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The relationship between reproductive breast risk factors and breast cancer survival in patients with different breast cancer subtypes is not well known.We examined a large-sized, retrospective study of 23,882 subjects from the Korean Breast Cancer Registry. The breast cancer subtype was determined by immunohistochemical staining for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2). Information regarding reproductive factors, including breastfeeding, age at first birth (AFB), and parity, was gathered. Multivariate Cox regression analysis was used to estimate the association among breast cancer subtypes, such as luminal A, luminal B, Her-2/neu overexpressing, and triple negative breast cancer (TNBC), and breast cancer survival as dependent variables and adjusting for age and stage.High parity (≥ 5) increased the recurrence risk of luminal A and B breast cancer (hazard ratio [HR], 1.95; 95% confidence interval [CI], 0.96-3.97; P = .0055 and HR, 1.12; 95% CI, 0.42-3.02, respectively; P = .0073) in breast cancer-specific survival (BCSS), but 1 to 3 child births decreased the recurrence risk of luminal A breast cancer (HR, 0.56; 95% CI, 0.34-0.91; P = .0055) and luminal B breast cancer (HR, 0.32; 95% CI, 0.17-0.61; P = .0073) in BCSS. Early AFB (20 years) increased the recurrence risk of luminal A breast cancers (HR, 1.61; 95% CI, 0.62-4.26; P = .039) in BCSS and of TNBC (HR, 1.31; 95% CI, 0.78-2.21; P = .0006) in overall survival. Her-2/neu overexpressing breast cancer had no correlation with parity and AFB in breast cancer survival.High parity (≥ 5) and early AFB (20 years) were correlated with worse clinical outcomes in patients with luminal breast cancer, but not with other subtyped breast cancers.

Background Despite mounting interest in combination immunotherapy including immune checkpoint inhibitors (ICIs) to improve anti-tumor responses, clinical translation has been disappointing. To address the significant unmet needs remaining, we designed GI101 comprising the extracellular domain of CD80 acting as a dual checkpoint (CTLA4/PD-L1) inhibitor, together with a long acting IL2v that preferentially binds to the IL2Rβ. Methods Affinity of GI101 for IL2Rs, CTLA4, and PD-L1 was determined by SPR. Immune cell proliferation was analyzed by CFSE assay and in vivo immune profiling. In vivo efficacy of GI101 were performed in a tumor-bearing mouse model. Results GI101 exhibits high affinity to both CTLA4 (Kd, 2.9 nM), PD-L1 (Kd, 8.5 nM), and preferential binding to IL2Rβ (Kd, 28.4 nM). GI101 induces the robust stimulation of in vitro and in vivo CD8+ T and NK cell proliferation without a significant increase in Treg cells. GI101 has high binding affinity to CTLA4 acting as a decoy ligand, thereby enhancing the interaction between endogenous CD80 and CD28, leading to the activation of T cells. GI101 elicits improved restoration of immune functions compared to a CD80-Fc in in vitro settings using human PBMCs co-cultured with PD-L1hi tumor cells. In the CT26 tumor-bearing mice, GI101 was superior at inhibiting tumor growth when compared to a combination of aPD-1/aCLTA4 in association with a profound increase in CD8+ T and NK cells without causing an increase in Tregs in the TME. In addition, a dose-dependent anti-tumor effect was observed in CT26 syngeneic models. Furthermore, isolated mortality was observed in the aPD-1/aCTLA4 combo-treated group whereas GI101-treated group has no evidence for toxicity associated with IL2 activity including vascular leakage syndrome and cytokine storm. Conclusions The complementary modes of action of GI101 via dual checkpoint blockade with IL2 activity to enhance the proliferation and activation of Teff and NK cells is projected to translate into superior clinical efficacy and safety as indicated even in ‘cold tumor’ models. GI101 has promising potential to replace first-generation ICIs as a monotherapy or in combination with chemo/radiotherapies and other immunotherapies. Legal entity responsible for the study GI innovation. Funding GI innovation. Disclosure J.C. Park: Shareholder / Stockholder / Stock options, Full / Part-time employment: GI innovation. K.H. Pyo: Research grant / Funding (institution): Yonsei Medical Center. Y.J. Song: Shareholder / Stockholder / Stock options, Full / Part-time employment: GI innovation. W.J. Lee: Shareholder / Stockholder / Stock options, Full / Part-time employment: GI innovation. J. Kim: Shareholder / Stockholder / Stock options, Full / Part-time employment: GI innovation. H.N. Ji: Full / Part-time employment: GI innovation. S.S. Park: Full / Part-time employment: GI innovation. Y.J. Koh: Full / Part-time employment: GI innovation. K. Lee: Shareholder / Stockholder / Stock options, Full / Part-time employment: GI innovation. B. Cho: Research grant / Funding (institution): Yonsei Medical Center. B. Chun: Shareholder / Stockholder / Stock options, Full / Part-time employment: GI innovation. Y.M. Oh: Shareholder / Stockholder / Stock options, Full / Part-time employment: GI innovation. B. Yang: Shareholder / Stockholder / Stock options, Full / Part-time employment: GI innovation. S.Y. Nam: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: GI innovation. M.H. Jang: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: GI innovation.

Background and purpose To evaluate the potential neuroprotection against subsequent cerebral infarction conferred by a prodromal transient ischaemic attack (TIA). Methods Various measures, including blood pressure, blood serum glucose, serum lipids, cardiovascular imaging and changes to NIHSS scores were evaluated upon admission and discharge for patients presenting with ischaemic stroke with or without prodromal TIA (n = 60 per group). Results When all patients from each group were considered together, no significant group effects emerged. However, when the NIHSS difference scores from the prodromal TIA group were subdivided based on (i) prodromal TIA lasting up to 4 min; (ii) two prodromal TIA attacks and/or; (iii) prodromal TIA-stroke interval within 7 days separately, patients in subgroups 1 and 2 exhibited significantly better outcome on discharge. There was no significant effect found in subgroup three although this TIA group did show better outcome in considering the NIHSS changes. Conclusions Prodromal TIA prior to cerebral infarction may result in an ischaemic tolerance effect. Moreover, the neuroprotection conferred by the TIA may be associated with the duration and the frequency of the TIA, although the relationship between the TIA-stroke interval and prognosis is not clear.

Hypomethylation of the O6-methylguanine-DNA-methyltransferase (MGMT) promoter in glioma cells has been associated with temozolomide resistance. S-adenosylmethionine (SAM), which is produced during folate metabolism, is the main source of methyl groups during DNA methylation. As a key enzyme during folate metabolism, polymorphisms of 5,10-methylenetetrahydrofolate reductase (MTHFR) may regulate folate end-products. We investigated the effect of typical polymorphisms of MTHFR (C677T and A1298C) on MGMT methylation based on different serum folate levels in patients with glioma from Northeast China. A total of 275 patients with glioma and 329 without malignant tumors were tested. Serum folate concentration was assayed by using the electrochemiluminescence immunoassay. MTHFR polymorphisms were detected by Taqman-Fluorescence quantitative polymerase chain reaction (PCR). Methylation-specific PCR was used to assess MGMT methylation. The constituent ratio of glioma patients below the serum folate biological reference value was significantly higher than that of the control population (P0.001). In patients with oligodendroglioma and glioblastoma, heterozygotes for the A1298C mutation were found in higher frequency than homozygotes or wild types (oligodendroglioma, P0.001; glioblastoma, P0.01). When grouped by the median or biological reference value of serum folate, only homozygotes for C677T with low levels of folate were significantly associated with decreased methylation of MGMT (median, P0.001; biological reference value, P = 0.036). These data suggest that, in combination with a negative folate balance in glioma patients, T/T genotypes in MTHFR C677T may be associated with MGMT demethylation.

Objective To describe clinical features of patients with multiple sclerosis (MS) in Shanghai, China. Methods Prevalent patients with MS were identified and investigated by a network of physicians in 11 districts of Shanghai during the period from 1 September 2004 to 31 August 2005. Admission registries of each hospital in the study area were checked systematically for patients with a diagnosis of MS, neuromyelitis optica or other demyelinating disorders. All patients with collected information were evaluated by four senior neurologists according to the McDonald criteria. Results There were 249 (146 female and 103 male) patients with a confirmed MS diagnosis, at a female-to-male ratio of 1.4. The mean age at onset of MS was 37.4 years for the 249 patients with MS and, on the prevalence day, 42.7 years. The most frequent location of clinical MS lesions in the central nervous system was the spinal cord (61%), followed by the cerebrum (55%) and optic nerves (41%). Nearly all (96%) of the patients with MS had been examined by magnetic resonance imaging, and 226 (94%) patients of those examined were suggestive of MS. No family history of MS was found in any of the patients. Most (86%) of the patients had no or mild disability on the prevalence day (31 December 2004). Almost all (96%) patients with MS had been treated with corticosteroids. Conclusion Clinical features of patients with MS are described based on the information from the largest case series reported among Chinese. Comparisons and discussions are made with findings from the other populations.

Endometriosis is characterized by an abnormal existence of functional endometrial tissue outside the uterine cavity, typically occuring within the pelvis of women in reproductive age. We report two cases with endometriosis of the abdominal wall; the first one in the rectus abdominis muscle and the second one in the surgical scar of previous caesarean incision along with the rectus abdominis muscle. Pre-operative evaluation included magnetic resonance imaging. The masses were dissected free from the surrounding tissue and excised with clear margins. Diagnosis of the excised lesions were verified by histopathology.