616. The relation between HER2 overexpression on the tumour cells and microvessels density in the tumour stroma in gastric cancer

2016 ◽  
Vol 42 (9) ◽  
pp. S184
Author(s):  
M. Ciesielski ◽  
M. Szajewski ◽  
W.J. Kruszewski ◽  
R. Pęksa ◽  
J. Zieliński ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumour Cells ◽  
Her2 Overexpression ◽  
Tumour Stroma ◽  
Microvessels Density

scholarly journals Tumour-stroma ratio and 5-year mortality in gastric adenocarcinoma: a systematic review and meta-analysis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Niko Kemi ◽  
Maarit Eskuri ◽  
Joonas H. Kauppila
Keyword(s):  
Gastric Cancer ◽  
Prognostic Factor ◽  
Neoadjuvant Therapy ◽  
Cancer Patients ◽  
Gastric Adenocarcinoma ◽  
Meta Analysis ◽  
Prognostic Significance ◽  
Tumour Stroma ◽  
Potential Prognostic Factor ◽  
Gastric Cancer Patients

Abstract Tumour-stroma ratio (TSR) is a novel potential prognostic factor in cancers and based on the proportions of stroma and tumour area. The prognostic value of TSR in gastric cancer is incompletely known. The aim of this study was to estimate prognostic significance of TSR in gastric adenocarcinoma. A search of PubMed (MEDLINE), Web of Science, EMBASE, Cochrane and Scopus databases was performed. A meta-analysis was conducted on five-year survival in gastric cancer patients using inverse variance random-effects methods. The literature search yielded 5329 potential titles, of which a total of seven studies were eligible. Results of six studies including a total of 1779 patients were pooled in the meta-analysis. Only 23 (1.3%) of the patients received neoadjuvant therapy. All six studies had a cut-off of 50% for the proportion of stroma when dividing the patients into low- and high stroma groups. Low TSR (high amount of stroma) was strongly associated with increased five-year mortality (hazard ratio 2.19, 95% CI 1.69–2.85). In conclusion, TSR is a strong prognostic factor in gastric cancer. It could be used to estimate prognosis of gastric cancer patients not receiving neoadjuvant chemotherapy. Further studies including patients receiving neoadjuvant therapy are recommended.

Preclinical activity of MM-111, a bispecific ErbB2/ErbB3 antibody in previously treated ErbB2-positive gastric and gastroesophageal junction cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 48-48 ◽  
Author(s):  
Johanna Lahdenranta ◽  
Violette Paragas ◽  
Arthur J. Kudla ◽  
Ryan Overland ◽  
Victor M. Moyo ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gastroesophageal Junction ◽  
Resistance Mechanism ◽  
Predictive Biomarkers ◽  
Her2 Overexpression ◽  
Multiple Time ◽  
Gastric Cancers ◽  
Treatment Regimens ◽  
Gastroesophageal Junction Cancer ◽  
Erbb3 Signaling

48 Background: ErbB2 (HER2) overexpression has been reported in 7-34% of gastric cancers. ErbB3 (HER3) is the preferred dimerization partner of ErbB2, and ErbB2/ErbB3 heterodimer activation is implicated in the progression and metastasis of ErbB2+ tumors. Activation of ErbB3 signaling is a postulated resistance mechanism to current ErbB2-directed therapies and select chemotherapies. In line with this research, ErbB3 levels are associated with poor prognosis in gastric cancers. MM-111 is a bi-specific antibody that docks to ErbB2 and inhibits ErbB3 signaling in cells that overexpress ErbB2. In this study, MM-111 was evaluated in ErbB2+ gastric cancer by testing the activity of MM-111 in ErbB2+ pre-clinical models of gastric cancer, and by assessing the prevalence of potentially predictive biomarkers in a panel of archived gastric and gastroesophageal junction (GEJ) tumors. Methods: MM-111 was tested in ErbB2+ gastric cancer xenografts that were either untreated or after tumors ceased to respond to trastuzumab/5-FU. Xenografts were analyzed at multiple time points for the expression of ErbB-receptor family members and their downstream signaling by Luminex -assays. Preclinical data indicate that ErbB2, ErbB3, and heregulin are predictive biomarkers for MM-111. In order to determine the prevalence of our potentially predictive biomarkers in gastric and GEJ cancers, we obtained commercially archived tumor tissue and assayed the tissue for ErbB2 and ErbB3 expression levels using quantitative IHC, and measured heregulin transcript levels by RT-PCR. Results: MM-111 synergizes with various treatment regimens in the 2nd line treatment setting in ErbB2+ gastric cancer xenografts. In our models, the combination of MM-111, trastuzumab, and paclitaxel is particularly effective after tumors progressed on trastuzumab/5-FU. MM-111 inhibits the activity of the ErbB –signaling axis in these models. In addition, 23% of GEJ tumor samples and 20% of gastric samples were positive for potentially predictive biomarkers. Conclusions: ErbB2+xenograft tumors that stop responding to trastuzumab-based therapies benefit from MM-111–based regimens.

The clinical analysis of thromboembolism in esophagogastric cancer in Japan: A single institute experience.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 14-14
Author(s):  
Tomoyo Oguri ◽  
Daisuke Takahari ◽  
Yumiko Ota ◽  
Hiroki Osumi ◽  
Izuma Nakayama ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Clinical Stage ◽  
Performance Status ◽  
Squamous Carcinoma ◽  
Clinical Analysis ◽  
Arterial System ◽  
Her2 Overexpression ◽  
Esophagogastric Cancer ◽  
D Dimer

14 Background: Although patients with esophagogastric cancer have a higher risk of thromboembolism (TE), the clinical characteristics of esophagogastric cancer patients with TE remain unclear. Methods: We conducted a retrospective study of who were treated for TE in our institution from January 2014 to August 2017. Results: During this period, 1538 esophaogastic cancer patients received anti cancer therapy. Of these 62 (4.0%) patients diagnosed as having TE during their clinical course. Background of these patitents were median age :64.5 (28-87), gender male/ female: 36 /26, 47 had gastric cancer, 12 esophageal cancer, and 2 gastroesophageal cancer. Performance Status were 0/1/2/3 = 21/24/13/4. Clinical stage were Ⅳ 32 (metastatic sites; lymph nodes 7, peritoneal dissemination 6, ovary 4, liver 1), recurrence 18, and other 12 respectively. 26 patients did not have medical history, 15 had hypertension, 4 had diabetes mellitus, and 4 had hyperlipidemia. Pathologically, adenocarcinoma 50, squamous carcinoma 10, and other 2. Among patients with gastric cancer, 6 (12.8%) showed Her2 overexpression. The median D-dimer levels was 4.81(0.42-17.25) μg/ml. The onset of TE was before starting chemotherapy in 8(12.9%), during receiving chemotherapy in 48(77.4%), and during washout period in 6. On patients who developed TE during receiving chemotherapy, the regimens of chemotherapy were S-1 16, weekly paclitaxel 10 (plus ramucirumab 3), SOX 7, FP 4, Irinotecan 3, SP 3, FOLFOX 3, XP+Trastuzumab3, and others 9. The types of venous thrombosis were deep vein thrombosis 33, pulmonary embolism 23, central venous catheter 7, internal jugular vein 5, subclavian vein 4, and others 5. Four patients suffered cerebral infarction due to thrombosis of the arterial system thrombosis. Initial anticoagulation treatment for TE were heparin 33, warfarin 13, edoxaban 12 and other 4. 29 patients (46.8%) had no symptom related TE. Conclusions: In our analysis, 12.9% patients had TE before starting treatment, we should pay attention to TE immediately after diagnosis of esophagogastric cancer. As 46.8% patients have no symptom related TE, it is important to develop of biomarkers for screening TE, likely D-dimer.

Safety, pharmacokinetics, and efficacy of RC48-ADC in a phase I study in patients with HER2-overexpression advanced solid cancer.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 334-334
Author(s):  
Jifang Gong ◽  
Jianmin Fang ◽  
Lin Shen
Keyword(s):  
Gastric Cancer ◽  
Dose Escalation ◽  
Solid Tumor ◽  
Urothelial Cancer ◽  
Stage Iv ◽  
Her2 Overexpression ◽  
Solid Cancer ◽  
Open Label ◽  
Expansion Stage ◽  
Wbc Count

334 Background: HER2 overexpression is common in many malignancies and contributes to tumor growth. Unlike the varied options of anti-HER2 target therapies for breast cancer, there is a huge unmet medical need for HER2 overexpressing non-breast solid tumor (NBST) such as gastric cancer and urothelial cancer. Therefore, we conducted the first study of RC48-ADC, a novel humanized anti-HER2 antibody conjugate, in NBST. Methods: This was an open-label, dose-escalation and expansion study in patients with HER2-overexpression (IHC 2+ and 3+) advanced solid cancers after failure of standard treatment. The dose escalation consisted of accelerated (0.1 and 0.5 mg/kg) and “3+3” titrations (1.0, 2.0, 2.5 and 3.0 mg/kg). In dose expansion stage, patients were given RC48-ADC at 2.0 mg/kg, Q2W. Results: As of Aug 20, 2019, 57 patients (including 47 with gastric cancer and 4 with urothelial cancer) were treated at 0.1 (1 patient), 0.5 (1 patient), 1.0 (3 patients), 2.0 (6 patients in dose escalation and 32 patients in dose expansion), 2.5 (11 patients), and 3.0 mg/kg (3 patients), respectively. Most of them were Stage IV (91.2%) or with metastasis (96.5%). DLT was observed in 1, 2, and 1 patient at 2.0, 2.5, and 3.0 mg/kg, respectively. The MTD was 2.5 mg/kg. Most commonly reported TRAEs were WBC count decreased (66.7%), fatigue (56.1%), neutrophil count decreased (54.4%) and hemoglobin decreased (52.6%). Grade 3/4 TRAEs were reported in 28 patients (49.1%). Confirmed ORR was 21.1% (8/38) for 2.0 mg/kg, and 17.5% (10/57) for all patients. DCR was 52.6% and 49.1%, respectively. PFS was 3.6 months (95% CI: 4.1, 11.3) for 2.0 mg/kg. Subgroup ORR was 20.7% (6/29) at 2.0 mg/kg and 18.2% (2/11) at 2.5 mg/kg for gastric cancer, and 50.0% (2/4) for urothelial cancer. Conclusions: RC48-ADC demonstrated a good safety profile and promising anti-tumor activity in the late stage solid tumor including gastric cancer and urothelial cancer. Response and PFS benefits were clinical meaningful at 2.0 mg/kg and 2.5 mg/kg. Phase 2 pivotal study (NCT03556345) in gastric cancer is ongoing. Clinical trial information: NCT02881190.

Clinicopathological and prognostic significance of HER2 overexpression in gastric cancer: a meta-analysis of the literature

Tumor Biology ◽  
2014 ◽  
Vol 35 (5) ◽  
pp. 4849-4858 ◽  
Author(s):  
Ji-wang Liang ◽  
Jian-jun Zhang ◽  
Tao Zhang ◽  
Zhi-chao Zheng
Keyword(s):  
Gastric Cancer ◽  
Meta Analysis ◽  
Prognostic Significance ◽  
Her2 Overexpression

scholarly journals Correlations of Human Epithelial Growth Factor Receptor 2 Overexpression with MUC2, MUC5AC, MUC6, p53, and Clinicopathological Characteristics in Gastric Cancer Patients with Curative Resection

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Kwang Kuk Park ◽  
Song I Yang ◽  
Kyung Won Seo ◽  
Ki Young Yoon ◽  
Sang Ho Lee ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Growth Factor Receptor ◽  
Clinicopathological Characteristics ◽  
Her2 Overexpression ◽  
Her2 Expression ◽  
Her2 Positive ◽  
Poor Prognostic Factor ◽  
P53 Expression ◽  
Gastric Cancer Patients

Background. The purpose of this study was to evaluate the relationships between HER2 overexpression in the tumor and MUC2, MUC5AC, MUC6, and p53 status and clinicopathological characteristics of gastric cancer patients.Methods. This retrospective study included 282 consecutive patients with gastric cancer who underwent surgery at the Kosin University Gospel Hospital between April 2011 and December 2012. All tumor samples were examined for HER2 expression by immunohistochemistry (IHC) and MUC2, MUC5AC, MUC6, and p53 expression by staining. A retrospective review of the medical records was conducted to determine the correlation between the presence of HER2 overexpression and clinicopathological factors.Results. The HER2-positive rate was 18.1%. Although no association was found between HER2 expression and MUC5AC, the expression of MUC2, MUC6, and p53 was significantly correlated with HER2 positivity, respectively (P= 0.004, 0.037, 0.002). Multivariate analysis revealed that HER2 overexpression and nodal status were independent prognostic factors.Conclusions. HER2 overexpression in gastric carcinoma is an independent poor prognostic factor.

scholarly journals Clinicopathologic Features Predicting HER2 Overexpression in Gastric Cancer

2013 ◽  
Vol 24 ◽  
pp. ix15
Author(s):  
J.S. Park ◽  
S. Lim ◽  
H.J. Chon ◽  
M.H. Hong ◽  
B. Kang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Her2 Overexpression ◽  
Clinicopathologic Features
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