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Biomedical subjects

S D Nathanson

Publications and source records attributed to S D Nathanson.

At least 37 records · Page 2Linked to original sources

Lymph flow from murine footpad tumors before and after sublethal hyperthermia.

The effect of local hyperthermia (43.5 degrees C for 1 h) on lymph flow from B16-F10 tumor-bearing foot pads of C57BL/6 mice was measured by monitoring the clearance of 99mTc-labeled human serum albumin. The foot was represented by a single-compartment model enabling a quantitative computation of lymphatic flow from the tumor to regional lymph nodes. Lymphatic flow from untreated tumors was 0.0059 +/- 0.0011 ml/min cm3 compared to 0.0118 +/- 0.0027 ml/min cm3 lymphatic flow from tumors immediately following heating. Morphological alterations in tumor blood vessels result in their high vascular permeability. The increase in lymphatic clearance from tumors after sublethal hyperthermia is compatible with the increase in interstitial fluid formation in tumors based on Starling's Law.

Animals↗

Use of polypropylene mesh to stabilize the "floating humerus" after total scapulectomy.

Total scapulectomy for malignant disease is a rarely performed procedure that presents a significant challenge for shoulder reconstruction. Failure to stabilize the resulting "floating humerus" may result in significant esthetic and functional problems. Current techniques of reconstruction and stabilization may yield suboptimal results and significant morbidity. We report a case of Ewing's sarcoma of the scapula, which required total scapulectomy. Polypropylene mesh was used in an attempt to prevent migration of the head of the humerus. The result was a stable shoulder with satisfactory motion and no additional morbidity. We believe that polypropylene mesh offers an advantage in shoulder reconstruction after total scapulectomy and should be considered as an option for stabilization of the humerus.

Adult↗

Changes associated with metastasis in B16-F1 melanoma cells surviving heat.

Metastasis to distant sites is mediated by various receptors on the surface of tumor cells. B16-F1 melanomas surviving 43.5 degrees C heat in vitro for 15 minutes and cultured for 10 days bind significantly increased amounts of the basement membrane protein laminin. Motility of heat-resistant B16-F1 cells in vitro toward the chemoattractant laminin is significantly increased. The increased expression of putative laminin receptors may be associated with increased metastasis of melanomas after subcurative hyperthermia.

Cell Survival↗

Relationship of spontaneous regional lymph node metastases to dose of local irradiation of primary B16 melanomas.

We evaluated the effects of local X-irradiation on microscopic or small macroscopic primary melanomas in the feet of C57BL/6 mice and the subsequent development of spontaneous femoral lymph node (LN) metastases. Doses of 30, 40, 55, 62.5, or 72.5 Gy often cured the foot tumor and metastases to regional femoral lymph nodes were relatively uncommon. Doses of 3.75, 7.5, 10, 15, and 20 Gy were associated with a dose-dependent regrowth delay of the foot tumor treated at microscopic size. Foot melanomas that were not cured spread to regional femoral LNs more frequently (P less than 0.001). The relative risk of developing femoral LN metastasis increased 2.55 times for each 1-mm increase in the anteroposterior diameter of the primary foot tumor in mice with 20 days of primary tumor exposure and increased 4.87 times for each 1-mm increase in mice with 100 days of primary tumor exposure. Although tumors treated with subcurative doses of irradiation had a longer period of time to metastasize to regional LNs for each 1-mm increase in primary tumor size, this variable alone did not account for the increased incidence of metastasis seen with irradiation.

Animals↗

Lung metastases after curative or noncurative irradiation of microscopic primary melanomas.

Melanomas growing in the feet of syngeneic C57BL/6 mice were treated with a single dose of X-irradiation. After doses of 0, 3.75, 7.5, 10, 20, or 30 Gy the tumor-bearing limb was amputated at tumor sizes 1, 2, 3, 4, or 5 mm. After doses of 40, 50, 62.5, or 72.5 Gy, progressive tumor growth did not occur, and amputation of tumor-bearing limbs was done when controls were 1, 2, 3, 4, or 5 mm in size. Eighteen days after amputation the mice were killed, and pulmonary metastases were documented at autopsy. None of the mice developed pulmonary metastases after curative irradiation of the primary foot tumor. After subcurative irradiation there was a significant increase (P less than .003) in pulmonary metastases. The size of the primary melanoma is important in the prediction of these metastases. In this model melanomas can be cured by an adequate dose of irradiation, but in those not cured the incidence of lung metastases is increased. The impact of this biologic phenomenon on survival is unclear.

Animals↗

Organ-specific chemotactic factors present in lung extracellular matrix.

The preferential colonization of a distant organ by a circulating tumor cell (organ specific metastasis) may be regulated by chemotactic factors present within the extracellular matrix of the host organ. Organ-specific extracellular matrix was prepared from murine kidney and lung by high salt extraction and DNAase/RNAase digestion. A soluble protein fraction (S2) from each of the matricies was obtained by 4 M guanidine extraction and was tested for organ-specific chemotactic activity in a modified Boyden chamber. The lung colonizing B16-F10 and B16-BL6 tumor cell lines demonstrated organ-specific motility only toward the lung extract. The low metastasizing B16 parental line and liver colonizing B16-L4b line showed no preference for either lung or kidney. The lung activity resolves into five fractions by gel filtration chromatography, with the highest activity eluting at Mr approximately 71,000. Chemotactic factors present in lung extracellular matrix may regulate the preferential colonization of an organ by stimulating the migration of tumor cells in a specific manner. These factors may be released during the degradation of the extracellular matrix.

Cell Line↗

Primary malignant giant cell tumor of bone: "dedifferentiated" giant cell tumor.

Well documented examples of primary malignant giant cell tumor of bone (giant cell tumor and concurrent sarcoma arising de novo) are exceedingly rare in the literature. We report a case arising in the left ischium of a 44-yr-old man. He had no previous history of radiation therapy or multiple resections. Histologically, the tumor was a typical giant cell tumor of bone juxtaposed to a malignant fibrous histiocytoma (MFH). The juxtaposition of a high grade sarcoma (MFH) and a locally aggressive nonmalignant neoplasm such as giant cell tumor is analogous to several other tumors of bone and soft tissue in which a low grade malignant or locally aggressive tumor can be associated with MFH or fibrosarcoma de novo, namely chondrosarcoma, chordoma, liposarcoma, and well differentiated intraosseous and parosteal osteosarcoma. The presence of a high grade malignant component in each of the aforementioned neoplasms generally portends a more ominous prognosis, although this is not invariably true. Recognition of the phenomenon of "dedifferentiation" (or tumor progression) in some bone tumors and sarcomas is important to ensure appropriate treatment. Distinction from secondary malignant giant cell tumors which are usually radiation induced is also important, since the latter have a much worse prognosis than those with dedifferentiation occurring de novo.

Adult↗

Regional lymph node and pulmonary metastases after local hyperthermia of melanomas in C57BL/6 mice.

The effects of local tumor hyperthermia on regional lymph node metastases are inconclusive. We studied the effects of hyperthermia on the incidence of popliteal, femoral, and abdominal lymph node metastases in C57BL/6 mice with primary B16 melanomas (F10 variant) growing subcutaneously in the left foot. Tumors were heated to 42.3, 43.5, and 44.2 degrees C for 90 minutes either 7 days after inoculation of 5 X 10(4) viable cells (microscopic tumor = mic) or when the tumors were approximately 3 mm in diameter (macroscopic tumor = mac). Femoral lymph node metastases occurred in 0/21 control animals and in 8/22 (36%), 11/19 (58%), and 11/17 (65%) animals whose primary tumors were heated to 42.3, 43.5, and 44.2 degrees C, respectively. For all three treatments, the increase in metastases as compared to controls was statistically significant (p less than 0.004, Fisher's exact test). The incidence of abdominal lymph node metastasis was slightly higher in the treated groups than controls. Twenty of 21 (95%) control mice developed popliteal lymph node metastases and hyperthermia-induced increases could not be demonstrated. Fifteen of 21 control mice killed 3 weeks after amputation of tumor-containing leg had pulmonary metastases with an average of 6 +/- 4 (standard deviation) lesions per affected mouse. Pulmonary metastases occurred in 22/22 (100%), 17/19 (89%), and 13/17 (76%) of mice whose tumors were heated to 42.3, 43.5, and 44.2 degrees C, respectively. The numbers of metastases for affected mice were significantly increased compared to controls for tumors heated to 43.5 and 44.2 degrees C (28 +/- 43, 43 +/- 52, 119 +/- 121, p greater than 0.02, p less than 0.006, p less than 0.002, for two sample T-test). While 0/8 mic tumors were cured 5/9 mac tumors heated to 44.2 degrees C disappeared (p less than 0.03, Fisher's exact test) and there was a growth delay in the remaining mice. Mic tumors, heated to 43.5 degrees C, had an accelerated onset of growth while mac tumors heated to this temperature had a slight growth delay. Growth of both mic and mac primary tumors heated to 42.3 degrees C was similar to controls. These results show that therapeutic and subtherapeutic local hyperthermia increases metastases to regional lymph nodes and to lungs even when primary tumor growth rate is partially or totally controlled.

Animals↗

An anatomic approach to tumors of the psoas major muscle.

The technique of excision of the entire psoas major muscle via the retroperitoneal route is described. This approach prevents direct seeding of the peritoneal cavity with tumor cells and provides relatively easy access to the entire psoas major muscle and its blood supply. The anatomic characteristics of the retroperitoneal space preclude wide surgical margins in whatever approach is used, and in this regard the retroperitoneal approach is probably no more difficult than the transperitoneal approach. The relative ease with which a primary tumor in the psoas major muscle can be excised makes the retroperitoneal approach desirable from the surgeon's point of view.

Back↗

Spontaneous regional lymph node metastases of three variants of the B16 melanoma: relationship to primary tumor size and pulmonary metastases.

We studied the patterns of spontaneous regional lymph node metastases of three variants (F1, F10, and BL6) of the B16 melanoma in C57BL/6 mice and related the incidence to primary tumor size and pulmonary metastases. The incidence of regional lymph node and pulmonary metastases correlated with increasing primary tumor size (p less than or equal to 0.0001). The incidence of pulmonary metastases in mice whose regional lymph nodes did not contain tumor also correlated with increasing primary tumor size (p less than or equal to 0.0001). This propensity for direct hematogenous spread was more apparent in BL6 tumors than in F1 and F10 tumors (p less than or equal to 0.0001). BL6 tumors also metastasized to regional nodes at smaller primary tumor sizes (p less than or equal to 0.04). Heterogeneous variants that metastasize earlier to regional lymphatic and hematogenous sites dictates the natural history of the primary tumor. Whether prophylactic lymphadenectomy for melanomas is therapeutic may depend on dissemination-related phenotypic characteristics.

Animals↗

Carcinomas of the colon and rectum. A comparison of staging classifications.

Five staging methods for colorectal cancer were compared to the Dukes method in order to assess which methods were most sensitive and specific. Three hundred fifty-two patients with resected carcinomas of the colon and rectum were followed from 6 to 11 years or until death. All patients were staged by intraoperative and pathological criteria. Survival curves were constructed for each stage. The pTNM system was most sensitive at predicting death. The Gastrointestinal Tumor Study Group (GITSG) system was the most specific at predicting survival. However, the Dukes system did no worse than either of these staging systems and predicted relatively few false-positive and false-negative cases. The sensitivity and correctness of the Dukes system was improved by adding information regarding percent of lymph node metastases, ulceration of the primary tumor, and adjacent organ invasion.

Adenocarcinoma↗

Perioperative allogeneic blood transfusions. Survival in patients with resected carcinomas of the colon and rectum.

Blood transfusion (BT) is reported to cause immunosuppression. We postulated that BT might therefore adversely affect the prognosis of carcinomas of the colon and rectum. We analyzed the overall and recurrence-free survival of 366 patients whose colorectal carcinomas were resected. The 199 patients who received perioperative BTs appeared to survive less well than the 167 patients who received no blood products. However, Cox analysis, which adjusts for other prognostic variables, shows that the difference was not statistically significant. Although 43% of transfused patients survived, as compared with 56.5% of nontransfused patients, this difference was due to variables other than transfusion. This study did not support the hypothesis that BT has an adverse effect on survival of patients with colorectal cancer.

Adenocarcinoma↗

Prophylactic lymphadenectomy for B16 melanoma in C57/BL6 mice: survival based on size and heterogeneous variant of the primary.

Survival following prophylactic lymphadenectomy by hip disarticulation in mice with three B16 melanoma variants was studied. C57/BL6 mice inoculated with viable tumor cells (F1, F10, and BL6) into the left hind foot pad were randomized to wide excision (WE) of the primary tumor alone or wide excision plus prophylactic lymphadenectomy (WE plus PL) at 1-, 2-, 3-, 4-, and 5-mm primary tumor sizes (each group, N = 6). Overall survival time was improved by WE plus PL. A significant survival advantage and cure was apparent for the F1 and F10 variants with primary tumor sizes of 2 and 3 mm (F1, 2 and 3 mm, P less than 0.001; F10, 2 mm, P less than 0.006; 3 mm, P less than 0.001), but not for the BL6 variant. Prophylactic lymphadenectomy provides a therapeutic advantage in mouse melanomas of intermediate size in two of the three variants of B16.

Animals↗

Kinetics of the MLR response following single donor-specific allogeneic blood transfusions.

Prior blood transfusion (BT) confers a significant improvement in transplant survival in recipients (1). However, increased survival across major histocompatibility barriers generally requires the administration of immunosuppressive agents (2-5). The mechanisms by which BT prolongs graft survival have not been fully elucidated. Experimental evidence suggests that suppressor cells (6,7), soluble suppressor factors (8), and blocking antibodies (9) may play a role.

Animals↗

Factors prognostic for survival in patients with malignant melanoma spread to the regional lymph nodes.

To establish clinical and histologic determinants of survival, records of all UCLA patients with resectable melanoma metastatic to the lymph nodes during the years 1954-1976 were reviewed. These 150 patients were treated first with wide excision, lymphadenectomy, and with radiation/chemotherapy and/or additional surgery only if further recurrences developed. None received adjuvant immunotherapy or chemotherapy. In 97 of 139 patients with identified primary tumors, slides of the primary lesion were reviewed. Putative prognostic factors included age, sex, parity, site of primary tumor, presence of satellitosis, clinical status of nodes, histologic characteristics of primary lesion (Clark's level, thickness of tumor, presence/width of ulceration, and number of mitoses/HPF), time from biopsy of primary tumor to lymphadenectomy, and number of positive nodes. kaplan-Meier estimates of survival for the entire group at one, two, five, and ten years were 73, 55, 37, and 33%, respectively. Median follow-up period of survivors was four years. Univariate analyses using the log-rank test showed that thickness of the primary lesion (p less than 0.001), width of ulceration (p = 0.003), absence of ulceration (p = 0.024), and number of positive nodes (p = 0,.033) were prognostic for survival. In multivariate analysis by the Cox procedure, thickness of the primary (p = 0.001) and number of melanoma-containing nodes (p = 0.043) were prognostic for survival. Location of the primary tumor became marginally significant (p = 0.12) in the multrivariate model. These findings demonstrate the prognostic importance of characteristics of both the primary lesion and extent of regional dissemination. Future prospective randomized trials for (adjuvant) therapy of Stage II melanoma should be stratified by these variables.

Adolescent↗