Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The survival of melanoma patients is directly related to the involvement of regional nodes and to the microscopic level of invasion of the tumor. During the past 10 years, with the increased use of aggressive surgical therapy (wide local excision or re-excision of the primary tumor and prophylactic dissection of predictably involved regional nodes) the 5-year survival rate has more than doubled. The 5-year survival has doubled in those patients with regional lymph node involvement who were infused for 5 days with L-phenylalanine mustard. Perfusion of the lower extremities with L-phenylalanine mustard has been abandoned at Vanderbilt. The potential aggressiveness of a specific melanoma can be predicted, and thus an appropriate treatment may be planned.
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PMID:Cutaneous melanoma: a twenty-year retrospective study with clinicopathologic correlation. 115 44

Melanocyte stimulating hormone (alpha-MSH, alpha-melanotropin),Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Ly-Pro-Va l-NH2, regulates melanogenesis within epidermal melanocytes of many animals. An MSH analogue ([Nle4,D-Phe7]alpha-MSH) that exhibits superpotency and prolonged biological activity has been synthesized, biologically characterized, and is presently in clinical trials to determine its possible clinical use in tanning of the skin. It also has potential for the diagnosis, localization, and chemotherapy of melanoma. The effects of this analogue on the growth, metastatic behavior, and invasive potential of a melanotic variant of Cloudman S-91 murine melanoma are reported here. In an intracutaneous murine model of melanoma cell tumor growth, the analogue did not increase primary tumor growth (size) after the period of administration of the peptide hormone analogue and did not affect spontaneous lung metastases. Survival times for the control and melanotropin-treated groups were similar, suggesting that overall tumor burden was not affected by treatment with the hormone analogue. Last, melanoma cell invasion through a human amniotic basement membrane in vitro was not enhanced compared to untreated cells.
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PMID:Effects of a melanotropic peptide on melanoma cell growth, metastasis, and invasion. 133 2

Pathologic materials were available for review from 1597 women with Stage II (positive regional node metastases) invasive breast cancer in whom estrogen receptor (ER) and progesterone receptor (PR) assays of the primary tumor were performed. These women were enrolled in a clinical trial comparing the effect of postmastectomy adjuvant L-phenylalanine mustard (L-PAM) and 5-fluorouracil (5-FU) with and without tamoxifen (NSABP Protocol No. 9). Significant pathologic and clinical associations with receptor status were similar for both ER and PR except that the latter, unlike ER, was not related to patient age. Regression analyses revealed that the most significant pathologic features related to a concordant positive ERPR receptor status was low (well differentiated) nuclear and histologic grades, slight or absent tumor lymphoid infiltrate, slight or absent necrosis and moderate or marked elastica in decreasing order of importance. All of the factors enumerated are directly or indirectly related to tumor differentiation. Recognition of four or five conforming pathologic features allows for the prediction of either ER or PR status in 70% to 80% of instances respectively, and the presence of three features in 69%. This latter figure is similar to that of estimation of nuclear grade alone. Thirty percent of ERPR estimates were discordant i.e., either ER-PR+ or ER+PR-. Pathologic features associated with discordant assays were not similar to those found when the ERPR estimates were concordant. Life table analyses revealed patients with discordant receptors to exhibit disease-free survival intermediate to that of those with ER+PR+ and ER-PR- values. This information suggests that a discordant receptor status is more reflective of an aberration of ER metabolism than a methodologic error. Histograms correlating frequency of nuclear grades with levels of ER and PR were comparable and revealed patterns indicating the propriety of relating values less than 10 fm/mg as being receptor negative. The frequency of well-differentiated nuclei increased with ascending levels of ER and PR.
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PMID:Pathologic findings from the national surgical adjuvant breast project. Correlations with concordant and discordant estrogen and progesterone receptors. 382 55

The clinical characteristics and response to therapy of a patient with meningeal sarcoma, one of four patients over a twenty-five year period at Memorial Sloan-Kettering Cancer Center, are described. The light and electron microscopic characteristics of the primary tumor and as a heterotransplant in nude mice showed minimal differences. The tumor was resistant to conventional chemotherapeutic agents, both in the patient, in vitro as a cell culture and ex vivo as a heterotransplant. Only a combination of L-phenylalanine mustard and dianhydrogalactitol produced a limited response in both the patient and the mice. This combination may have some utility in future cases.
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PMID:Human meningeal sarcoma heterotransplants in Nu/Nu mice treated with L-phenylalanine mustard (L-PAM) and dianhydrogalactitol (DAG). 384 Jun 66

High-dose methotrexate with citrovorum factor "rescue" (MTX-CF) produced an apparent complete response of the primary tumor in three patients with osteosarcoma. The response was sustained with MTX-CF, intra-arterial cis-diamminedichloroplatinum II (CDP) and Adriamycin (doxorubicin) for 18 months. Treatment was then electively discontinued. Local recurrence occurred in two patients, 6 and 4 months later, respectively. MTX-CF was reinstated and a complete response was again achieved in one patient. This has been maintained for 15+ months with MTX-CF and intra-arterial CDP administered for 13 of the 15+ months. Reinduction with MTX-CF failed in the second relapsed patient but an apparent remission was again achieved with radiation and intra-arterial CDP. This has been maintained with intravenous CDP, cyclophosphamide and phenylalanine mustard for 14+ months. A complete response in the primary tumor was still present in the nonrelapsed patient, 42 months from diagnosis. All patients have remained free of pulmonary metastases, 40+ to 42+ months from diagnosis.
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PMID:Control of primary osteosarcoma with chemotherapy. 387 85

Since 1971, 8,483 women with primary breast cancer participated in seven trials evaluating adjuvant chemotherapy. Leukemia occurred in only three of 2,068 patients treated by operation alone. The cumulative risk was 0.06% after 10 years in those free of metastases or a second primary tumor, and 0.27% in those with tumor. Thus, leukemia is not an important factor in the natural history of breast cancer. Five of 646 women receiving postoperative regional radiation developed leukemia, an overall risk of 1.39 +/- .49% at 10 years. Twenty-seven cases of leukemia (0.5%) and seven of myeloproliferative syndrome (0.1%) were recorded in 5,299 patients who received L-phenylalanine mustard (L-PAM)-containing regimens. The maximum cumulative risk of leukemia in chemotherapy recipients (leukemia of any type and myeloproliferative syndrome) was 1.68 +/- .33% at 10 years following operation. The risk excluding those with myeloproliferative syndrome was 1.29 +/- .28%. The risk of leukemia in patients free of metastases or a second primary was 1.11 +/- .30% at 10 years, and when combined with myeloproliferative syndrome, it was 1.54 +/- .36%; risks not significantly greater than observed following radiation (P = .58 and .29). No cases of leukemia were observed during the 2 years of chemotherapy and none have occurred after the seventh postoperative year. Comparisons with the surveillance, epidemiology, and end results tumor registries (SEER) data indicate an increased relative risk of acute myelogenous leukemia following postoperative regional radiation (P less than .01) and adjuvant chemotherapy (P less than .001). The findings indicate that hematologic disorders are side effects of both radiation and alkylating agents used in the adjuvant treatment of primary breast cancer. The risk of such events is lower than that reported following treatment of other solid tumors and hematologic malignancies by chemotherapy. The benefit from adjuvant chemotherapy for breast cancer exceeds the risk of leukemia. Since chemotherapy is not uniformly beneficial, efforts should be directed toward identifying responders so that only those who will benefit are exposed to the risk.
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PMID:Leukemia in breast cancer patients following adjuvant chemotherapy or postoperative radiation: the NSABP experience. 390 49

Exposure of MOPC-315 cells from the primary tumor nodule to a low concentration (0.5 nmol/ml) of melphalan (L-phenylalanine mustard; L-PAM) rendered the tumor cells capable of bringing about the generation of a potent primary antitumor cytotoxic response. Accordingly, the level of antitumor cytotoxicity generated by normal spleen cells immunized in vitro with L-PAm-treated tumor cells was at least five-fold greater than the level generated in response to untreated tumor cells. The marked superiority of L-PAM-treated tumor cells over untreated tumor cells in bringing about the generation of antitumor cytotoxicity was evident over a wide range of responder to stimulator cell ratios. The higher level of antitumor cytotoxicity exhibited by normal spleen cells immunized with L-PAM-treated tumor cells as compared with untreated tumor cells was not merely the result of direct drug-mediated tumoricidal activity, thereby reducing the number of tumor cells present which can act as cold target cell inhibitors during the 51Cr release assay. This is apparent from the observation that the level of antitumor cytotoxicity generated in response to a given percentage of stimulator tumor cells pretreated with 0.5 nmol L-PAM/ml, a drug concentration associated with retention of 60% tumor cell proliferative capacity, is substantially greater than that generated in response to less than half that percentage of untreated stimulator tumor cells. Moreover, stimulator tumor cells exposed to a fully antiproliferative concentration of L-PAM brought about the generation of a higher level of antitumor cytotoxicity than stimulator tumor cells exposed to mitomycin C at a concentration which inhibited the proliferation of the tumor cells to the same extent as the L-PAM. A low concentration of L-PAM which was effective in rendering isolated tumor cells from the primary tumor nodule capable of bringing about the generation of antitumor cytotoxicity was also effective in inducing the appearance of potent antitumor immune potential in tumor bearer splenic cells containing metastatic tumor cells.
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PMID:Melphalan-induced enhancement of tumor cell immunostimulatory capacity as a mechanism for the appearance of potent antitumor immunity in the spleen of mice bearing a large metastatic MOPC-315 tumor. 393 17

The Southwest Oncology Group in a prospective randomized study compared one year of adjuvant combination chemotherapy with continuous CMFVP (cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, and prednisone) to two years of intermittent L-phenylalanine mustard (L-PAM) in women with operable breast cancer with histologically positive axillary lymph nodes. In fully and partially evaluable patients with a 68-month median follow-up, treatment failures have occurred in 27% of 172 receiving CMFVP and 47% of 186 women given L-PAM (p = 0.002). The advantage for women receiving CMFVP was seen for all subsets regardless of menopausal status except among women who were premenopausal and had 1-3 positive nodes. Based on this study, a second study was implemented using both the estrogen-receptor (ER) content of the primary tumor and axillary nodal status to select therapy.
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PMID:Adjuvant therapy of breast cancer: the Southwest Oncology Group experience. 636 57

Between July 1975 and June 1979, 194 patients with State II or III breast carcinoma were randomized to receive either L-phenylalanine mustard (L-PAM), cyclophosphamide and 5-fluorouracil and prednisolone (CFP), or CFP and BCG. Sixty-one patients have recurred despite the adjuvant chemoimmunotherapy trial. Fifty-three are evaluable for survival and 36 for response to chemo-hormonal therapy. Those treated with a chemo-hormonal regimen for their first recurrence exhibited a 53% objective response rate to cytotoxic therapy or a 35% response to hormonal therapy. Prior exposure to L-PAM, cyclophosphamide, or 5-fluorouracil did not preclude response to "salvage" therapy regimens containing those agents. Neither menopausal status, estrogen receptor content, size of the primary tumor, adjuvant treatment, nor extent of the recurrence had any effect on subsequent survival. Overall, the entire group exhibited median survival of 37 months from initial diagnosis and 13 months from recurrence. Unlike recurrent Hodgkin's disease, there was no demonstrable relationship between the length of the disease-free interval and the likelihood of subsequent response to cytotoxic or hormonal treatment. Comparison is made to the results of "salvage" therapy administered after three other large adjuvant treatment series.
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PMID:Treatment of breast carcinoma recurrent after adjuvant chemoimmunotherapy. 638 84

Following inoculation with 1 X 10(6) MOPC-315 tumor cells, a single injection of a very low dose of melphalan (L-PAM, L-phenylalanine mustard), 0.75 mg/kg, cured most of the mice bearing a day 11 large primary tumor (20 mm) and metastases, but failed to cure mice bearing a day 4 nonpalpable tumor. Treatment of mice bearing a nonpalpable tumor with the very low dose of drug compromised the ability of the mice to respond effectively to the same low dose of drug when the tumor became large (day 12). However, a nonpalpable tumor could be eradicated by treatment of tumor bearers with a low dose of L-PAM, if it was present concomitantly with a large tumor on the contralateral side. A high dose of L-PAM, 15 mg/kg, cured mice bearing either a nonpalpable or a large tumor. The eradication of the tumor induced by the high dose of L-PAM appeared to be due solely to the tumoricidal effect of the drug. On the other hand, the eradication of the tumor by the low dose of L-PAM also required the participation of antitumor immunity of the host, since subsequent injection of antithymocyte serum abrogated the curative effect of the drug in most mice. Mice cured by a high dose of L-PAM were not resistant to subsequent lethal tumor challenge. In contrast, mice cured by the low dose of L-PAM were able to reject a tumor challenge of 300 times the minimal lethal tumor dose. The results obtained with L-PAM therapy are similar to the results that we had previously reported with cyclophosphamide therapy. Thus, the timing of therapy with a low dose of drug for mice bearing a MOPC-315 tumor is critical for successful therapy. Moreover, the selection of a low dose rather than a high dose of drug to eradicate a large tumor offers the advantage that it results in long-lasting potent antitumor immunity as a consequence of the participation of host antitumor immunity in the eradication of the tumor.
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PMID:Increase in the effectiveness of melphalan therapy with progression of MOPC-315 plasmacytoma tumor growth. 655 10


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