Cooperation between BRCA1 and vitamin D is critical for histone acetylation of the p21waf1 promoter and growth inhibition of breast cancer cells and cancer stem-like cells.

Carriers of germline mutations in the BRCA1 gene have a significant increased lifetime risk for being diagnosed with breast cancer. The incomplete penetrance of BRCA1 suggests that environmental and/or genetic factors modify the risk and incidence among mutation carriers. Nutrition and particular micronutrients play a central role in modifying the phenotypic expression of a given genotype by regulating chromatin structure and gene expression.

Adoptive cell therapy with autologous tumor-infiltrating lymphocytes and high-dose interleukin-2 for metastatic melanoma: The surgeon's perspective.

Tumor-infiltrating lymphocytes (TILs) are produced by resecting tumor tissue and growing and expanding ex vivo large quantities of autologous T cells. Once the TILs are ready for infusion, the patient undergoes a non-myeloablative lympho-depleting course of chemotherapy and subsequent TIL infusion with high-dose bolus IL-2. This study reviews the surgical experience of the TIL program at the Chaim Sheba Cancer Research Center in Israel.

BRCA1-dependent Chk1 phosphorylation triggers partial chromatin disassociation of phosphorylated Chk1 and facilitates S-phase cell cycle arrest.

Chk1 phosphorylation by the PI3-like kinases ATR and ATM is critical for its activation and its role in prevention of premature mitotic entry in response to DNA damage or stalled replication. The breast and ovarian tumor suppressor, BRCA1, is among several checkpoint mediators that are required for Chk1 activation by ATM and ATR. Previously we showed that BRCA1 is necessary for Chk1 phosphorylation and activation following ionizing radiation.

Appendiceal carcinoid at a large tertiary center: pathologic findings and long-term follow-up evaluation.

Background: Appendiceal carcinoid tumor is the most common type of primary appendiceal malignant lesion. Nonetheless; it is an exceedingly rare diagnosis; found in only about .3% to .

Laparoscopic sleeve gastrectomy as a revisional option after gastric band failure.

Background: Laparoscopic adjustable gastric banding (LAGB) is an effective bariatric procedure with low morbidity and mortality. Unfortunately, it is fraught with high failure rates in long-term follow-up. Laparoscopic sleeve gastrectomy (LSG) is an emerging procedure, quickly gaining momentum in the arsenal of bariatric practice as a first step toward gastric bypass/biliopancreatic diversion or as a stand-alone operation.

Pre-operative cardiac workup after anthracycline-based neoadjuvant chemotherapy. Is it really necessary?

Introduction: In patients receiving pre-operative anthracyclines for locally advanced breast cancer, early cardiotoxicity is a well-recognised complication that may interfere with surgery. The aim of this study was to assess the safety of breast surgery after neoadjuvant treatment with Doxorubicin.

Patients And Methods: A retrospective study of breast cancer patients treated with Doxorubicin as part of their neoadjuvant protocol.

Association between very young age and adverse characteristics of breast cancer at presentation amongst Israeli women.

Background: Up to 4% of breast cancer cases occur in women younger than 35 years. Studies have suggested an association between breast cancer at a young age, poorer outcome, and adverse clinical and pathologic characteristics. It is unclear whether age is an independent prognostic factor.

Single-nucleotide polymorphisms in the p53 pathway genes modify cancer risk in BRCA1 and BRCA2 carriers of Jewish-Ashkenazi descent.

Germline mutations in the BRCA1 and BRCA2 genes are associated with a significantly increased lifetime risk for developing breast and/or ovarian cancer. However, incomplete penetrance and substantial variability in age of disease onset among carriers of the same mutation suggests the involvement of additional modifier genes and/or environmental factors. Somatic inactivating mutations in the p53 gene and genes of the p53 pathway often accompany BRCA1/2-associated tumors.

The significance of occult carcinoids in the era of laparoscopic appendectomies.

Background: We present data acquired in our institution about the incidence of incidental appendiceal carcinoids over a period of 16 years. The possibility of occult carcinoids raises the question of appendectomy of a noninflamed appendix during diagnostic laparoscopy for suspected appendicitis.

Methods: We performed a retrospective chart analysis of the surgical registry of a university-affiliated tertiary care center of a major population area for the past 16 years.

Outcome of thick (> 4 mm) node-negative melanomas.

Background: Patients with thick melanomas > 4 mm deep are at great risk for regional and distant metastatic disease. Historically, the appropriate management of thick melanomas has remained unclear and there is no consensus in the literature. Many have taken the nihilistic view that surgical intervention to excise regional nodal basins is not justified in light of the poor overall prognosis and risk of occult distant disease.

The posterior intrahepatic approach to the left portal pedicle using the ligamentum venosum: anatomical basis.

Purpose: Prevention of blood loss in liver resections is essential for reducing postoperative morbidity. The main method to control bleeding during surgery of the left hemiliver is occlusion of the left portal pedicle. This may be accomplished by hilar, fissural or posterior intrahepatic techniques.

Timing of sentinel lymph node biopsy in patients receiving neoadjuvant chemotherapy for breast cancer.

Objective: To address optimal timing of sentinel lymph node biopsy (SLNB) in breast cancer patients undergoing neoadjuvant treatment.

Methods: The study population included 117 patients with locally advanced cancer with clinically negative nodes treated with primary chemotherapy. Group 1 underwent SLNB and completion axillary lymph node dissection (ALND) in conjunction with lumpectomy/mastectomy, after neoadjuvant treatment (n = 31).

High efficacy of pre-operative trastuzumab combined with paclitaxel following doxorubicin & cyclophosphamide in operable breast cancer.

Background: Trastuzumab in combination with adjuvant chemotherapy improves disease free survival and overall survival in HER2 over-expressing breast cancer patients. Data concerning the use of trastuzumab in the neo-adjuvant setting is limited. We aimed to compare outcome of HER2 over-expressing breast cancer patients treated with either standard chemotherapy, consisting of doxorubicin, cyclophosphamide and a taxane to outcome of patients treated with the same chemotherapy regimen with the addition of trastuzumab in concurrence with paclitaxel.

Germline CHEK2 mutations in Jewish Ashkenazi women at high risk for breast cancer.

Background: Germline mutations in BRCA1 and BRCA2 genes account for only 20-40% of familial breast cancer cases. The CHEK2 gene encodes a checkpoint kinase, involved in response to DNA damage, and hence is a candidate gene for breast cancer susceptibility. Indeed, the CHEK2*1100delC truncating mutation was reported in a subset of mostly North European breast cancer families.

MDM2 SNP309 accelerates breast and ovarian carcinogenesis in BRCA1 and BRCA2 carriers of Jewish-Ashkenazi descent.

A functional single nucleotide polymorphism in the promoter of the MDM2 gene, SNP309 (T>G), was recently found to accelerate tumorigenesis in early onset cancer cases. The SNP309 G-allele, introduces an SP1 site in the MDM2 promoter, resulting in enhanced MDM2 expression and activity. Thus, the G-allele of MDM2 SNP309 may represent a cancer predisposing allele.

Elevated insulin-like growth factor-I receptor (IGF-IR) levels in primary breast tumors associated with BRCA1 mutations.

The insulin-like growth factors (IGFs) play a pivotal role in breast cancer. Inherited predisposition to breast and ovarian cancer is associated with germline BRCA1/BRCA2 mutations. To evaluate the impact of BRCA1 mutations on IGF-IR gene expression, we performed an immunohistochemical analysis of IGF-IR in primary breast tumors from BRCA1 mutation carriers and non-carriers.

Estrogen receptor regulates insulin-like growth factor-I receptor gene expression in breast tumor cells: involvement of transcription factor Sp1.

The insulin-like growth factors, IGF-I and IGF-II are a family of mitogenic polypeptides with important roles in growth and differentiation. The biological actions of the IGFs are mediated by the IGF-I receptor (IGF-IR), a cell-surface tyrosine kinase, whose activation by serum IGF-I seems to be a key step in breast cancer initiation. Evidence accumulated indicates that estrogens stimulate the expression and activity of IGF axis components.

BRCA1 at the crossroad of multiple cellular pathways: approaches for therapeutic interventions.

Approximately 10% of the cases of breast cancer and invasive ovarian cancer are hereditary, occurring predominantly in women with germ-line mutations in the BRCA1 or BRCA2 genes. Low expression of these genes in sporadic tumors extends their significance to sporadic breast and ovarian cancers as well. For over a decade since its identification, extensive research has been directed toward understanding the function of the breast and ovarian tumor suppressor gene BRCA1.

A specific RAD51 haplotype increases breast cancer risk in Jewish non-Ashkenazi high-risk women.

While the precise genes involved in determining familial breast cancer risk in addition to BRCA1/2 are mostly unknown, one strong candidate is RAD51. Jewish non-Ashkenazi women at high-risk for breast/ovarian cancer and ethnically matched controls were genotyped using four single nucleotide polymorphisms spanning the RAD51 genomic region, and the resulting haplotypes were constructed using the GERBIL algorithm. A total of 314 individuals were genotyped: 184 non-Ashkenazi high-risk women (119 with breast cancer), and 130 unaffected, average-risk ethnically matched controls.

Adoptive cell therapy for metastatic melanoma patients: pre-clinical development at the Sheba Medical Center.

Background: Metastatic melanoma is an aggressive and highly malignant cancer. The 5 year survival rate of patients with metastatic disease is less than 5% with a median survival of only 6-10 months. Drugs like dacarbazin (DTIC) as a single agent or in combination with other chemotherapy agents have a response rate of 15-30%, but the duration of response is usually short with no impact on survival.

Association between diabetes mellitus and adverse characteristics of breast cancer at presentation.

Type 2 diabetes mellitus is associated with increased incidence and inferior outcome of various malignancies. The aim of this study was to explore the impact of type 2 diabetes on breast cancer characteristics at presentation. The study population included 79 diabetic and 158 age-matched non-diabetic patients.

Hormone replacement therapy is more prevalent among Jewish BRCA1/2 mutation carriers.

The aim of this study was to compare reproductive factors, use of oral contraceptives (OC) and hormone replacement therapy (HRT) in consecutive Jewish Ashkenazi breast cancer patients, with and without BRCA1/BRCA2 mutations. Jewish Israeli women with breast cancer (n=385) were genotyped for the three predominant Jewish mutations in BRCA1 and BRCA2, and data on reproductive factors, OC and HRT use, were analyzed using logistic regression analyses. Overall, 28/385 (7.

Breast conservation after neoadjuvant chemotherapy.

Background: Tumor downstaging by preoperative neoadjuvant chemotherapy in patients with locally advanced breast tumors allows breast conservation in women who were previously candidates for mastectomy. Nevertheless, lumpectomy success in such cases cannot be fully achieved. The aim of this study was to create a quantitative tool for preoperative evaluation of the success of breast conservation in such patients.