeks after bipolar hemiarthroplasty.