Claudin 18.2 expression in various tumor types and its role as a potential target in advanced gastric cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 80-80
Author(s):  
Jang Ho Cho ◽  
Sung Won Lim ◽  
Seung Tae Kim ◽  
Jeeyun Lee ◽  
Se Hoon Park ◽  
...  

80 Background: Alterations in claudin expression can impair tight junction functioning, influence signaling pathways, and act as a tumor promoting event in some epithelial cancers. Recently, IMAB362, a highly potent and tumor cell-selective therapeutic antibody to claudin 18.2, has been developed and investigated in clinical trials. Methods: We prospectively conducted claudin 18.2 immunohistochemistry on 430 consecutive patients with advanced gastrointestinal, genitourinary, or rare cancers between June 2012 and March 2016. Results: Most patients (414/430, 96.2%) were evaluable for claudin 18.2 expression by immunohistochemistry. In total, 4.1% (17/414) were deemed claudin 18.2+, including patients with pancreatic (16.7%, 1 of 6), gastric (14.1%, 12 of 85), biliary tract (6.3%, 1 of 16), genitourinary/miscellaneous (2.2%, 1 of 46), and colorectal (0.9%, 2 of 203) cancers. Twelve of 17 patients positive for claudin 18.2 had gastric cancers; this subgroup showed no statistical difference by gender, age, disease extent, primary tumor site, pathologic differentiation, HER2 status, or EBV status with or without claudin 18.2 expression. However, claudin 18.2 was more frequently positive in intestinal-type compared to diffuse-type by Lauren classification (p = 0.026). There was no significant difference in overall survival between patients with and without claudin 18.2 expression (p = 0.101). Conclusions: Our results add to the emerging literature on claudin 18.2 expression in various cancer types and support the need for extended clinical exploration of IMAB362.

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1070-1070
Author(s):  
Shafia Rahman ◽  
Juan Trias ◽  
Margarita Kushnir ◽  
Henny H. Billett

Abstract Introduction: DOACs are absorbed in the gastrointestinal (GI) tract and DOAC elimination is primarily through the GI and genitourinary (GU) systems. The safety of DOACs in cancer associated thrombosis in subjects with malignant lesions in GI and GU malignancies has been of concern. Studies have been sparse and data conflicting. Methods: We identified patients with active GI and GU malignancies from July 2001 to July 2020 with confirmed VTE at our institution. Patients who received either enoxaparin or a DOAC (apixaban or rivaroxaban) were included in the study. Demographic, disease characteristics, VTE data and events were extracted from electronic medical records (EMR). Date of anticoagulation (AC) initiation was based on the first order and/or prescription of the anticoagulant. Patients were followed either to the earliest bleeding event (BE) or one year from initiation, whichever occurred first. BEs were categorized based on ISTH guidelines. Variables were compared between LMWH and DOAC cohorts, as well as between the apixaban and rivaroxaban cohorts, using t-tests for continuous variables and chi-squared tests or Fisher's exact test for categorical variables. Results: We identified a total of 206 patients, 159 in the DOAC and 47 in the LWMH groups. Table 1 describes the baseline characteristics of the study populations. Median age of patients, gender and BMI were comparable for all groups. When evaluated for type of cancer, 66.6% of patients had active GI malignancy while 33.3% had active GU tumors. The majority of the patients given DOACs had a better ECOG status than those in the LMWH group (p=0.0023), but no difference was noted for ECOG status between DOACs (p=0.69). Most patients had metastatic disease. The majority of the VTE events were in the form of DVTs. Concomitant aspirin intake was 9.4% in DOAC and 4.2% in LMWH groups. Cancer subtypes and AC choice data are given in detail in Table 2. LMWH use was higher in blacks and somewhat lower in the Hispanic population (Table 1). When anticoagulation choice was examined by primary tumor site (Table 2), disproportionately more patients with GU tumors were placed on LMWH while more GI cancers were given a DOAC (p=0.014). Extent and stage of the cancer did not appear to bias anticoagulant choice (p=0.62). Within the DOACs, rivaroxaban use was higher in the GI cancers but considerably less used in the GU malignancies (p=0.00049). There was one recurrent thrombosis in each of the apixaban (1/86) and the rivaroxaban (1/73) cohorts. There were no recurrent events in the LMWH (0/47) cohort. The majority of patients in the DOAC and LMWH groups, 88.1% and 86.4%, had no CRNMB or major bleeding events in the 1-year period after the initiation of the therapeutic AC (Table 3). Combined BE (clinically relevant non-major bleeding [CRNMB] and major bleeding rates) with apixaban, rivaroxaban and LMWH were 17.4% (15/86), 20.5% (15/73), and 19.1% (9/47) respectively. There were no fatal bleeding episodes in any of the groups. Most of the bleeding events on DOACs and LMWHs occurred in the same organ system as the primary cancer (Table 3) but there was no statistically significant difference in bleeding events between patients on DOACs or LMWH for GI, GU or all cancer types (p=0.63, 0.75 and 0.97 respectively). Within DOACs, we also noted no statistically significant difference in the bleeding events with apixaban as compared to rivaroxaban in patients with GI primary, GU primary or all cancer types together, (p=0.47, 0.94 and 0.62 respectively). Conclusion: No significant differences in major/CRNM bleeding events were found for patients with GI or GU cancer associated thrombosis given DOACs (apixaban/rivaroxaban) vs enoxaparin. The tumor site is often the site of bleeding, but no differences in tumor-specific site bleeding could be shown by anticoagulant choice. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.


1997 ◽  
Vol 15 (8) ◽  
pp. 2792-2799 ◽  
Author(s):  
A Gajjar ◽  
R A Sanford ◽  
R Heideman ◽  
J J Jenkins ◽  
A Walter ◽  
...  

PURPOSE To evaluate the impact of primary tumor site, age at diagnosis, extent of resection, and histology on progression-free survival (PFS) in pediatric low-grade astrocytoma. PATIENTS AND METHODS Medical, pathologic, and imaging information were reviewed for 142 children (ages 2 months to 19 years) with low-grade astrocytoma treated between January 1984 and July 1994. Gross total resection (GTR) was attempted for cerebellar and cerebral hemisphere tumors, with biopsy or less aggressive resection used predominantly for tumors in other sites. Surgery was followed by observation in 107 cases, radiation therapy in 31, and chemotherapy in four. RESULTS The overall survival rate was 90% +/- 3% (SE) at 4 years. PFS was significantly better for patients with cerebellar and cerebral hemisphere tumors (n = 75) than those with tumors in all other sites (P = .0006). Within the former group, there was no significant difference in PFS for patients in whom GTR was achieved versus those with incomplete resections (4-year estimates, 89% and 77%, respectively). Histology (juvenile pilocytic v astrocytoma not otherwise specified [NOS]) was not related to PFS in an analysis that controlled for tumor site and patient age. Patients younger than 5 years at diagnosis had a significantly poorer PFS than older children, regardless of histology (P < .03) or tumor site (P < .002). Treatment for progressive/recurrent disease was effective in a majority of patients, but appeared more successful in patients with hemispheric than thalamic or hypothalamic tumors. CONCLUSION The overall survival in this series of pediatric low-grade astrocytomas is excellent. Age at diagnosis and tumor location, but not histology, had a significant impact on PFS. Efforts to improve treatment outcome should focus on young patients (< 5 years) and on those with central midline tumors. The majority of patients with completely resected hemispheric tumors were monitored without further therapy, which supports attempted GTR of cerebral and cerebellar hemisphere low-grade astrocytoma.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e21046-e21046
Author(s):  
Amy Little Jones ◽  
Aron Joon ◽  
Lauren Elaine Haydu ◽  
Alexander J. Lazar ◽  
Michael T. Tetzlaff ◽  
...  

e21046 Background: Overall survival (OS) for pts with cutaneous melanoma has vastly improved with checkpoint inhibitors (CPI) and targeted therapy (TT), but less is known about outcomes of other rare tumors showing melanocytic differentiation. We examined outcomes for metastatic pts with MSP/CCS at MD Anderson (MDA) to characterize outcomes with contemporary therapies. Methods: Pts with MSP/CCS were identified in the MDA databases. Pts with < 2 visits to MDA or without molecular confirmation of dx were excluded. Log-rank testing was used to compare OS among distributions. Results: A total of 102 MSP/CCS pts were identified. Initial diagnosis was local disease 46%, regional metastases 34%, and systemic metastases 20%. Primary tumor site was lower extremity (LE) 48%, GI tract 29%, upper extremity (UE) 18%. 65 pts were diagnosed with metastatic disease (dz), including 32% with lung-only, 14% liver-only, and 51% with multiple metastatic sites. Median OS from diagnosis of distant metastatic dz was 22 mos (95% CI 16-34 mos). Primary tumor site (GI 46.4 vs. LE 19.1 vs. UE 14.7 mos; p = 0.018) and race (white 26.8 vs. black 6.5 mos, p = 0.019, HR 0.45) were significantly associated with OS from distant metastasis; sex, age, decade of diagnosis, size of primary, and prior treatment with neoadjuvant or adjuvant therapy were not. Treatments for metastatic dz included chemotherapy (n = 29), biochemotherapy (n = 11), biotherapy (n = 5), CPI (n = 11) and TT (n = 19). Median OS was 15.9 mos from start of CPI (range 10.7 to NR) and 16.9 mos from start of TT (range 7.8 to NR). Median OS from metastatic dz for pts not treated with CPI or TT was 17.1 mos (range 12.4 to 32.5), which was not significantly different versus CPI or TT. Duration of response was < 6 mos for 91% pts receiving CPI and 89% pts receiving TT. One pt had a durable response (41.8 mos) to anti-PD1 and one pt had a durable response (24.8 mos) to an AKT inhibitor. Conclusions: While rare responses to CPI and TT were observed, no significant difference was detected in OS compared to traditional therapies in pts with metastatic MSP/CCS. The development of more effective therapies remains an unmet need for this disease.


2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 213-213
Author(s):  
Sang Eun Yoon ◽  
Jung Hoon Kim ◽  
Joon Young Hur ◽  
Su Jin Lee ◽  
Jeeyun Lee ◽  
...  

213 Background: Gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC) is a heterogeneous disease in terms of embryonic origin, aggressiveness, prognosis, and genomic profiling. Data regarding the efficacy of etoposide and cisplatin (EP) as a standard treatment of the primary tumor site in GEP-NEC are limited. Methods: We analyzed 64 patients with histopathologically confirmed metastatic GEP-NEC who received EP at Samsung Medical Center, Seoul, Korea, between January 2010 and January 2018. Based on primary tumor site, outcome of treatment with EP was evaluated. Results: Primary sites included 22 foregut-derived GEP-NECs (stomach, n = 6; duodenum, n = 4; pancreas, n = 12), 4 midgut-derived GEP-NECs, 5 hindgut-derived GEP-NECs of the rectum, 25 GEP-NECs originating from the hepatobiliary (HB) tract, and 12 GEP-NECs involving only intra-abdominal lymph nodes. No patient had a complete response (CR) and 17 had a partial response (PR), resulting in a 27.9% response rate (RR). When evaluating the efficacy of EP based on primary tumor site, the RR was most favorable in GEP-NECs involving only intra-abdominal lymph nodes, followed by GEP-NECs originating from foregut, midgut, HB, and hindgut. However, no statistically significant difference was observed for RR based on primary tumor site (p = 0.821). Similarly, no significant differences were found for progression-free survival (PFS) among patients with GEP-NECs arising from various primary tumor sites. Conclusions: Results from this study showed thatRR and PFS associated with EP treatment were not different based on the primary tumor site in patients with advanced or metastatic GEP-NEC.


2009 ◽  
Vol 16 (3) ◽  
pp. 663-673 ◽  
Author(s):  
David Vindrieux ◽  
Pauline Escobar ◽  
Gwendal Lazennec

Prostate cancer (PCa) represents the second leading cause of death among all cancer types in men in Europe and North America. Among the factors suspected to control PCa, incidence and progression, chemokines, and their receptors are now intensively studied. Chemokines are produced by tumor cells and also by the stromal microenvironment, both in the primary tumor site and in distant metastatic locations. The wide and differential distribution of chemokines and their receptors account for the pleiotropic actions of chemokines in PCa, including the modulation of growth, angiogenesis, invasion, metastasis, and hormone escape. This review will focus on the roles and the mechanisms of action and regulation of chemokines in the different steps of PCa development and will discuss the novel strategies that are currently envisioned to target chemokines in PCa.


2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 160-160
Author(s):  
Ferdinando De Vita ◽  
Michele Orditura ◽  
Alessio Fabozzi ◽  
Maria Maddalena Laterza ◽  
Jole Ventriglia ◽  
...  

160 Background: HER2 overexpression in GC is reported in 20% of cases; it is considered a negative prognostic factor with a positive predictive value of response to trastuzumab. We reviewed our case records analyzing its clinical significance. Methods: We retrospectively collected the data for patients (pts.) with histologically confirmed GC and tumor specimens. Results: From June 2011 to December 2012 we analyzed HER2 status in 76 pts with metastatic GC. (M/F 50/26, median age 64 years, ECOG performance status 0/1/2 = 59/12/5, G1/G2/G3 = 6.6%/22.4%/71%). In 36.8% of pts. gastric body was the primary tumor site. HER-2 overexpression was observed in 13 pts (17.1%). HER2-positive group had the following characteristics: M/F = 10/3, median age 63 years; Lauren’s histotype: 75% intestinal and 25% diffuse; G1/G2/G3 = 15.4%/30.8%/53.8%; T3-T4 tumors and N+ disease were observed in 46.1% respectively; the primary tumor site was: proximal 38.4%, distal 61.6%. 46.1% of pts with metastatic disease received a first line CT with a median progression free survival (mPFS) of 5 months (range, 3-7) and a median overall survival (mOS) of 9 months (range, 3-23). In HER2-negative group, (N= 63, M/F = 40/23, median age 64 years), 92.1% of pts. Lauren’s histotype: 45.5% intestinal and 54.5% diffuse; G1/G2/G3 = 4.8%/20.6%/74.6%; metastatic disease: 55.5%. T3-T4 tumors were assessed in 65.1% of pts and N+ disease in 61.9%. The primary tumor location was: proximal 38.1%, distal 61.9%. 57.1% with advanced disease received a first line CT with a mPFS of 5.5 months (range, 2-30) and a mOS of 10 months (range, 2-67). No statistically significant differences for mPFS (p: 0.08) and mOS (p: 0.06) were observed between HER2 positive and HER2 negative metastatic patients. Conclusions: According to our experience, HER2 overexpression doesn’t seem to correlate with a worse prognosis. In particular, it is not correlated with a worse histology and higher stage at diagnosis. Furthermore, no differences in terms of mPFS and mOS were observed between HER2 positive and HER2 negative metastatic pts.


1996 ◽  
Vol 14 (5) ◽  
pp. 1537-1544 ◽  
Author(s):  
M Guglielmi ◽  
B De Bernardi ◽  
A Rizzo ◽  
S Federici ◽  
C Boglino ◽  
...  

PURPOSE To determine whether resection of primary tumor has a favorable influence on outcome of infants (age 0 to 11 months) with stage IV-S neuroblastoma. PATIENTS AND METHODS Between March 1976 and December 1993, 97 infants with previously untreated neuroblastoma diagnosed in 21 Italian institutions were classified as having stage IV-S disease. Seventy percent were younger than 4 months. Adrenal was the primary tumor site in 64 of 85 patients with a recognizable primary tumor. Liver was the organ most often infiltrated by the tumor (82 patients), followed by bone marrow and skin. RESULTS The overall survival (OS) rate at 5 years in 80% and event-free survival (EFS) rate 68%. In 24 infants, the effect of resection of primary tumor could not be evaluated because of rapidly fatal disease progression (n = 8), absence of a primary tumor (n = 12), or partial resection (n = 4). Of 73 assessable patients, 26 underwent primary tumor resection at diagnosis: one died of surgical complications, one relapsed locally and died, and two others relapsed (one of these two locally) and survived, for a 5-year OS rate of 92% and EFS rate of 84%. Of the remaining 47 patients who did not undergo primary tumor resection at diagnosis 11 suffered unfavorable events, of whom five died, for an OS rate of 89% and EFS rate of 75% (no significant difference from previous group). Disease recurred at the primary tumor site in only one five who died, and in only one of six survivors of progression or relapse; in these patients, the primary tumor, located in the mediastinum, was successfully resected. CONCLUSION Infants who underwent resection of the primary tumor at diagnosis had no better outcome than those in whom the decision was made not to operate.


Author(s):  
Syoof Khowman Alramahy ◽  
Akram Hadi Hamza

This study was carried out to study of some immunological aspects among the pulmonary Tuberculosis patients infected with causative agent, Mycobacterium tuberculosis. A Total of 200 sputum samples were collected from patients attending the consultant Clinic for Chest and Respiratory disease center, Diwaniya. Control group (No=15) also included. According to acid fast stain of sputum, the patients were classified as positive (No=91,45.5%) and negative (No=109,54.5, Lowenstein Jensen medium used for the cultivation of samples, on which 70% of sputum samples where positive culture for this microorganism. The grown microorganism were identified as M. tuberculosis, based on positive A.F.B, Niacin producers ,negative for catlase at 68c. The mean IgG level was l184.053±76.684 mg/100 ml in tuberculosis group compared with 1016.533 ± 44.882 mg/100ml in control group, rendering the statistical difference significant. For IgA and IgM levels, they were at mean of 315.880±38.552 mg/100 ml and 119.527±8.464 mg/100 ml in control group compared with 396.358±38.776 mg/100 ml and 134.207±11.696 mg/100 ml in patients group respectively with significant difference


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Qin Huo ◽  
Zhenwei Li ◽  
Siqi Chen ◽  
Juan Wang ◽  
Jiaying Li ◽  
...  

Abstract Purpose Von Willebrand Factor C and EGF Domains (VWCE) is an important gene that regulates cell adhesion, migration, and interaction. However, the correlation between VWCE expression and immune infiltrating in breast cancer remain unclear. In this study, we investigated the correlation between VWCE expression and immune infiltration levels in breast cancer. Methods The expression of VWCE was analyzed by the tumor immune estimation resource (TIMER) and DriverDB databases. Furthermore, genes co-expressed with VWCE and gene ontology (GO) enrichment analysis were investigated by the STRING and Enrichr web servers. Also, we performed the single nucleotide variation (SNV), copy number variation (CNV), and pathway activity analysis through GSCALite. Subsequently, the relationship between VWCE expression and tumor immunity was analyzed by TIMER and TISIDB databases, and further verified the results using Quantitative Real-Time PCR (RT-PCR), Western blotting, and immunohistochemistry. Results The results showed that the expression of VWCE mRNA in breast cancer tissue was significantly lower than that in normal tissues. We found that the expression level of VWCE was associated with subtypes, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status of breast cancer patients, but there was no significant difference in the expression of VWCE was found in age and nodal status. Further analyses indicated that VWCE was correlated with the activation or inhibition of multiple oncogenic pathways. Additionally, VWCE expression was negatively correlated with the expression of STAT1 (Th1 marker, r = − 0.12, p = 6e−05), but positively correlated with the expression of MS4A4A (r = 0.28, p = 0). These results suggested that the expression of VWCE was correlated with immune infiltration levels of Th1 and M2 macrophage in breast cancer. Conclusions In our study, VWCE expression was associated with a better prognosis and was immune infiltration in breast cancer. These findings demonstrate that VWCE is a potential prognostic biomarker and correlated with tumor immune cell infiltration, and maybe a promising therapeutic target in breast cancer.


1995 ◽  
Vol 13 (6) ◽  
pp. 1368-1376 ◽  
Author(s):  
D G Tubergen ◽  
M D Krailo ◽  
A T Meadows ◽  
J Rosenstock ◽  
M Kadin ◽  
...  

PURPOSE Patients with lymphoblastic non-Hodgkin's lymphoma (LB NHL) were randomized to treatment with either modified LSA2L2 or ADCOMP, which added daunorubicin (DAUN) and asparaginase (L-ASP) to the methotrexate (MTX), cyclophosphamide (CYT), vincristine (VCR), and prednisone (PRED) (COMP) regimen, in a clinical trial to determine the relative effectiveness and toxicity of the two regimens. PATIENTS AND METHODS Patients with LB NHL were eligible for this randomized study if they were less than 22 years of age at diagnosis and had < or = 25% blasts in the bone marrow. Of 307 patients registered, 281 were fully eligible and assessable. Patients were stratified by extent of disease at diagnosis. RESULTS The 5-year event-free survival (EFS) rate for patients with localized disease was 84%, and for patients with disseminated disease, 67%. There were four relapses in 28 patients with localized disease. Two hundred six patients had mediastinal primary tumors and despite local radiation, 34 of 63 failures in these patients involved the primary tumor site with or without other involvement. After adjusting for extent of disease at diagnosis, the regimens did not differ significantly with respect to risk for adverse events. The acute toxicity was primarily neutropenia and thrombocytopenia, with greater initial toxicity in patients on the LSA2L2 regimen. Three patients developed acute myelogenous leukemia. CONCLUSION Long-term EFS in children with LB NHL can be achieved in the majority of patients. Disease progression, which includes recurrence at the primary tumor site, is a major cause of treatment failure in patients with mediastinal presentations. Addition of DAUN and L-ASP to the COMP regimen does not produce a more effective treatment than LSA2L2.


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