Enhanced Primary Tumor Penetration Facilitates Nanoparticle Draining into Lymph Nodes after Systemic Injection for Tumor Metastasis Inhibition

ACS Nano ◽  
2019 ◽  
Vol 13 (8) ◽  
pp. 8648-8658 ◽  
Author(s):  
Jing Liu ◽  
Hong-Jun Li ◽  
Ying-Li Luo ◽  
Cong-Fei Xu ◽  
Xiao-Jiao Du ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Primary Tumor ◽  
Tumor Metastasis ◽  
Systemic Injection ◽  
Tumor Penetration ◽  
Metastasis Inhibition

scholarly journals A Pro-Tumorigenic Effect of Heparanase 2 (Hpa2) in Thyroid Carcinoma Involves Its Localization to the Nuclear Membrane

2021 ◽  
Vol 11 ◽  
Author(s):  
Itai Margulis ◽  
Inna Naroditsky ◽  
Miriam Gross-Cohen ◽  
Neta Ilan ◽  
Israel Vlodavsky ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Lymph Nodes ◽  
Nuclear Membrane ◽  
Tumor Metastasis ◽  
Cellular Localization ◽  
Thyroid Tissue ◽  
Clinicopathological Parameters ◽  
Regional Lymph Nodes ◽  
Normal Thyroid

Activity of the endo-beta-glucuronidase heparanase, capable of cleaving heparan sulfate (HS), is most often elevated in many types of tumors, associating with increased tumor metastasis and decreased patients’ survival. Heparanase is therefore considered to be a valid drug target, and heparanase inhibitors are being evaluated clinically in cancer patients. Heparanase 2 (Hpa2) is a close homolog of heparanase that gained very little attention, likely because it lacks HS-degrading activity typical of heparanase. The role of Hpa2 in cancer was not examined in detail. In head and neck cancer, high levels of Hpa2 are associated with decreased tumor cell dissemination to regional lymph nodes and prolonged patients’ survival, suggesting that Hpa2 functions to attenuate tumor growth. Here, we examined the role of Hpa2 in normal thyroid tissue and in benign thyroid tumor, non-metastatic, and metastatic papillary thyroid carcinoma (PTC) utilizing immunostaining in correlation with clinicopathological parameters. Interestingly, we found that Hpa2 staining intensity does not significantly change in the transition from normal thyroid gland to benign, non-metastatic, or metastatic thyroid carcinoma. Remarkably, we observed that in some biopsies, Hpa2 is accumulating on the membrane (envelop) of the nucleus and termed this cellular localization NM (nuclear membrane). Notably, NM localization of Hpa2 occurred primarily in metastatic PTC and was associated with an increased number of positive (metastatic) lymph nodes collected at surgery. These results describe for the first time unrecognized localization of Hpa2 to the nuclear membrane, implying that in PTC, Hpa2 functions to promote tumor metastasis.

GEWF Solution

2001 ◽  
Vol 125 (5) ◽  
pp. 642-645 ◽  
Author(s):  
Ken J. Newell ◽  
Barry W. Sawka ◽  
Brian F. Rudrick ◽  
David K. Driman
Keyword(s):  
Colorectal Cancer ◽  
Lymph Nodes ◽  
Glacial Acetic Acid ◽  
Bowel Wall ◽  
Health Centre ◽  
Lymph Node Status ◽  
Regional Health ◽  
Tumor Penetration ◽  
Colorectal Cancer Resection ◽  
Positive Lymph Nodes

Abstract Background.—Lymph node status is an important prognostic factor in the staging of colorectal carcinoma. Several adjunctive solutions have been used to increase the yield of pericolic lymph nodes from colorectal cancer resection specimens. Methods.—During 1998 at the Grey Bruce Regional Health Centre (Owen Sound, Ontario), 67 colonic resections were performed for colorectal cancer. Lymph nodes were identified using GEWF solution (glacial acetic acid, ethanol, distilled water, and formaldehyde) in 35 cases, and by the conventional method of sectioning, inspection, and palpation in 32 cases. Results.—There were no significant differences between GEWF and non-GEWF cases with respect to patient age, length of resection, size of tumor, tumor histologic type, tumor differentiation, or depth of tumor penetration into the bowel wall. Use of GEWF led to a significant increase in the number of lymph nodes found (10.2 ± 4.9 per case) compared with non-GEWF cases (6.8 ± 3.9 per case) (P = .002). In GEWF cases 358 lymph nodes were identified, 82 with metastases, whereas in the non-GEWF cases 218 lymph nodes were found, 41 with metastases. The size of positive lymph nodes in the GEWF group (0.5 ± 0.2 cm) was significantly smaller than in the non-GEWF group (0.7 ± 0.4 cm) (P = .046). A greater percentage of positive lymph nodes in the GEWF cases (49/82, 60%) were 0.5 cm or smaller compared with the non-GEWF cases (17/41, 41%). Conclusions.—GEWF increases the yield of lymph nodes recovered from colorectal cancer specimens and may lead to improved staging of this cancer; it is inexpensive and simple to use.

Predictors of Local-Regional Recurrence After Neoadjuvant Chemotherapy and Mastectomy Without Radiation

2002 ◽  
Vol 20 (1) ◽  
pp. 17-23 ◽  
Author(s):  
Thomas A. Buchholz ◽  
Susan L. Tucker ◽  
Lawrence Masullo ◽  
Henry M. Kuerer ◽  
Jessica Erwin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Lymph Nodes ◽  
Primary Tumor ◽  
Clinical Stage ◽  
Pathologic Complete Response ◽  
Hazard Ratio ◽  
Regional Recurrence ◽  
Postmastectomy Radiation ◽  
Local Regional Recurrence

PURPOSE: To define clinical and pathologic predictors of local-regional recurrence (LRR) for patients treated with neoadjuvant chemotherapy and mastectomy without radiation. PATIENTS AND METHODS: We analyzed the outcome of the 150 breast cancer cases treated on prospective institutional trials with neoadjuvant chemotherapy and mastectomy without postmastectomy radiation. Clinical stage at diagnosis was I in 1%, II in 43%, IIIA in 23%, IIIB in 25%, and IV in 7%. No patient had inflammatory breast cancer. RESULTS: The median follow-up period of surviving patients was 4.1 years. The 5- and 10-year actuarial rates of LRR were both 27%. Pretreatment factors that positively correlated with LRR were increasing T stage (P < .0001) and increasing combined clinical stage (P < .0001). Pathologic and treatment factors that positively correlated with LRR were size of the residual primary tumor (P = .0048), increasing number of involved lymph nodes (P < .0001), and no use of tamoxifen (P = .0013). The LRR rate for the 18 patients with a pathologic complete response of both the primary tumor and lymph nodes (pCR) was 19% (95% confidence interval, 6% to 48%). In a forward stepwise Cox logistic regression analysis, clinical stage IIIB or greater (hazard ratio of 4.5, P < .001), pathologic involvement of four or more lymph nodes (hazard ratio of 2.7, P = .008), and no use of tamoxifen (hazard ratio of 3.9, P = .027) independently predicted for LRR. CONCLUSION: Advanced disease at presentation and positive lymph nodes after chemotherapy predict for clinically significant rates of LRR. Achievement of pCR does not preclude the need for postmastectomy radiation if warranted by the pretreatment stage of the disease.

Distribution of Estrogen and Progesterone Receptors in Primary Tumor and Lymph Nodes in Individual Patients with Breast Cancer

1984 ◽  
Vol 70 (2) ◽  
pp. 165-168 ◽  
Author(s):  
Danila Coradini ◽  
Vera Cappelletti ◽  
Patrizia Miodini ◽  
Enrico Ronchi ◽  
Gianfranco Scavone ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Nodes ◽  
Primary Tumor ◽  
Progesterone Receptors ◽  
Cancer Tissue ◽  
Primary Tumors ◽  
Er Positive ◽  
Malignant Lymph Nodes ◽  
Negative Lymph Nodes ◽  
Primary Breast Cancer Tissue

Primary breast cancer tissue and lymph nodes were obtained from 48 patients. Estrogen receptors (ER) and progesterone receptors (PgR) were determined by a dextran-coated charcoal assay. ER were present in 72.9 % of the primary tumors and in 62.4 % of the malignant lymph nodes, whereas PgR were present in 73.0 % and 50.0 % of the cases, respectively. The primary tumor and the corresponding malignant lymph nodes showed an identical ER and PgR status, i.e., both tumor sites were receptor positive or both receptor negative in 89.6 % and 77.1 %, respectively. However, 10.4 % of the patients had ER-positive tumors but ER-negative lymph nodes and 22.9 % had PgR-positive primaries with PgR-negative lymph nodes. No receptor-positive lymph nodes showed a combination with receptor-negative primary tumor. This preliminary data shows that receptor-positive malignant lymph nodes mostly display the same receptor status as the corresponding primary tumor, whereas receptor-negative lymph nodes may have a receptor-positive primary tumor.

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