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Biomedical subjects

E M Hersh

Publications and source records attributed to E M Hersh.

At least 19 recordsLinked to original sources
PubMed1992

Long-term engraftment of fresh human myeloma cells in SCID mice.

Using highly purified myeloma cells from patient bone marrow, we established human-murine myeloma chimeras in severe combined immunodeficiency (SCID) mice and documented secretion of monoclonal human immunoglobulins (Hulgs) in the mice for up to 299 days. Monoclonality of circulating Hulgs was found only when highly purified myeloma cells were injected intraperitoneally. In contrast, injection of unfractionated myeloma marrow led to the development of polyclonal Hulgs in the SCID mice. The criteria for myeloma engraftment included prolonged presence of monoclonal Hulgs in the sera of SCID mice and/or detection of human myeloma cells in their tissues by immunohistochemical examination. Ninety-one percent (10/11) of the fresh purified myeloma specimens engrafted in the SCID mice. Fifty-five percent (6/11) of the patient samples resulted in human B-cell grafts, and 45% (5/11) were identifiable as human myeloma chimeras. Pathologic studies showed that most human plasmacytes were located in the peritoneal cavity but metastatic infiltrates were also found in other organs in 69% of the SCID-human myeloma chimeras. This chimeric model should provide a useful tool for characterization of growth modulation and microenvironmental interactions as well as a means of testing new therapeutic approaches to multiple myeloma.

Adult↗
PubMed1992

Antiproliferative and antitumor activity of the 2-cyanoaziridine compound imexon on tumor cell lines and fresh tumor cells in vitro.

BACKGROUND: Imexon, a 2-cyanoaziridine, is therapeutic and reverses lymphadenopathy and splenomegaly in the LP-BM5 murine retrovirus-induced immunodeficiency disease (murine AIDS). It can restore chemotherapy-induced immunosuppression. Imexon reduced the incidence of lymphoma in severe combined immune deficient mice inoculated with human lymphocytes. PURPOSE: To determine its antitumor activity, we screened imexon against fresh human tumor cells and tumor cell lines. To determine the time-concentration relationships of its cytotoxicity, we studied the effects of imexon on macromolecular synthesis and on the cell cycle. METHODS: Imexon was incubated at 1-200 micrograms/mL with various tumor cell lines, mitogen-stimulated peripheral blood lymphocytes, and fresh tumor cells. Cell survival, macromolecular synthesis, and cell cycle progression were studied. RESULTS: The concentration of imexon that caused 50% inhibition of growth was under 10 micrograms/mL for lymphocytes stimulated with mitogens. It was about 3-10 micrograms/mL for B-cell lymphomas and both multi-drug-resistant and -sensitive myeloma cell lines. Imexon inhibited four of seven fresh lymphoma and 11 of 16 fresh myeloma biopsy specimens to less than 40% of the control. A 1-hour exposure of lymphoma cells to 50-100 microgram/mL followed by removal of drug by washing the cells and continuing culture resulted in greater than 95% inhibition during the next 48-72 hours. Imexon selectively inhibited protein synthesis during the first 24-48 hours of exposure of lymphoma and myeloma cells. Cells exposed to inhibitory concentrations of imexon were blocked in cell cycle progression. CONCLUSION: Imexon may be a potentially useful agent in the treatment of malignant disease, particularly lymphoid malignancies, and should be explored further.

Antineoplastic Agents↗
PubMed1992

Expression of type IV collagenase correlates with the invasion of human lymphoblastoid cell lines and pathogenesis in SCID mice.

An in vitro model, called the Membrane Invasion Culture System (MICS), was used to study the invasive potential of an Epstein-Barr virus (EBV) positive lymphoblastoid cell line (LCL), an EBV-negative Burkitt lymphoma (BL) cell line of American origin and an EBV-positive BL of African origin. MICS measured the ability of these cell lines to invade reconstituted basement membrane-coated filters, which correlated with their tumorigenic and metastatic capabilities in a SCID mouse model. Furthermore, the significantly greater invasive behaviour of the EBV-positive LCL was directly correlated with the cells' ability to express and secrete human type IV collagenase (72 kDa), an important metalloproteinase responsible for the degradation of collagen IV in basement membranes. The data suggest that MICS and the SCID mouse are useful tests of tumorigenicity in lymphoid cells, with measurable effects in both systems related to human type IV collagenase activity. Both models allow further exploration of malignant phenotypes associated with EBV transformation of lymphoid tissues.

Animals↗
PubMed1992

Treatment of the murine, retrovirus-induced lymphoproliferative immunodeficiency disease (LP-BM5) in C57BL/10 mice with the immunomodulator Imexon.

Imexon (4-imino-1, 3-diazabicyclo-(3.1.0)-hexan-2-one) a cyanoaziridine compound was studied in the treatment of the murine retrovirus-induced immunodeficiency disease model of AIDS (LP-BM5, MAIDS). Imexon, in dose-dependent fashion, partially prevented the development of hypergammaglobulinemia and splenomegaly, and partially prevented the decline in the phytohemagglutinin-induced proliferative response of spleen lymphocytes when started 1 or 15 days after virus inoculation. There was a statistically significant reduction in these disease-associated manifestations. When animals were treated starting 78 or 92 days after virus inoculation, lymphadenopathy was completely abrogated and survival was significantly prolonged in a dose-responsive manner. Since Imexon and other cyanoaziridine compounds have been safely administered to humans, we suggest that this class of compounds be further investigated in both large animal models of HIV infection and in patients with HIV-induced disease.

Animals↗
PubMed1992

High incidence of coagualopathy in phase II studies of recombinant tumor necrosis factor in advanced pancreatic and gastric cancers.

This multi-center trial was carried out to assess the therapeutic potential of recombinant tumor necrosis factor (rTNF) as the first form of systemic therapy for advanced carcinomas of gastric and pancreatic origin. To be eligible patients were required to have no overt sign of coagulopathy and hepatic function studies with enzymes less than two times beyond the normal range. Twenty nine patients with gastric cancer and 26 with pancreatic cancer were entered from various institutions in the Southwest Oncology Group with 27 and 22, respectively, meeting eligibility criteria. Drug treatment consisted of rTNF (Genentech) given at a dose of 150 micrograms intravenously for five consecutive days every 3 weeks; 50% dose reduction was made for acute intolerance such as hypotension or severe fever and chills. Although eight patients with gastric cancer and five patients with pancreatic cancer received four or more courses of treatment, no objective antitumor responses were recorded. As in other trials common toxicities of rTNF included nausea and vomiting, chills and fever, hypotension, headache, myalgias, fatigue and malaise. However, in this trial, other toxicities became prominent: four episodes of symptomatic disseminated intravascular clotting occurred among patients with pancreatic cancer. Eleven with this disease and five with gastric cancer manifested laboratory findings of abnormal amounts of fibrin split products, and/or hypofibrinogenemia, and/or thrombocytopenia after treatment began. Other laboratory abnormalities that were commonly encountered included hyperglycemia, hypertriglyceridemia, anemia, neutropenia and an elevation in liver enzymes. We conclude that rTNF does not demonstrate antitumor efficacy against adenocarcinomas of the stomach and the pancreas.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Generation and characterization of a human monoclonal antibody that neutralizes diverse HIV-1 isolates in vitro.

OBJECTIVE: The purpose of this study was to develop and characterize human monoclonal antibodies (HuMAb) that neutralize HIV-1. DESIGN: Based upon previous studies involving the generation of HuMAb that neutralize other enveloped viruses, we thought it feasible to generate HuMAb that might neutralize HIV-1. METHODS: A HuMAb was generated by fusing splenic B-cells from an HIV-positive patient with a mouse myeloma cell line. Flow cytometry was used to determine surface reactivity of the HuMAb on HIV-infected and non-infected cells. Radioimmunoprecipitation was employed to elucidate the antigen recognized by the HuMAb. A cell survival assay was used to determine the ability of the HuMAb to neutralize divergent isolates of HIV-1 in the presence or absence of complement. A gp120-CD4 inhibition enzyme-linked immunosorbent assay (ELISA) was developed in order to initiate studies to determine the mechanism of neutralization by the HuMAb. RESULTS: An anti-HIV HuMAb was generated that neutralized two HIV-1 isolates (IIIB and MN) without complement and which neutralized one divergent isolate (RF) and one clinical isolate in the presence of complement. This HuMAb, designated S1-1, was found, by flow cytometric analysis, to react with the surface of HIV-1-infected but not with uninfected cells. Radioimmunoprecipitation analysis demonstrated that S1-1 binds to native HIV gp120, but not dithiothreitol (DTT)-treated gp120. In addition, HuMAb S1-1 did not bind to denatured HIV antigens in Western blot analysis. HuMAb S1-1 effectively inhibited the binding of gp120 to soluble CD4 in ELISA. CONCLUSIONS: These results suggest that the epitope recognized by S1-1 is conformational and conserved among diverse HIV-1 isolates and may represent an uncharacterized HIV neutralizing domain within or close to the CD4 binding domain on gp120. HuMAb S1-1 might have a role to play in vaccine development or passive immunotherapy.

Antibodies, Monoclonal↗
PubMed1992

A Southwest Oncology Group Phase I study of the sequential combination of recombinant interferon-gamma and recombinant interleukin-2 in patients with cancer.

Thirty-seven patients with advanced malignancies were treated sequentially with recombinant interferon-gamma (rIFN-gamma) and recombinant interleukin-2 (rIL-2) in an outpatient dose escalation clinical trial. rIFN-gamma (0.1 or 0.25 mg/m2/day) was administered by intramuscular injection, days 1-7 and rIL-2 (12, 18, or 24 x 10(6) IU/m2/day) was administered by a 15-min intravenous bolus, days 8-12. Common toxicities encountered included fever, chills, fatigue, neutropenia, and elevations of SGOT, bilirubin, or creatinine. Hypotension and cardiac and pulmonary toxicities were rare. With repeated cycles of therapy, nausea/vomiting and diarrhea associated with the administration of rIL-2 were seen in greater frequency. There were no treatment-related deaths, and no patient required intensive care unit admission for toxicity management. A complete response was observed in one of 11 patients with renal cancer and a partial response was observed in one of seven patients with malignant melanoma. Due to problems with drug supply, further dose escalation could not be continued, and maximum tolerated doses (MTD) were not determined by strict criteria. However, the combination of rIFN-gamma, 0.25 mg/m2/day, and rIL-2, 24 x 10(6) IU/m2/day, appeared to be beyond the MTD, as three of six patients at this dose level could not complete one cycle of therapy due to toxicity. It is unlikely that higher doses of either agent would be tolerated, and for further study using this schedule, we recommend the doses: rIFN-gamma, 0.1 mg/m2/day, and rIL-2, 24 x 10(6) IU/m2/day.

Adult↗
PubMed1992

Phase I study of low-dose cyclophosphamide and recombinant interleukin-2 for the treatment of advanced cancer.

We conducted a phase I study of low-dose cyclophosphamide and recombinant interleukin-2 (rIL-2) in 66 patients with advanced cancer resistant to standard therapy. All patients were evaluable for toxicity and 46 patients were evaluable for antitumor response. Patients evaluable for antitumor response included 23 with malignant melanoma, 10 with renal cell carcinoma, 4 with colon cancer, and 9 with various other solid tumors. All patients received i.v. cyclophosphamide (350 mg/m2) on day 1 followed by rIL-2 via 15 min i.v. infusion on days 4-8 and 11-15. The doses of rIL-2 ranged from 6.0 to 36.0 x 10(6) IU/m2. Each treatment cycle consisted of 21 days and a total of 113 cycles was administered. The number of treatment cycles administered per patient ranged from 1 to 8. The dose-limiting toxicities associated with rIL-2 included altered mental status, arthralgias, diarrhea, fatigue, fever, hypotension, nausea/vomiting, and peripheral edema. Twelve patients (18%) were removed from the study secondary to toxicity. Among the evaluable patients, 2 (4%) (malignant melanoma, renal cell carcinoma) developed a partial remission, 13 (29%) maintained stable disease, and 31 (67%) developed progressive disease. We conclude that the combination of low-dose cyclophosphamide and rIL-2 is tolerable in most patients but our data do not suggest an improved response rate for the combination vs. rIL-2 alone.

Adolescent↗
PubMed1992

Interferon-gamma induced by administration of recombinant interleukin-2 to patients with cancer: kinetics, dose dependence, and correlation with physiological and therapeutic response.

The administration of recombinant interleukin-2 as an i.v. bolus at dose levels of from 1 to 30 MIU/m2 to patients with cancer induces easily measurable serum interferon-gamma levels of 1 to 500 U/ml. After a lag of 1 h, interferon-gamma rises to a maximum at 4 h and then slowly decreases. The peak values are poorly correlated with the dose of interleukin-2, and thus must be also be dependent on other factors. Successive administration of interleukin-2 typically increases the peak level of interferon-gamma fourfold, but does not diminish the lag period. Peak levels of interferon-gamma are also increased by concurrent administration of interferon-beta with interleukin-2. Continuous i.v. infusion of 1.5 to 20 MIU/m2 of interleukin-2/day results in interferon-gamma levels of 1 to 7 U/ml. Hypotension, which is characteristically associated with interleukin-2 administration, is correlated with interferon-gamma levels in only some patients. There was no apparent correlation between tumor regression and serum interferon-gamma levels.

Blood Pressure↗
PubMed1992

A phase I trial of fluorouracil, leucovorin, and recombinant interferon alpha-2b in patients with advanced malignancy.

We conducted a phase I trial of fluorouracil (5-FU), leucovorin, (LCV), and recombinant interferon-alpha-2b (rIFN-alpha-2b). The doses of each of the three agents were escalated sequentially. 5-FU and LCV were administered by IV bolus, weekly for 6 weeks and rIFN-alpha-2b was administered by subcutaneous injection, three times weekly for 6 weeks. Twenty-nine patients with advanced cancer (75% colon or pancreatic cancer) were treated. Partial remissions were observed in three patients (10%) with previously untreated colon cancer, colon cancer refractory to 5-FU plus LCV and previously untreated pancreatic cancer, respectively. An additional three patients with pancreatic, prostate, and rectal cancer had a 50% reduction in tumor markers but no change in objective tumor measurements. The toxicity of this regimen was tolerable. The most common toxicities were diarrhea, fatigue, flu-like symptoms, nausea/vomiting, and mucositis. However, no fatal or life-threatening toxicities were observed. We conclude that the combination of 5-FU, LCV, and rIFN-alpha-2b can be safely administered and recommend further evaluation of this regimen in patients with tumors of gastrointestinal origin using doses of 5-FU 600 mg/m2, LCV 500 mg/m2, and rIFN-alpha-2b 10 x 10(6) U.

Adult↗
PubMed1992

Growth and dissemination of human malignant melanoma cells in mice with severe combined immune deficiency.

BACKGROUND: The severe combined immune deficiency (SCID) mouse is lacking mature B and T lymphocytes and may be permissive for human tumor growth and metastasis. EXPERIMENTAL DESIGN: SCID mice received human melanoma cells of diverse origins including: 2 established cell lines, 4 early passage cell lines, and fresh or cryopreserved cells obtained directly from 9 patient biopsies. They were introduced into SCID mice via intraperitoneal, subcutaneous and intravenous injections. RESULTS: Tumor growth occurred with each of the 15 melanoma specimens for a take rate of 100% considering cell source. In addition, 60% of the 102 total mice injected displayed tumor growth in at least one site. The most consistent tumor growth (77%) occurred after intraperitoneal injection. Tumors developed in 41 and 48% of mice injected subcutaneously and intravenously, respectively. The mice developed both local tumor growth with palpable tumor nodules at injection sites and hematogenous and/or lymphatic dissemination to multiple sites in the abdominal and thoracic cavities. The number of metastases per animal averaged 16.3 and the number per organ ranged from 1 to 38. Melanotic and amelanotic tumor nodules obtained from a single patient retained their original characteristics with regard to melanin production after passage in the SCID mouse. The appearance of the human melanoma cells in SCID mouse tissues ranged from implants on the organ capsule to frank parenchymal organ involvement and vascular invasion. Some small foci of tumor were only detected using immunohistochemistry with monoclonal antibodies against the S-100 and HMB-45 to melanoma-related antigens. CONCLUSIONS: We conclude that the SCID mouse consistently supports growth, invasion, and metastatic spread of human melanoma cells, including specimens obtained from fresh patient biopsies. The SCID mouse will serve as a relevant in vivo model for studying the biology of human malignant melanoma and screening new therapeutic agents.

Animals↗
PubMed1991

In vitro efficacy of anti-HIV immunotoxins targeted by various antibodies to the envelope protein.

Six different anti-HIV envelope antibodies and one irrelevant control antibody were coupled to ricin A chain and tested for their efficacy in inhibiting HIV tissue culture infections. The anti-HIV antibodies consisted of five monoclonals, three of murine and two of human origin, and one polyclonal preparation prepared by affinity purifying pooled serum antibodies from HIV-infected humans on rgp160. The binding specificity of the antibodies was defined by ELISA by using recombinant envelope proteins and synthetic peptides, and by flow cytometry on HIV-infected cells. The in vitro efficacy of the antibodies was tested by the abilities of the immunotoxins to inhibit protein synthesis in persistently infected cell lines and by their abilities to inhibit HIV production during both acute and persistent infection as measured with an HIV-specific focal immunoassay. The immunotoxins were tested against a panel of distinctly different HIV isolates. The results indicate the following: 1) A mAb to the immunodominant neutralizing loop was highly effective against homologous strains of HIV, but had no activity against heterologous HIV. 2) The efficacy of anti-gp41 mAb varied depending upon the epitope recognized and possibly the affinity of binding to gp41. 3) The polyclonal human anti-gp160 antibodies produced the immunotoxin with the broadest specificity for different HIV strains and the greatest specific activity. This is related to the polyclonal nature of the preparation rather than an increase in relative avidity of the antibody. 4) Activity of an immunotoxin is not a direct function of the binding of the antibody to the surface of infected cells. 5) The ability of an immunotoxin to halt the spread of infection through a tissue culture cell population is dependent upon the ability of the antibody to neutralize the virus as well as the activity of the toxin. Our data suggest that efficacious immunotoxins for the treatment of AIDS may be made with polyclonal anti-envelope antibodies derived from the serum of patients who have been infected with HIV or with appropriately chosen anti-gp41 antibodies.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Ditiocarb sodium (diethyldithiocarbamate) therapy in patients with symptomatic HIV infection and AIDS. A randomized, double-blind, placebo-controlled, multicenter study.

We randomized 389 symptomatic patients with human immunodeficiency virus (HIV) infection to ditiocarb sodium (400 mg/m2 orally for 24 weeks) or a placebo. Patients were well balanced according to Centers for Disease Control (CDC) group, CD4+ cell number, and duration of disease prior to entry. Ten new acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections occurred in the treated patients and 21 in the controls. Reduction of new opportunistic infections in the ditiocarb group was significant in all patients (relative risk [RR], 0.44) and in patients with AIDS (CDC groups IV-C1 and IV-D) (RR, 0.12). The size of the effect of ditiocarb was maintained when data were reanalyzed after exclusion of a patient who progressed to Pneumocystis carinii pneumonia who was not strictly CDC-defined (RR, 0.46), or when considering as new opportunistic infections three events, which were clinically active at entry, but for which the definitive diagnosis was made during study (RR, 0.49). The administration of ditiocarb did not induce any major adverse clinical or biological reactions. We conclude that, in this study, ditiocarb was safe and reduced the incidence of opportunistic infections in patients with symptomatic HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Homotypic antibody responses to fresh clinical isolates of human immunodeficiency virus.

Human immunodeficiency virus type 1 (HIV-1) exhibits extensive genomic and antigenic diversity, which is thought to contribute to the failure of the host's immune response to control infection and prevent clinical progression. Part of this failure may be due to utilization by the virus of antigenic variation as a means to escape protective immune responses. Antibody-escape variants of HIV-1 were studied here using fresh clinical isolates and autologous plasmas. HIV-1 was isolated from the plasma of seven people who were all seropositive for at least 2 years, and symptomatic sometime during that period. Isolated viruses were confirmed as HIV-1 by the presence of reverse transcriptase activity in infected culture supernatants, and by positive immunofluorescence using human monoclonal antibody to HIV-1 core protein. Plasma from these people were positive by Western immunoblot (DuPont) for most major HIV-1 (strain IIIB) antigens. These plasmas neutralized three laboratory strains of HIV-1 (i.e., IIIB, RF, and MN) but did not neutralize the homotypic strain in five cases, and had greatly reduced neutralizing titers against the homotypic strain in two cases. Homotypic neutralizing antibodies were absent in autologous plasma obtained 3 months later. When antibody titers were measured by fixed-cell indirect immunofluorescence assays (IFAs), high titers of IgG (1:6400 to 1:25,600) were detected against HIV-1 IIIB, while low titers of only 1:20 to 1:160 were detected against homotypic viral antigens at the time of virus isolation, and remained low 12 and 16 weeks later. No class IgA, IgD, IgE, or IgM antibodies to homotypic viral antigens, as possible IgG-blocking antibodies, were detected by fixed-cell IFAs. Cross-reactions with heterologous donor's plasmas were observed in some cases, and in these cases the cross-reactions were unidirectional. Live-cell IFAs detected IgG in patient's plasma to HIV-1 IIIB-infected cells but not to cells infected with homotypic isolates. These results suggest that it is common for neutralization-resistant HIV-1 variants to appear during the course of infection, and that all or most antigens of these variants are capable of escaping antibody recognition.

AIDS-Related Complex↗
PubMed1991

Effective therapy of the LP-BM5 murine retrovirus-induced lymphoproliferative immunodeficiency disease with diethyldithiocarbamate.

The effects of therapy with the immunomodulator diethyldithiocarbamate (DTC) on the manifestation and natural history of LP-BM5 murine retrovirus infection in adult C57 Black 6 mice was investigated. DTC itself, had limited effects on the spleen weight, serum IgM, or mitogen responses of the non-virus-infected control mice when evaluated over a 9-week period. The virus inoculum administered was such that there was approximately a twofold increase in serum IgM and a halving of phytohemagglutinin (PHA) and lipopolysaccharide (LPS) responses in about two weeks and death of all animals by about 26 weeks postinfection. Doses of DTC of 20 and 200 mg/kg weekly or 5 days per week (intraperitoneally) in mice with LP-BM5 infection did not alter the manifestations or course of the disease. Doses of 400 or 600 mg/kg given 5 days per week, starting either 2 weeks before or the day of virus inoculation significantly reduced hypergammaglobulinemia, spleen weight, lymphadenopathy, and also prolonged survival. A dose of 400 mg/kg started 2 weeks after virus inoculation resulted in partial prevention of hypergammaglobulinemia, splenomegaly, and lymphadenopathy as well as 100% survival compared with 12.5% in non-drug-treated controls at 23 weeks after virus inoculation. The 9 surviving animals in the treated group were then allocated to continue treatment or stop treatment. In the animals without further treatment, lymphadenopathy and mortality occurred starting within 6 weeks after cessation of therapy while the animals with continued treatment remained in good condition for 40 weeks. There was only a very limited and transient effect of DTC therapy on the decline of the proliferative responses to phytohemagglutinin or lipopolysaccharide in any of the treated groups in the above described experiments.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1990

Antibodies to the primary immunodominant domain of human immunodeficiency virus type 1 (HIV-1) glycoprotein gp41 enhance HIV-1 infection in vitro.

Previous experiments had shown that two human monoclonal antibodies (huMAbs) directed against human immunodeficiency virus type 1 (HIV-1) enhanced HIV-1 infection in vitro (Robinson et al., Proc. Natl. Acad. Sci. USA, 87:3185-3189, 1990). This complement-mediated, antibody-dependent enhancement (C'-ADE) of HIV-1 infection caused 12-fold increases in reverse transcriptase released from MT-2 cells. In the study reported here, it was demonstrated that both of these huMAbs, 86 and V10-9, bound to an immunodominant peptide in gp41 (amino acids 586 to 620). This peptide blocked C'-ADE of HIV-1 infection in vitro regardless of whether huMAb 86 or human polyclonal anti-HIV was used as the source of anti-HIV antibody. Blockade of enhanced infections was characterized by decreases in antigen synthesis, cytopathic effect, and reverse transcriptase release. The ability of the huMAbs to enhance infection was determined to be dependent upon specific peptide reactivity and not dependent upon immunoglobulin subclass, complement fixation, or gross antigen reactivity. Since the peptide to which enhancing antibodies bind is immunodominant and does not bind neutralizing antibodies, it may be worthwhile to investigate deletion of this 35-amino-acid peptide from candidate anti-HIV vaccines.

Amino Acid Sequence↗
PubMed1979

Postoperative adjuvant chemotherapy with fluorouracil, doxorubicin, cyclophosphamide, and BCG vaccine. A follow-up report.

Two hundred twenty-two patients with stage II or III breast cancer following regional therapy were treated with a combination of fluorouracil, doxorubicin hydrochloride (Adrimycin), cyclophosphamide, and BCG vaccine. At 54 months of study (median follow-up, 30 months), the estimated proportions remaining disease-free two and three years after surgery were 83%and 78%, respectively, in the chemotherapy group and 64% and 55%, respectively, in 151 historical control patients. Estimated two- and three-year survival rates were 93% and 89%, respectively, in the chemotherapy group and 84% and 58%, respectively, in the control patients. Congestive heart failure has developed in three patients, possibly related to the use of doxorubicin. Adjuvant chemotherapy with these drugs was effective in prolonging the disease-free interval and survival of patients irrespective of menopausal status, degree of nodal involvement, or stage of the disease.

Antineoplastic Agents↗