Showing papers by "Memorial Sloan Kettering Cancer Center published in 1981"

Malignant schwannoma--clinical characteristics, survival, and response to therapy.

Abstract: One hundred and sixty-five cases of malignant schwannoma were reviewed. Sixty-five (40%) of the patients had evidence of disseminated neurofibromatosis. Patients with neurofibromatosis were younger, had malignant schwannomas that were centrally rather than peripherally located, and had a shorter five-year survival (23%) than patients with solitary malignant schwannomas (47%). Histologically, tumors developing in patients with neurofibromatosis had a collagenous appearance, while tumors in patients without neurofibromatosis were undifferentiated and highly cellular. The clinical course of both groups of patients tended to be that of multiple local recurrences, although local recurrence had a more ominous prognosis in patients with neurofibromatosis. Chemotherapy responses in all these patients were extremely poor; however, the results of adjuvant therapy after surgery appeared encouraging. Fourteen patients (8.5%) had a malignant schwannoma in an area of prior radiation therapy and died of disease a median of 14 months after diagnosis. Malignant schwannoma should be considered in the differential diagnosis of tumors developing in areas previously treated with radiation.

Ewing's sarcoma: ten-year experience with adjuvant chemotherapy.

Abstract: Since May 1970, 67 consecutive patients with primary (nonmetastatic) Ewing's sarcoma were treated with adjuvant chemotherapy (CT) in addition to radiation therapy (RT) or surgery for the primary tumor. The first 19 patients were treated with four-drug sequential CT (T-2). The second protocol was a seven-drug induction combination CT (T-6) followed by T-2 maintenance CT; in both protocols CT was continued for 18 months. The current protocol (T-9) consists of combination CT given continuously for a period of 9 months. Of the entire group of 67 patients, 47 (70%) had axial and proximal lesions (pelvis, spine, rib, humerus, and femur) and 20 (30%) had distal lesions (forearm, leg, and foot); 53/67 (79%) are surviving free of disease 12--118 months (median 41 months) from the start of treatment. Fifteen of 23 (65%) patients with axial lesions, 19/24 (79%) patients with proximal lesions, and 19/20 (95%) patients with distal lesions are free of disease. Disease-free survivors include 28/39 (72%) male patients and 25/28 (89%) female patients. Thirty-four patients had RT, and 33 had surgery or surgery and RT, in addition to chemotherapy, for local treatment. The disease-free survival rate was 76% in the RT group and 82% in the surgery group; failure in the RT group was attributable to local recurrence in 7/34 (21%) patients. Recent experience with T-9 CT has demonstrated that CT given prior to RT or surgery can cause a great reduction in the size of the primary tumor while allowing the pathologically-eroded bone to heal prior to the initiation of RT; this also allows the high-risk patient with an axial primary (pelvis or spine) to tolerate the aggressive CT needed to prevent distant metastases. In addition to dramatically increasing survival in patients with Ewing's sarcoma, combination CT has helped achieve permanent local control. The superior survival rates for all sites of primary tumor are attributable to the early use of aggressive combination CT.

Role of two of the influenza virus core P proteins in recognizing cap 1 structures (m7GpppNm) on RNAs and in initiating viral RNA transcription.

Abstract: Purified influenza viral cores catalyze the entire process of viral RNA transcription, which includes the endonucleolytic cleavage of heterologous RNAs containing cap 1 (m(7)GpppNm) structures to generate capped primers 10-13 nucleotides long, the initiation of transcription via the incorporation of a guanosine residue onto the primers, and elongation of the viral mRNAs [Plotch, S. J., Bouloy, M., Ulmanen, L & Krug, R. M. (1980) Cell 23, 847-858]. To identify which viral core protein (nucleocapsid protein, P1, P2, or P3) recognizes the cap 1 structure on the RNA primer, we irradiated (UV) endonuclease reactions carried out by viral cores in the absence of ribonucleoside triphosphates, with a primer RNA labeled in its cap 1 structure with (32)P. The labeled cap was crosslinked to a protein that had a mobility similar to that of the P3 protein, the smaller of the two basic P proteins, in both one- and two-dimensional gel electrophoresis. This strongly suggests that this crosslinked protein is the viral P3 protein. Competition experiments with unlabeled RNAs containing or lacking a cap 1 structure established that this protein recognizes the cap 1 structure on RNAs. This protein remained associated with the cap throughout the transcription reaction, even after the viral mRNA molecules were elongated. To identify the viral core protein that catalyzes the initiation of transcription via the incorporation of a guanosine residue onto primer fragments, we irradiated transcription reactions carried out by viral cores in the presence of [alpha-(32)P]GTP as the only ribonucleoside triphosphate with an unlabeled primer RNA. A labeled guanosine residue was crosslinked to a protein that had a mobility similar to that of the P1 protein, the larger of the two basic P proteins, in both one-and two-dimensional gel electrophoresis. The transcription reaction conditions required to bring this protein in close association with a labeled guanosine residue so that crosslinking could occur indicated that this association most likely occurred coincident with the guanosine residue's being incorporated onto the primer. These results suggest that the viral P1 protein catalyzes this incorporation and hence initiates transcription.

Cutaneous T-Cell Lymphomas

Abstract: As is the case in other areas of research where advances in basic science have changed concepts in clinical medicine, it has become evident that clinical or morphological criteria alone no longer suffice to classify lymphocytic neoplasms. A definition of the subclass of the cells involved, their immunocytochemical characteristics, and their original role in the immune system appears necessary to arrive at more accurate diagnosis, prognosis, and more appropriate treatment for this group of diseases.

Patterns of narcotic drug use in a cancer pain clinic

Abstract: The treatment of pain caused by chronic disease presents several serious problems. Relief of moderate to severe pain often requires narcotic analgesics, yet physicians are often reluctant to use them because of their abuse This reluctance is further encouraged by the fact that these drugs are carefully monitored by federal and state governments and physicians in prescribing such drugs, and pharmacists in dispensing such prescriptions must follow strict regulations. In addition, the pharmacology of narcotic analgesics is poorly understood by many physicians and their patients, who believe that physical dependence and addiction are interchangeable terms. As a result, physicians generally tend to underuse narcotics in medically ill patients with severe pain 4, and this issue has recently received much public attention.6. This article reviews the limited available data on the use of narcotics in patients with chronic medical illness and our own experience in treating patients with pain due to cancer, to determine the patterns of narcotic drug usage.

Identification of leukemia-associated inhibitory activity as acidic isoferritins. A regulatory role for acidic isoferritins in the production of granulocytes and macrophages.

Abstract: Acidic isoferritins have been identified as leukemia-associated inhibitory activity (LIA), which suppresses colony and cluster formation of colony-forming unit-granulocyte macrophages from normal donors but not from patients with leukemia. LIA was detected in all ferritin preparations tested, including ferritin isolated from normal heart, spleen, liver, and placental tissues, and from the spleens of patients with chronic myelogenous leukemia and Hodgkin's disease. Purified preparations of LIA were composed almost entirely of acidic isoferritins, as determined by immunoassay, radioimmunoassay, and isoelectric focusing. The inhibitory activity in the LIA and ferritin samples was inactivated by a battery of antisera specific for ferritin, including those prepared against acidic isoferritins from normal heart and spleen tissues from patients with Hodgkin's disease, and those previously absorbed with basic isoferritins. Antisera absorbed with acidic isoferritins did not inactivate the inhibitory activity. Separation of LIA and chronic myelogenous leukemia and normal spleen ferritin by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and isoelectric focusing confirmed that the regions of peak inhibitory activity corresponded in each to an apparent molecular weight of approximately 550,000 and to a pI value of 4.7. Similar physicochemical characteristics included inactivation by methods that dissociate ferritin molecules into subunits and by treatment with trypsin, chymotrypsin, pronase, and periodate. The purified preparations were extremely stable to heat treatment. The glycoprotein nature of the inhibitory activity was substantiated because it bound to concanavalin A-Sepharose and was eluted off by alpha-methyl mannose. Inhibitory activity of the activity of the acidic isoferritins was detected at concentrations as low as 10(-17)-10(-19) M and iron saturation did not appear to be necessary for its action. These results implicate acidic isoferritins in the regulation of normal myelopoiesis and suggest a role for them in the progression of leukemia.

The continuing challenge of retroperitoneal sarcomas

Abstract: Treatment of 158 patients with retroperitoneal sarcomas (1951--1977) resulted in a mean five-year survival of 40% (range 37--45%) after complete excision. Only 22% (range 19--25%) of the patients were free of disease. Survival for five years after incomplete excision was 3%. Operative mortality after complete excision declined from 21 to 2% during this period. Anatomical barriers to wide resection, high-grade histology, and local recurrence were the most important factors determining survival. The need for adjuvant therapy is emphasized by a 77% recurrence rate among patients with apparent complete excision. Brachytherapy (125Iodine, 192Iridium) afterloading techniques and supplemental external radiation are recommended to improve local control and chemotherapy is indicated to diminish the potential for metastatic spread. The contribution of adjuvant therapy after complete excision in this series was difficult to assess because of the number of uncontrolled variables, different histologic types, and limited number of patients treated by multimodality therapy. Although radiation and chemotherapy may be beneficial after incomplete resection, prolonged survival was only seen in patients with liposarcoma and low-grade fibrosarcoma.

Flow cytometry of breast carcinoma: I. Relation of DNA ploidy level to histology and estrogen receptor

Abstract: Flow cytometry studies of the DNA distribution of tumor cells from 92 human breast cancers showed measurable aneuploidy (hyperploidy) in 83 cases (92%). The DNA ploidy values were unimodal in each case, but there was a bimodal distribution for the entire series. One group of tumors had a diploid or near diploid DNA distribution and a second group had ploidy levels from triploid to tetraploid or higher. The tumors with lower DNA ploidy (at or near diploid) tended to be histologically low grade, cytologically more orderly and estrogen-binding positive; those with higher DNA ploidy were more likely to be higher grade, more anaplastic, and estrogen-binding negative.

Mandibular “swing” approach for oral and oropharyngeal tumors

Abstract: This study reviews the history, indications, and operative technique for median mandibulotomy with paralingual extension (mandibular "swing"). A 21-year experience is presented, during which this operative approach was used in 49 patients with tongue cancer and 16 others with oropharyngeal lesions. Mandibular "swing" appears to offer more versatility and fewer problems than either median labiomandibular glossotomy or lateral mandibulotomy. Good local control can be anticipated in properly selected patients because the tumor exposure is comparable to that achieved in operations involving jaw resection.

Priming of influenza viral RNA transcription by capped heterologous RNAs.

Abstract: Influenza virus is a negative-stranded RNA virus, i.e., the viral messenger RNA (mRNA) is complementary to the genome RNA (which is segmented), and the virion contains the enzyme system which transcribes the genome RNA into the viral mRNA. This virus employs a unique mechanism for the initiation of the synthesis of its mRNA. Specifically, the virion-associated transcriptase system needs to cannibalize capped heterologous RNAs, i.e., eukaryotic cellular mRNAs and/or their precursors, in order to synthesize the viral mRNA. This process involves the clipping off by a virion-associated endonuclease of a small piece of the eukaryotic mRNA near its 5’-end, followed by the utilization of this RNA fragment as a primer to initiate the synthesis of the viral mRNA. The methylated cap structure (m7GpppNm, where Nm = 2’ -O-methylated nucleoside) found at the 5J -end of all mammalian cellular mRNAs is part of the RNA fragment that is used as primer and transferred from the cellular to the viral mRNA, and this cap structure is absolutely necessary for the viral nuclease and the priming reaction. In fact, the 5;-methylated cap structure is more stringently required for priming influenza viral mRNA synthesis than for the process in which it had previously been shown to play a role, the translation of mRNAs in cell-free systems. This mechanism for viral mRNA synthesis explains why influenza virus requires the functioning of the host-cell nuclear RNA polymerase II in order to replicate: newly synthesized host mRNAs and/or their precursors are needed as primers for viral mRNA synthesis.

Estrogen receptor protein of breast cancer as a predictor of recurrence

Abstract: To assess the value of estrogen receptor protein (ERP) as a predictor of tumor recurrence, 556 patients treated by mastectomy between 1973 and 1978 for primary operable breast cancer had ERP determination of their tumors. All patients had histologically negative nodes. Two hundred fifty-six patients were ERP-positive, 233 were ERP-negative, and 67 were ERP-borderline. ERP-borderline patients showed recurrence and survival figures similar to ERP-negative patients and were grouped with them in the analysis. With a median follow-up of 75 months, overall survival for the entire group at 72 months was 93% with a disease-free survival of 85%. No difference in either overall survival or DFS was noted between the ERP-positive (94% and 83%, respectively) and ERP-negative (91% and 86%, respectively) groups. The incidence of recurrence in premenopausal women was 12% (14/115) in the ERP-negative patients versus 17% (9/48) among the ERP-positive patients. This contradicts the current impression that ERP-negative, premenopausal patients have a poorer prognosis than ERP-positive patients. Postmenopausal patients had a 16% recurrence in both ERP-negative (27/171) and ERP-positive (31/202) categories. On the basis of 6-year median follow-up, it was concluded that ERP status is not an indicator of recurrence. In particular, patients with negative nodes should not be considered for adjuvant chemotherapy on the basis of negative estrogen receptor status of their primary tumors.

Distinct lung-colonizing and lung-metastasizing cell populations in B16 mouse melanoma.

Abstract: Establishment of distant metastases by solid tumours requires that some tumour cells separate from the primary growth, infiltrate surrounding normal tissues, invade blood vessels or lymphatic channels, and extravasate into microenvironments favourable for proliferation1. It is probable that only a small subpopulation of tumour cells is endowed with these special attributes2. The biological properties of potentially metastatic tumour cells are being investigated extensively by means of an ‘experimental metastasis’ assay, in which cultured cells are introduced directly into blood vessels and, several weeks later, organs examined for tumour growths1–8. Although this assay allows controlled and quantitative experimentation, the suitability of experimental metastasis (colonization) as a valid representation of true metastasis is uncertain. I report here that organ colonization after injection of cells directly into the blood vasculature is not necessarily predictive of spontaneous metastatic potential from subcutaneous transplants. Indeed, some cell lines derived from the B16 mouse melanoma produce numerous lung colonies when injected intravenously (i.v.) but rarely metastasize, whereas others are spontaneously metastatic to the lungs but produce few lung colonies after i.v. injection. These differences in behaviour are evident only when the possibility of colonization occurring due to accidental introduction of melanoma cells into blood vessels is excluded.

Hyperfractionated total body irradiation for bone marrow transplantation: I. early results in leukemia patients☆☆☆

Abstract: Bone marrow transplantation following cytoreduction with total body irradiation and cyclopbospbamide has previously been shown to be of value in treating refractory leukemias. Major problems, however, have been fatal interstitial pneumonitis and leukmmac relapse. In an attempt to minimize these problems, we initiated a new hyperfractionsted regimen for total body irradiation, with partial long sparing. From May, 1979 throughJuly, 1980, we treated 48 leukemia patients according to this regimen, varying in age from 1.5 to 42 years old (mead age: 18 y). Analysis in September, 1980, with follow-up from 2–16 mos, showed that we have a significantly reduced incidence of interstitial pneumonitis compared with single dose (1000 rad) irradiation (33 vs 70%), as well as decreased deaths attributable to interstitial pneumonitis (23 vs 50%). This is reflected in the survival curves, with loss of the early drop in survival previously observed with single dose irradiation. One year actuarial survival was 65% for acute lympbocytic leukemia (n - 16) and 72% for acute non-lymphocytic leukemia (n - 29). This compares with only 17% for acute non-lympbocytic leukemia patients (n = 12) on our previous single dose regimen. Age was: also found to be an important parameter for both survival and interstitial pneumonitis.

CEA (carcinoembryonic antigen): Its role as a marker in the management of cancer

Abstract: A consensus Development Conference was held at the National Institutes of Health from September 29-October 1, 1980, to address issues concerning the role of carcinoembryonic antigen (CEA) as a marker in the management of cancer. The panel met following formal presentations and discussions to assess the issues based on the evidence presented. These issues included: Should CEA be used in cancer screening? Is CEA helpful in cancer diagnosis? What does CEA tell about the extent and outcome of cancer? Is CEA helpful in monitoring cancer treatment? This paper constitutes the panel's findings.

The incidence and extent of pelvic lymph node metastases in apparently localized prostatic cancer.

Abstract: Pelvic lymphadenectomy was performed in 300 patients with apparently localized adenocarcinoma of the prostate. Pelvic lymph node metastases were identified in 119 patients (40%) and in 35 of these cases (29%) the metastases involved a solitary lymph node. The incidences of metastases for clinical stage B1, B2 and C tumors were 7, 43, and 60%, respectively. The extent of the metastases in terms of the number and distribution of the involved nodes correlated directly with the clinical stage of the primary tumor. The incidences of metastases associated with well-differentiated, moderately differentiated and poorly differentiated tumors were 27, 45, and 70%, respectively. The degree of tumor differentiation, however, had no apparent impact on the incidence of metastases among patients with clinical stage B1 and C neoplasms. Since tumor stage, tumor grade, and pelvic lymph node metastases have each been demonstrated to be of prognostic significance in prostatic cancer, the status of the pelvic lymph nodes should not be considered an isolated prognostic parameter in patients with otherwise localized prostatic cancer.

The seventies evolution in liver surgery for cancer.

Abstract: During the past decade, one of the major changes in the field of oncology has been in the surgical approach to primary and secondary cancer of the liver. As a result of data and experience gained in liver transplantation programs and with the application of vascular surgical principles, resectability rates have been increased. The present rate of 32% has been achieved with an overall 30-day operative mortality rate of 9%. More sophisticated intraoperative and postoperative supports have been essential in achieving these results. The median operating time is now 4 3/4 hours in length. Complications are minimal. The median postoperative hospital stay is now 13 days. During the past decade, 436 patients with liver tumors were treated by the authors. It has become apparent in this experience and in that reported by others that an increasing number of patients with primary liver cancer or metastatic cancer in the liver can be cured by surgery with minimal operative risk. Adjuvant chemotherapy may increase the salvage rate. Current therapeutic results are best evaluated after staging of the liver disease: Stage I (no involvement of margins of resection, hepatic vascular structures or bile ducts; all gross disease removed): 85% three-year survival estimate, using the Kaplan-Meier method, for individuals with primary liver cancer; 71% for those with metastatic colorectal cancer. Stages II and III (regional or extrahepatic spread): 22% three-year survival for individuals with primary liver cancer but no survivors at two years with metastatic colorectal cancer. These data permit better selection of patients who are most likely to benefit from surgery.

Canine Hepatocellular Carcinoma

Abstract: In a study of 110 primary hepatic neoplasms in dogs, 55 hepatocellular carcinomas and two combined hepatocellular and cholangiocarcinomas were diagnosed. These neoplasms were classified into the following 11 groups based on histo-architectural pattern: trabecular, peliod, cobblestone, peritheliomatous, anaplastic, pseudoglandular, pleomorphic, scirrhous, clear cell, solid, and combined hepatocellular and cholangiocarcinoma. The neoplastic hepatocytes varied from almost normal to highly anaplastic spindle cells. Pleomorphic and giant cells were common in some groups, rare or absent in others. Metastasis was found in 61% (35 of 57), in contrast to a much higher percent in man, indicating the possibility of a different pathogenesis in the dog.