Asc-Seurat: analytical single-cell Seurat-based web application.

BACKGROUND: Single-cell RNA sequencing (scRNA-seq) has revolutionized the study of transcriptomes, arising as a powerful tool for discovering and characterizing cell types and their developmental trajectories. However, scRNA-seq analysis is complex, requiring a continuous, iterative process to refine the data and uncover relevant biological information. A diversity of tools has been developed to address the multiple aspects of scRNA-seq data analysis. However, an easy-to-use web application capable of conducting all critical steps of scRNA-seq data analysis is still lacking. We present Asc-Seurat, a feature-rich workbench, providing an user-friendly and easy-to-install web application encapsulating tools for an all-encompassing and fluid scRNA-seq data analysis. Asc-Seurat implements functions from the Seurat package for quality control, clustering, and genes differential expression. In addition, Asc-Seurat provides a pseudotime module containing dozens of models for the trajectory inference and a functional annotation module that allows recovering gene annotation and detecting gene ontology enriched terms. We showcase Asc-Seurat's capabilities by analyzing a peripheral blood mononuclear cell dataset. CONCLUSIONS: Asc-Seurat is a comprehensive workbench providing an accessible graphical interface for scRNA-seq analysis by biologists. Asc-Seurat significantly reduces the time and effort required to analyze and interpret the information in scRNA-seq datasets.

Immunological effects of flavone acetic acid.

Flavone acetic acid (FAA) enhances natural killer and lymphokine-activated killer (LAK) cell activity in mice. We examined the immunological effects of FAA on human blood cells both in vivo and in vitro. Peripheral blood natural killer and LAK activity and lymphocyte subsets were evaluated in cancer patients after receiving 3-h infusion of FAA at either 8.5 or 10 g/m2 with alkalinization. Natural killer cell activity and the number of Leu-19 (CD56) positive cells decreased at 24 h after infusion; significant changes in LAK activity and the number of Leu-1 (CD5), Leu-3 (CD4), Leu-2 (CD8) cells were not observed. Peripheral blood mononuclear cells and peripheral blood lymphocytes collected from healthy volunteers were exposed in vitro to FAA, interleukin 2, and FAA plus interleukin 2. FAA, alone or in combination, failed to enhance LAK activity at any time point or concentration from peripheral blood mononuclear cells and peripheral blood lymphocytes. Concentrations of greater than or equal to 100 micrograms/ml antagonized the generation of LAK activity from interleukin 2 treated peripheral blood lymphocytes. These data suggest that FAA may not be useful in enhancing immunological responses in humans.

Prevention of mammary tumors with a chimeric HER-2 B-cell epitope peptide vaccine.

Synthetic peptide vaccines targeting B-cell epitopes of the extracellular domain of the HER-2 oncoprotein were evaluated for their capacity to elicit HER-2-specific antibodies with antiproliferative activity. Several HER-2 B-cell epitopes were identified by computer-aided analysis of protein antigenicity, and selected B-cell epitopes were synthesized colinearly with a promiscuous T-helper epitope (208-302) derived from the measles virus fusion protein at either the NH2 or COOH terminus linked via a four-residue turn sequence (GPSL). In addition, one epitope sequence, 628-647, was mutated to optimize disulfide pairing to mimic the native HER-2 receptor. All of the four selected epitopes elicited high-titered antibodies in outbred rabbits with exceptionally high titers for MVF-HER-2(628-647). These antibodies were cross-reactive with the native HER-2 receptor. Antibodies elicited by MVF HER-2(628-647) inhibited proliferation of human HER-2-overexpressing breast cancer cells in vitro and caused their antibody-dependent cell-mediated cytotoxicity. Furthermore, immunization with MVF-HER-2(628-647) prevented the spontaneous development of HER-2/neu-overexpressing mammary tumors in 83% of transgenic mice. The engineered, chimeric peptide B-cell immunogen MVF-HER-2(628-647) may have applications in the prevention of HER-2-overexpressing cancers.

Gastrointestinal involvement and multiple lymphomatous polyposis in mantle-zone lymphoma.

The clinical, histologic, and immunologic features of three cases of lymphoma presenting with gastrointestinal symptoms and involving the gastrointestinal tract were studied. Two of the cases had involvement of long segments of the bowel with polypoid lesions, a rare presentation of gastrointestinal lymphoma referred to as multiple lymphomatous polyposis (MLP). All cases were classified as mantle-zone lymphoma (MZL), a follicular variant of intermediate lymphocytic lymphoma (ILL) characterized by the proliferation of small atypical lymphoid cells as wide mantles surrounding benign-appearing germinal centers. The patients were typical of other patients with MZL in that they were male, middle age or older, and their clinical courses were not aggressive despite the presence of disease at an advanced stage. Our review of the literature suggests that there is an inordinate number of cases of MZL with gastrointestinal involvement. We also note that most reports of cases of MLP have described histologic lesions remarkably similar to what we have observed. We conclude that MZL may have predilection for involvement of the gastrointestinal tract, that this involvement is often in the manner of MLP, and that most cases of MLP probably have MZL or ILL.

Phase II trial of interferon-beta-serine in metastatic renal cell carcinoma.

Interferon-beta-serine (IFN-beta-ser) is a muteine, recombinant IFN that is tolerated at a dose fivefold to 10-fold higher than IFN-alfa and interacts with the same cell membrane receptor as IFN-alfa. We hypothesized that at high doses IFN-beta-ser might induce a higher response rate than IFN-alfa in metastatic renal cell carcinoma. We undertook a phase II trial of IFN-beta-ser in patients with metastatic renal cell carcinoma. Patients were treated three times each week by a 2-hour intravenous infusion. Doses were escalated weekly (.25 to 5.5 mg, 1 mg = 180,000,000 U) until the maximum-tolerated treatment dose (MTTD) was determined. The MTTD is defined as one dose level less than that which caused grade 3 toxicity and was subsequently administered three times weekly for at least 4 weeks. Twenty-nine patients were entered, and 25 were assessable for response and toxicity. The performance status was 0-1 in all patients and only one patient received previous chemotherapy. The MTTD dose was 2.5 mg (range, 0.5 to 5.5 mg per treatment), although in 10 patients, doses were later deescalated because of cumulative toxicity. Initial dose-limiting toxicity and cumulative toxicity were fatigue, malaise, and fever in most patients. Hepatic transaminitis, neutropenia, and elevation of serum creatinine were also observed but were not dose-limiting. There was one complete response (CR) and four partial responses (PRs). All responses but one occurred in pulmonary metastases. The median time to response was 26 days (range, 17 to 102 days). These data demonstrate that IFN-beta-ser given in high doses exhibits significant antitumor activity in renal cell carcinoma; however, the objective response rate is 20%. This is no higher than previous IFN studies; therefore, we reject the hypothesis than IFN-beta-ser at high doses may induce a greater response rate than IFN-alfa. However, we did observe more responses than were seen in a similar trial undertaken with lower dose IFN-beta serine in renal cell carcinoma.

Phase I trial of escalating doses of interleukin-1 beta in combination with a fixed dose of interleukin-2.

PURPOSE: Interleukin-1 (IL-1) and IL-2 have synergistic antitumor and myelostimulatory activities. We investigated the clinical and biologic effects of IL-1/IL-2 therapy. PATIENTS AND METHODS: Twenty patients with metastatic cancer, divided into five cohorts, were treated with escalating doses of IL-1 beta (0.005 to 0.2 micrograms/kg/d) administered as a 30-minute intravenous (IV) infusion on days 1 to 4, combined with a fixed dose of IL-2 (0.1 mg/m2/d) administered by continuous IV infusion on days 1 to 4. The 4-day cycles were repeated weekly for up to 8 weeks in the absence of toxicity and/or progressive disease. RESULTS: Patients tolerated up to 0.2 microgram/kg/d of IL-1 beta in combination with IL-2 without severe adverse effects. Peripheral-blood CD4-to-CD8 ratios and lymphokine-activated killer (LAK) activity were higher at the lower doses (0.005 to 0.05 microgram/kg/d) of IL-1 beta and higher than that of a cohort of patients treated with IL-2 alone. WBC counts, primarily neutrophils, increased significantly with higher doses of IL-1 beta (0.1 to 0.2 microgram/kg/d). Platelet counts were not significantly altered. Increases in serum IL-6, interferon gamma (IFN-gamma), and soluble IL-2 receptor levels were observed, but did not vary with IL-1 beta dose. Tumor regressions were observed in patients with colorectal cancer, melanoma, and renal cell carcinoma. CONCLUSION: IL-1 beta cancer be administered in combination with IL-2 with acceptable toxicity. Our results suggest that the addition of even low-dose IL-1 beta to IL-2 may be associated with potentially beneficial biologic activity; higher doses of IL-1 beta (0.1 to 0.2 microgram/kg/d) may add potentially beneficial hematologic activity.

Randomized comparison of cisplatin plus fluorouracil and carboplatin plus fluorouracil versus methotrexate in advanced squamous-cell carcinoma of the head and neck: a Southwest Oncology Group study.

PURPOSE: The Southwest Oncology Group (SWOG) conducted a randomized comparison of cisplatin plus fluorouracil (5-FU) and carboplatin plus 5-FU versus single-agent methotrexate (MTX) in patients with recurrent and metastatic squamous-cell carcinoma (SCC) of the head and neck. The primary objective was to compare separately the response rates of each combination regimen to standard weekly MTX. PATIENTS AND METHODS: Two hundred seventy-seven patients diagnosed with SCC of the head and neck were randomized to one of three treatments: (1) cisplatin 100 mg/m2 intravenously (IV) on day 1 and 5-FU 1,000 mg/m2 per day for a 96-hour continuous infusion repeated every 21 days; (2) carboplatin 300 mg/m2 IV on day 1 and 5-FU 1,000 mg/m2 per day for a 96-hour continuous infusion repeated every 28 days; and (3) MTX 40 mg/m2 IV given weekly. RESULTS: All three treatment regimens were well tolerated. However, both hematologic and nonhematologic toxicities were significantly greater with cisplatin plus 5-FU compared with MTX (P = .001). Toxicity from carboplatin plus 5-FU was intermediate compared with the other regimens. The complete and partial response rates were 32% for cisplatin plus 5-FU, 21% for carboplatin plus 5-FU, and 10% for MTX. The comparison of cisplatin plus 5-FU to MTX was statistically significant (P less than .001), and the comparison of carboplatin plus 5-FU to MTX was of borderline statistical significance (P = .05). Median response durations and median survival times were similar for all three treatment groups. Logistic regression models showed that only treatment assigned was associated significantly with response (P = .001). Cox proportional hazards models indicated that only performance status was associated significantly with survival (P less than .01). CONCLUSIONS: We conclude that combination chemotherapy resulted in improved response rates but was associated with an increased toxicity and no improvement in overall survival. Therefore, new treatments that may alter the course of disease in recurrent head and neck cancer patients still need to be identified.

Effects of a beta-human chorionic gonadotropin subunit immunogen administered in aqueous solution with a novel nonionic block copolymer adjuvant in patients with advanced cancer.

The clinical and immunological effects of a vaccine consisting of CTP37, a synthetic peptide corresponding to the COOH-terminal peptide (CTP) of beta-human chorionic gonadotropin (beta-hCG) conjugated to diphtheria toxoid, combined with CRL 1005, a novel synthetic nonionic block copolymer adjuvant, were examined. Twenty-one patients with metastatic, nontrophoblastic cancers received up to four immunizations by i.m. injection of a fixed dose of CTP37 and escalating doses of CRL 1005. Doses of CRL 1005 adjuvant as high as 75 mg were administered with 1 mg of CTP37 without evidence of significant local or systemic toxicity. Immunizations resulted in the production of IgG antibody to beta-hCG. CRL 1005 doses of 3-25 mg appeared to be optimal for antibody induction. Immunizations also resulted in increases in the cellular response of peripheral blood mononuclear cells (PBMCs) to the unconjugated CTP, hCG, and diphtheria toxoid. Responding PBMCs specifically secreted the TH1-associated cytokines IFN-gamma and interleukin (IL)-2 as well as the TH2-associated IL-5 and IL-10. Increased expression of IFN gamma and IL-5 mRNAs by PBMCs 4 h after immunization was also observed. CRL 1005 administered with CTP37 in aqueous solution is well tolerated. The CTP37-CRL 1005 subunit vaccine has the capacity to stimulate potentially beneficial humoral and cellular immune responses in patients with advanced cancer.

Phase I trial of recombinant interleukin 3 before and after carboplatin/etoposide chemotherapy in patients with solid tumors: a southwest oncology group study.

Recombinant human interleukin 3 (rhIL-3, expressed in Escherichia coli) is a hematopoietic growth factor with protean biological effects on bone marrow in animal models, including enhanced granulocyte and platelet production and the capacity to ameliorate chemotherapy-induced bone marrow toxicity. We, therefore, undertook a Phase I trial in patients with advanced solid tumors and normal bone marrow function. Cohorts of four to six patients each received daily s.c. doses of rhIL-3 (SDZ-ILE-964; Sandoz) at dose levels of 1. 0, 2.5, 5.0, and 10.0 microgram/kg according to the following schedule: cycle 1, rhIL-3 days 1-14; cycle 2, carboplatin (350 mg/m2) on day 1 and etoposide (100 mg/m2) on days 1-3; and cycle 3, carboplatin (350 mg/m2) on day 1, etoposide (100 mg/m2) on days 1-3, and rhIL-3 on days 4-17. Each cycle was a total of 28 days. An analysis of 20 patients entered into all four escalating dose levels revealed that, during cycle 1, absolute neutrophil count (ANC) increased from a median baseline of 6,643/mm3 to a median of 12,692/mm3, and platelets increased from a median baseline of 314,000/mm3 to a median of 465,000/mm3. When cycle 2 was compared with cycle 3, the median ANC nadir increased from 192/mm3 to 988/mm3, and the mean ANC nadir increased from 458/mm3 to 1,297/mm3. Median platelet count nadirs increased from 29,000/mm3 to 84,000/mm3, and the mean nadir platelet counts increased from 72,000/mm3 to 129,000/mm3. Total days on which platelets were <50,000/mm3 was 52 for cycle 2 and 19 for cycle 3. The maximum tolerated dose of rhIL-3 was 5.0 microgram/kg/day; dose-limiting toxicities included fatigue, chills, fever, and headache. These data suggest a clear but variable biological activity observed with IL-3, as measured by the reduction in the depth and duration of thrombocytopenia and/or neutropenia when cycle 2 was compared with cycle 3. rhIL-3 is a promising cytokine that may help to ameliorate the bone marrow toxicity observed with the use of chemotherapeutic agents.

Phenotypic and functional differences between human dendritic cells derived in vitro from hematopoietic progenitors and from monocytes/macrophages.

We compared dendritic cells (DC) derived from CD34+ hematopoietic progenitor cells with tumor necrosis factor alpha and granulocyte-macrophage colony-stimulating factor (GM-CSF) to DC derived from monocytes/macrophages with interleukin-4 (IL-4) and GM-CSF. Monocyte/macrophage-derived DC demonstrated higher levels of CD1a, lower levels of CD14, greater stimulatory activity in mixed lymphocyte reactions, and greater capacity to present soluble protein antigen than CD34+ cell-derived DC. Lymphocytes stimulated with antigen-pulsed, monocyte/macrophage-derived DC produced more IL-10 than those stimulated with antigen-pulsed, CD34+-derived DC. Whereas CD1a+ DC could be derived from CD34+ cells in serum-free- and human-sera-containing cultures, the derivation of CD1a+ DC from monocytes/macrophages required the presence of fetal calf serum. The spectrum of cytokine mRNA expression, the presentation of peptide antigen, and the sensitivity to human immunodeficiency virus-1 infection of CD34(+)- and monocyte/macrophage-derived DC were comparable. Although cells derived by both methods are potent antigen-presenting cells, there are differences between DC derived in vitro from hematopoietic progenitors and from monocytes/macrophages that may influence their in vivo activity.

Modulation of leukemic cell sensitivity to lymphokine-activated killer cytolysis: role of intercellular adhesion molecule-1.

The role of CD11/CD18 leukocyte adhesion molecules and their ligands in mediating non-major histocompatibility complex (MHC) restricted lymphocyte cytotoxicity is controversial. In order to examine the role of target cell intercellular adhesion molecule-1 (ICAM-1; CD54), a ligand of lymphocyte function-associated antigen (LFA-1) (CD11a/CD18), we exposed the human leukemia cell line, HL-60, to a variety of agents implicated in modulating ICAM-1 expression and/or sensitivity to lymphocyte cytolysis. Exposure of HL-60 cells to retinoic acid (RA), interferon (IFN)-alpha, IFN-beta, and IFN-gamma induced protection from lymphokine-activated killer (LAK) cytolysis. Only RA and IFN-gamma induced ICAM-1 expression. Tumor necrosis factor and vitamin D3, which also induced ICAM-1 expression, increased HL-60 sensitivity to LAK lysis. Granulocyte-macrophage colony-stimulating factor also increased sensitivity to LAK lysis; ICAM-1 was not induced. The state of cellular differentiation and expression of class I and II MHC antigens also did not correlate with sensitivity to LAK cytolysis. Exposure of untreated HL-60 cells and HL-60 cells expressing ICAM-1 to monoclonal antibody (mAb) versus ICAM-1 did not modulate LAK sensitivity. Exposure of LAK cells to mAb versus LFA-1 partially inhibited cytolysis; mAb versus CD18 inhibited cytolysis more completely. HL-60 cells were resistant to natural killer lysis; exposure to the various experimental agents did not alter sensitivity. We conclude that leukemic cell sensitivity to LAK cytolysis can be modulated by a variety of agents. Although our results suggest a role for leukocyte CD11/CD18 adhesion molecules in LAK cytolysis, the poor correlation between ICAM-1 expression and sensitivity to LAK lysis suggest that interactions other than LFA-1/ICAM-1 conjugation may be more central to the processes involved.

HIV type 1-reactive chemokine-producing CD8+ and CD4+ cells expanded from infected lymph nodes.

The chemokines RANTES, MIP-1alpha, and MIP-1beta have been identified as HIV-1-suppressive factors produced by CD8+ T cells. We examined the possibility that HIV-1-specific, chemokine-releasing T cells could be expanded from the lymph nodes of patients with advanced infection. Lymphocytes, separated from lymph nodes of patients with peripheral blood CD4 counts less than 500/microl obtained at diagnostic biopsies, were activated with anti-CD3 monoclonal antibody, and cultured in vitro for up to 12 days with IL-2. The phenotype, proliferative response, chemokine production, and anti-HIV-1 activity of the expanded cells was examined. Cells expanded 2.4- to 49-fold from patients with as few as 15 CD4+ cells/microl in their peripheral blood. Expanded cells were a mixture of CD8+CD45RO+ and CD4+CD45RO+ T cells. The CD8+ cells were also CD30+CDw60+CD11b-. When challenged with autologous B cell targets expressing HIV-1 Env protein, unseparated expanded cells, and purified CD8+ and CD4+ T cell subsets, proliferated and secreted MIP-1alpha and RANTES. Expanded cells were negative for HIV-1 by PCR and by culture. Culture supernatants inhibited the replication of HIV-1 in CD4+ cells in vitro. These studies indicate that HIV-1 can stimulate chemokine release by CD8+ and CD4+ cells expanded from infected lymph nodes, even from individuals with advanced infection. The numbers of chemokine-releasing T cells produced in these short-term cultures may be sufficient to be applied therapeutically as an autologous cellular therapy for HIV-1.

Optimum management of nausea and vomiting in cancer chemotherapy.

Nausea and vomiting continue to be critical problems in cancer chemotherapy, although considerable progress has been made toward understanding the neuropharmacological mechanisms of vomiting and how chemotherapeutic agents and antiemetics affect these mechanisms. The principles of behavioural psychology have also been applied in an effort to understand and effectively manage these complications which have potentially serious consequences. For example, there is now some degree of rationality to our use of metoclopramide for cisplatin-induced nausea and vomiting, the use of combination antiemetic regimens, and use of lorazepam for the prevention (albeit unproven) of anticipatory nausea and vomiting. It must be admitted, however, that our approach is for the most part still empirical. Selecting an antiemetic programme is not a simple task. The emetogenic potential of the chemotherapy being used, the presence of coexisting diseases, the potential toxicity of the antiemetic drug and whether antiemetic therapy is to take place in the hospital or in an outpatient setting, the familiarity of the clinician with the various antiemetic therapies, and cost are all factors which need to be considered. Although phenothiazines remain the standard treatment, they are of little value against chemotherapy programmes that produce moderate or severe problems. Newer pharmacological approaches including butyrophenones, cannabinoids, metoclopramide, high-dose corticosteroids, and benzodiazepines have shown increased antiemetic efficacy, as have combinations of these agents which are directed against multiple sites of emetogenic activity. The role of behavioural therapies, which have been shown to be effective particularly in children and in anticipatory nausea and vomiting, needs to be more firmly established. Rather than recommending a given antiemetic programme for any particular chemotherapy, it is preferable to think in terms of initial approaches and how they can be modified. No one antiemetic programme is effective or safe in all situations.

Combined effects of interferon and steroid hormones on 2',5'-oligoadenylate synthetase activity in chronic lymphocytic leukemia cells.

2',5'-oligoadenylate synthetase (OAS) has been implicated in the effects of interferons (INF) and steroid hormones on cell growth and differentiation. We studied the combined effects in vitro of hormones and INF on OAS activity in cells from 10 patients with chronic lymphocytic leukemia. IFN enhanced OAS activity in all cells studied and also induced morphologic transformation. Diethylstilbestrol was also found to induce OAS activity, but not morphologic transformation. Progesterone, tamoxifen and dihydrotestosterone had no effect on enzyme activity nor on morphology. In five samples, all with estrogen receptor activity, DES and INF were synergistic in inducing OAS activity. TAM-INF synergism was observed in one sample. DES and TAM did not, however, significantly enhance IFN-induced morphologic transformations. Hydrocortisone reduced OAS activity, and antagonized INF-induced enzyme activity and morphologic transformations. We conclude that hormones can modulate OAS activity in CLL cells. These findings may be of importance in the design of INF-based therapies of CLL.

Clinical and immunological effects of a synthetic Beta-human chorionic-gonadotropin vaccine.

We treated 23 patients with non-trophoblastic cancers with escalating doses of a synthetic vaccine consisting of the carboxy-terminal peptide of beta human chorionic gonadotropin conjugated to diphtheria toroid (CTP37), a muramyl dipeptide as an adjuvant, and squalene/mannide monooleate as a vehicle. Toxicity consisted of pain and sterile abscess formation at the injection site and of constitutional symptoms. Diphtheria toxoid hypersensitivity developed in one patient. Immunizations elicited anti-beta hCG IgG antibody which persisted for more than 10 months. Disappearance of circulating hCG present pre-immunization and tumor regressions were observed. Active specific immunotherapy with CTP37 vaccine is well-tolerated and has biological activity in patients with cancer.

Antitumor and accessory immune activities of peripheral blood stem cells mobilized with granulocyte-macrophage colony-stimulating factor.

The characteristics of PBSC mobilized with GM-CSF, which has been shown to augment monocyte/macrophage (Mo/Mx) antitumor and accessory activities, were evaluated. Patients with metastatic cancers were treated with GM-CSF at 5 micrograms/kg sc, days 1 to 7; leukaphereses were performed on days 6 and 7. A mean of 3.3 x 10(10) mononuclear cells were collected, 59% of which were lymphoid and 32%, monocytoid. Spontaneous Mo/Mx tumor cell cytotoxicity was not detectable in the leukapheresis product, either before or after cryopreservation; Mo/Mx tumor cell cytotoxicity, however, was inducible in vitro with IFN-gamma. Likewise, spontaneous lymphocyte cytotoxicity was not detectable in the leukapheresis product; lymphokine-activated killer cell activity was inducible in vitro with IL-2. Whereas lymphoproliferative responses to tetanus toxoid of cryopreserved PBSC were less than that of freshly collected PBSC, the capacity of Mo/Mx from cryopreserved PBSC to function as accessory cells in the lymphoproliferative response was maintained. These results indicate that significant numbers of immune cells can be mobilized with GM-CSF alone. Cryopreserved, GM-CSF-mobilized PBSC do not demonstrate spontaneous antitumor cytolytic activity; however, accessory activity is present and antitumor cytolytic activity mediated by both monocytoid and lymphoid cells is inducible.

Human chorionic gonadotropin as a target for cancer vaccines.

Human chorionic gonadotropin (hCG) is expressed by common cancers and may play a role in cell transformation as well as angiogenic, metastatic, and immune escape phenomena that are central to cancer progression. Clinical trials with a vaccine targeting the carboxy-terminal peptide of -hCG have indicated that tolerance to this oncofetal antigen can be broken. Humoral responses that may modulate the biologic activity of tumor-associated hCG as well as cellular responses to hCG have been generated. Studies are in progress to further define the biologic significance of hCG in cancer and to develop a vaccine approach that will best target this expression.

Treatment strategies for AIDS-related malignancies.

We have made progress in the therapy of AIDS-related malignancies, although it is obvious that our treatment strategies, at present, are not--by any measure--satisfactory. Effective treatment should take into account the pathogenesis and etiology of the malignancy; immune and performance status of the patient; the rate of progress of the tumor; the presence or risk of developing life-threatening opportunistic infections; associated hematologic, neurologic, pulmonary, and gastrointestinal abnormalities; the toxicities of treatment; and, most importantly, the patient's desire for treatment. Aggressive supportive measures must be used. With optimal management, it should be increasingly possible to improve the outcome of patients with AIDS-related malignancies.

Radioimmunoguided surgery for colorectal cancer.

This article provides a basic understanding of the RIGS (radioimmunoguided surgery) technique and reviews the evolution of the technology from its inception as an experimental technique in animal models to the current clinical trials in patients. A review of published data from the laboratory and from preclinical and clinical trials is updated by a statement of the current status of RIGS. A look at the future of RIGS as an experimental and clinical tool highlights current areas of investigation based on this technology.

Supportive care of the patient with cancer.

In assessing the needs of the elderly patient with cancer, we need first to determine the extent of cancer, its complications, and the type of comorbid physical and psychologic conditions. The next step is to determine the goals of our care and specifically the extent to which supportive care is needed to deal with problems. For supportive care to be truly effective, the specific underlying condition producing a complaint must be investigated. It is also important not to underestimate the significance of a symptom such as constipation. Furthermore, nutritional support requires as much planning as, for example, the control of pain. Some problems (eg, nausea, vomiting, pain, and constipation) are best managed with preventive measures; others (eg, anemia, granulocytopenia, and coagulopathies) have very specific indications for intervention. Considerable progress has been made toward understanding the mechanisms of clinical problems such as nausea and vomiting, and a more rational approach to supportive therapy is now possible. However, it is usually not possible to recommend any one intervention for a particular problem: no one intervention is uniformly effective or safe. Aggressive supportive care in elderly cancer patients can improve their ability to tolerate anti-cancer therapies and, more importantly, provide palliation of distressing symptoms.