Guidance of sentinel lymph node biopsy decisions in patients with T1-T2 melanoma using gene expression profiling.

AIM: Can gene expression profiling be used to identify patients with T1-T2 melanoma at low risk for sentinel lymph node (SLN) positivity? PATIENTS & METHODS: Bioinformatics modeling determined a population in which a 31-gene expression profile test predicted \u3c5% SLN positivity. Multicenter, prospectively-tested (n = 1421) and retrospective (n = 690) cohorts were used for validation and outcomes, respectively. RESULTS: Patients 55-64 years and ≥65 years with a class 1A (low-risk) profile had SLN positivity rates of 4.9% and 1.6%. Class 2B (high-risk) patients had SLN positivity rates of 30.8% and 11.9%. Melanoma-specific survival was 99.3% for patients ≥55 years with class 1A, T1-T2 tumors and 55.0% for class 2B, SLN-positive, T1-T2 tumors. CONCLUSION: The 31-gene expression profile test identifies patients who could potentially avoid SLN biopsy

CD4+ and CD8+ T cells have opposing roles in breast cancer progression and outcome

The Cancer Immunoediting concept has provided critical insights suggesting dual functions of immune system during the cancer initiation and development. However, the dynamics and roles of CD4(+) and CD8(+) T cells in the pathogenesis of breast cancer remain unclear. Here we utilized two murine breast cancer models (4T1 and E0771) and demonstrated that both CD4(+) and CD8(+) T cells were increased and involved in immune responses, but with distinct dynamic trends in breast cancer development. In addition to cell number increases, CD4(+) T cells changed their dominant subsets from Th1 in the early stages to Treg and Th17 cells in the late stages of the cancer progression. We also analyzed CD4(+) and CD8(+) T cell infiltration in primary breast cancer tissues from cancer patients. We observed that CD8(+) T cells are the key effector cell population mediating effective anti-tumor immunity resulting in better clinical outcomes. In contrast, intra-tumoral CD4(+) T cells have negative prognostic effects on breast cancer patient outcomes. These studies indicate that CD4(+) and CD8(+) T cells have opposing roles in breast cancer progression and outcomes, which provides new insights relevant for the development of effective cancer immunotherapeutic approaches

Hypoglycemia with a large retroperitoneal mass – Case report

INTRODUCTION: Retroperitoneal sarcomas have rarely been reported to secrete insulin-growth factor II (IGF-II) and produce an enigmatic hypoglycemia. IGF-II-secreting sarcomas represent an extremely rare subset of soft tissue tumors, and reports are limited to a handful of cases. PRESENTATION OF CASE: The authors present the case of hypoglycemia due to an IGF-II-secreting retroperitoneal sarcoma that was successfully treated by complete surgical resection. This report describes the diagnosis and management of this rare syndrome with 1-year follow-up and a review of the literature. DISCUSSION: Steroid and growth hormone therapies also have efficacy to treat this hypoglycemia in some patients. However, outcomes appear better if combined with surgical resection. CONCLUSIONS: The findings of this case report and review of the literature support a primary role for complete tumor resection to address tumor-induced hypoglycemia

Anti-miR-203 Upregulates SOCS3 Expression in Breast Cancer Cells and Enhances Cisplatin Chemosensitivity

Breast cancer is one of the most common cancers among women in the United States. Although there are effective drugs, such as cisplatin, for treating advanced cancers, many patients eventually develop resistance. MicroRNAs (miRNAs) have emerged to play important roles in tumorigenesis and drug resistance. In this study, the authors observed a significant upregulation of miR-203 expression in human breast cancer tissues as compared to patient-matched nontumor breast tissues. Knockdown of miR-203 following cisplatin treatment enhances p53, p21, and Bax protein expression. Furthermore, knockdown of miR-203 sensitized human breast cancer MCF-7 cells to cisplatin-mediated apoptotic cell death, as evident from caspase-9 and caspase-7 activation, and poly(ADP-ribose) polymerase (PARP) cleavage. Moreover, the authors have demonstrated that suppressor of cytokine signaling 3 (SOCS3) is a novel target of miR-203, and cisplatin treatment in miR-203 knockdown MCF-7 cells enhanced SOCS3 expression. Exogenous expression of SOCS3 in MCF-7 cells increased sensitization to cisplatin-mediated apoptosis. Together, the results suggested a novel role of miR-203 in conferring cisplatin resistance through suppression of SOCS3, implicating an additional therapeutic strategy may be helpful to overcome cisplatin resistance for breast cancer patients