Targeting hypoxia in the treatment of small cell lung cancer.

Small cell lung cancer (SCLC) is an extremely aggressive disease for which minimal therapeutic improvements have been made over the last few decades. Patients still rely on non-targeted, chemotherapeutic drugs complemented by irradiation. Although initial response is very good, the majority of SCLC patients invariably relapse with therapy-resistant tumours. Despite the link between pathologically low oxygen levels and therapy resistant tumours, hypoxia has gained little attention in the development of novel therapies for SCLC. In contrast, the advantages of targeting hypoxic cells in many other cancer types have been studied extensively. This review describes the reasons for targeting hypoxia in SCLC and outlines strategies undertaken to enhance hypoxic tumour cell death, including the use of bioreductive prodrugs, the targeting of HIF-1α and the induction of cell death through acidosis. Therapy directed towards hypoxic tumour regions has the potential to greatly enhance the response of SCLC tumours to current treatment regimens and represents an area of research in need of greater attention. Such research could lead to the much sought after development of targeted drugs against SCLC tumours.

Neuroendocrine and epithelial phenotypes in small-cell lung cancer: implications for metastasis and survival in patients.

BACKGROUND: Small-cell lung cancer (SCLC) has a very aggressive clinical course with early metastasis. This study investigated how the distinctive neuroendocrine characteristics contribute to disease progression and invasion in human SCLC. METHODS: The neuroendocrine phenotype (pro-opiomelanocortin (POMC)) was quantified by ELISA in blood samples from 43 SCLC patients. The neuroendocrine (POMC, chromogranin A, neuron-specific enolase, NCAM) and epithelial (cytokeratin and E-cadherin) phenotypes were investigated, using ELISA and immunocytochemistry/immunohistochemistry. RESULTS: In SCLC patients, 16% had elevated circulating POMC, which was associated with significantly worse survival (P=0.02) and liver metastases (P=0.004). In addition, POMC correlated with epithelial-positive circulating tumour cells (P=0.0002). In a panel of SCLC cell lines, all POMC-secreting cell lines expressed cytokeratin (40% of total). Even after cloning, DMS 79 cells expressed both neuroendocrine and epithelial markers. DMS 79 xenografts secreted POMC into the blood, which mirrored the tumour volume. These xenografts expressed both neuroendocrine and epithelial phenotypes in all tumours, with both phenotypes prevalent in cells invading the surrounding tissue. CONCLUSION: Both neuroendocrine and epithelial phenotypes coexist in human SCLC tumours in vitro and in vivo and this persists in invading tumour cells. In patients, POMC secretion predicts poor survival and liver metastases, suggesting a crucial role of the neuroendocrine phenotype.

A microRNA gene expression signature predicts response to erlotinib in epithelial cancer cell lines and targets EMT.

BACKGROUND: Treatment with epidermal growth factor receptor (EGFR) inhibitors can result in clinical response in non-small-cell lung cancer (NSCLC) and pancreatic ductal adenocarcinoma (PDAC) for some unselected patients. EGFR and KRAS mutation status, amplification of EGFR, or gene expression predictors of response can forecast sensitivity to EGFR inhibition. METHODS: Using an NSCLC cell line model system, we identified and characterised microRNA (miRNA) gene expression that predicts response to EGFR inhibition. RESULTS: Expression of 13 miRNA genes predicts response to EGFR inhibition in cancer cell lines and tumours, and discriminates primary from metastatic tumours. Signature genes target proteins that are enriched for epithelial-to-mesenchymal transition (EMT) genes. Epithelial-to-mesenchymal transition predicts EGFR inhibitor resistance and metastatic behaviour. The EMT transcription factor, ZEB1, shows altered expression in erlotinib-sensitive NSCLC and PDAC, where many signature miRNA genes are upregulated. Ectopic expression of mir-200c alters expression of EMT proteins, sensitivity to erlotinib, and migration in lung cells. Treatment with TGFß1 changes expression of signature miRNA and EMT proteins and modulates migration in lung cells. CONCLUSION: From these data, we hypothesise that the tumour microenvironment elicits TGFß1 and stimulates a miRNA gene expression program that induces resistance to anti-EGFR therapy and drives lung tumour cells to EMT, invasion, and metastasis.

Effect of Cnidoscolus aconitifolius leaf extract on the blood glucose and insulin levels of inbred type 2 diabetic mice.

The effects of Cnidoscolus aconitifolius (CA) leaf extract and chlorpropamide on blood glucose and insulin levels in the inbred type 2 diabetic mice are reported. After treatment with CA, the glucose levels were measured at 0 and 2-hour intervals in experimental groups and controls. Group I received no treatment and served as control; Group II was the reference and it received chlorpropamide; Groups I-III were moderately diabetic, 100-300 mg/dL blood glucose levels while Group IV were severely diabetic (> 300 mg/dL). Groups III and IV received CA and served as test groups. There was no significant difference between the blood glucose levels at 0 and 2 hours for the control group, (P>0.23) but there were statistically significant differences for Group II (P<0.0002); Group III (P<0.002) and Group IV (P<0.0001). For moderately diabetic mice, CA and chlorpropamide decreased the glucose levels by 25.6% and 16.3% respectively while for the severely diabetic mice CA decreased the blood glucose by 43.7%. It is proposed that CA has an insulinogenic property that possibly stimulated dormant beta-cells to secrete insulin. The histopathology of several organs in the treated animals was found to differ from the expected. The islets of Langerhans for example were found to be preserved in the time frame examined. Also the liver and kidney were found to display milder pathology in the treated groups.

Comparison of the amniotic fluid index with gray-scale and color Doppler ultrasound.

OBJECTIVES: This study was undertaken to compare the amniotic fluid index (AFI) obtained with gray-scale ultrasound and color Doppler. STUDY DESIGN: We examined 77 patients ranging from 22 to 41 weeks' gestation with two of five sonographers obtaining two measures of the AFI utilizing gray-scale and color Doppler. RESULTS: Of the measurements of AFI, 96% showed the gray scale measurement to be greater than the color measurement (p < 0.0001; mean 9.3 +/- 3.3 cm vs. 8.5 +/- 3.0 cm). At gray-scale AFI < 5 cm, color AFI was essentially the same, but at gray-scale AFI 5-10 cm, color AFI was < 5 cm, 15.2% and 7.8% of the time. At gray-scale AFI > 10 cm, no color AFI was < 5 cm. Individual (n = 5) interobserver reliability was r = 0.79 (p < 0.0001) and intraobserver reliability was r = 0.94 (p < 0.0001). CONCLUSIONS: AFI by color Doppler was always less than with gray scale. At an AFI of 5-10 cm, color demonstrated an AFI of < 5 cm in up to 16% of patients, and increased the diagnosis of oligohydramnios.

Congenital nuclear cataracts and uveitis in HIV-transgenic mice.

PURPOSE: Patients infected with HIV-1 develop ocular manifestations, some due to opportunistic infections and others attributed to the virus itself. Among the latter are retinal microvasculopathy and uveitis. We have analysed the ocular phenotype in HIV-transgenic mice. METHODS: We have studied T26 transgenic mice which bear a gag-pol deleted HIV-1 genome. Transgene RNA was detected by Northern analysis. Ocular pathology was assessed by conventional histology, immunostaining for gp120 envelope protein, and in situ apoptosis detection with end-labelling. RESULTS: Abnormalities of lens epithelial cell development were detected as early as embryonic day 14.5. Histological changes included the malformation of an embryonal lens nucleus and poor closure of the lens suture lines. This resulted in congenital nuclear cataracts, as occur in congenital viral infections in human patients. In the adult animals, lenses were notable for extensive vacuolation, liquefaction, and degeneration of the cortex. Mild iridocyclitis and vitritis were also noted in adult transgenic mice. Immunostaining demonstrated the expression of gp 120 envelope protein within the lens epithelial and fibre cells. End-labelling with terminal deoxyribonucleotidyl transferase showed increased numbers of apoptotic cells in the adult lens. CONCLUSIONS: These findings suggest that one or more HIV-1 proteins are associated with congenital nuclear cataract formation and uveitis in HIV-transgenic mice.

Volumetric umbilical artery blood flow: comparison of the normal versus the single umbilical artery cord.

OBJECTIVE: This was a study of the volumetric blood flow in single umbilical artery (SUA) cords as compared to three-vessel cords. HYPOTHESIS: SUA flow will be twice that of an artery in a normal cord. METHODS: We studied 276 patients (24 SUA, 252 normal cord) at 18-40 weeks' gestation utilizing gray-scale and color Doppler. Flow, flow/kg, velocity, artery diameter, Doppler velocimetry indices, estimated fetal weight (EFW) and amniotic fluid index (AFI) were compared. All fetuses were anatomically and cytogenetically normal. RESULTS: Blood flow increased with advancing gestation and the SUA volume was twice that in the normal cord artery. Flow/kg decreased for both cords, with the SUA values twice those of normal cords. Arterial diameter and velocity increased, but to a greater degree in SUA. Velocimetry, although in the normal range, decreased progressively with the resistance indices always lower in the SUA cord. EFW and AFI were the same for both groups. CONCLUSION: Volumetric blood and its components were measured indirectly with ultrasound. The SUA cord artery carried twice the blood volume of an artery in a three-vessel cord. Other flow parameters changed appropriately to explain the increased flow. For the anatomically normal fetus with SUA there was no increase in intrauterine growth restriction.

Reliability of wound measuring techniques in an outpatient wound center.

Wound measurements determine whether treatment(s) should be continued or changed. A busy wound clinic must rely on many different personnel for wound measurements. The realization that using a variety of measurement techniques could effect medical treatment choices raised concerns. To determine the inter-rater reliability of wound measuring techniques used by clinical staff in an outpatient wound center, three approaches to wound measurement were studied with the intent to standardize clinic procedures in the authors' facilities and to use the method with greatest inter-rater reliability. An exploratory descriptive study was initiated in a busy multidisciplinary wound-healing clinic in a northeastern Ohio 500-bed teaching and community hospital. Participants included 16 wound care professionals who staff an outpatient wound center. Inter-rater reliability measures were compared to three measurement techniques. The intraclass correlation coefficient was used as the statistical measure of inter-observer agreement. After comparing measurements made by the usual method used by an individual, the clockwise method, and the perpendicular method, the perpendicular method showed clear superiority in agreement among clinicians (ICC .962; df = 11,143; P = < 0.001) as compared to the clock-wise method (ICC .682; df = 11,154; P = < 0.05). This study provided a basis for standardizing the approach to wound measurement among physicians and nursing personnel and has important implications for effective medical care, research, and healthcare cost savings.

Volumetric flow in the umbilical artery: normative data.

OBJECTIVE: Provide normative data for the volumetric blood flow (cc/min and cc/min/kg) in the umbilical artery. METHODS: Flow was determined from an umbilical artery in 252 normal obstetrical patients from 18-40 weeks' gestation utilizing pulsed Doppler and color flow Doppler with an angle of insonation of 30-60 degrees. Simultaneous velocimetry studies (S/D ratio, resistance and pulsatility indices), fetal biometry, and an anatomic survey were obtained to further define the normal population. RESULTS: There was a steady increase in the flow (cc/min) in the umbilical artery as pregnancy progressed. Flow/kg showed a steady decline as fetal weight increased. Umbilical artery diameter increased until reaching a plateau at 32-34 weeks. Velocimetric results were consistent with known data. CONCLUSIONS: Volumetric blood flow in the umbilical artery can be determined with relative ease and normative data from 18-40 weeks is presented for the first time.

Role of T lymphocytes in renal disease in HIV-transgenic mice.

The pathogenesis of human immunodeficiency virus (HIV)-associated focal segmental glomerulosclerosis (FSGS) has remained obscure. It has been proposed that renal parenchymal cells may be infected with HIV-1. If such infection occurs, the target cells would be expected to express viral proteins and thus could be targets for cytotoxic T lymphocytes. We previously described mice transgenic for a gag-pol-deleted HIV-1 genome that developed FSGS. In the present study, we tested the requirement for functional T cells in the evolution of renal disease in this model. We bred the HIV-transgenic mice (T26) with athymic nude mice to produce athymic T26 mice. We confirmed by flow cytometry of peripheral blood, thymus, lymph node, and spleen that the athymic T26 mice lacked mature T cells. The athymic T26 mice developed renal disease characterized by FSGS, tubular atrophy and dilatation, and interstitial infiltrate that was qualitatively identical to that seen in the parental T26 mice. Quantitative assessment of the athymic T26 mouse kidneys showed that glomerulosclerosis, tubular injury, and interstitial infiltrate were less severe compared with the parental T26 mouse kidneys. Although T26 mouse kidneys had a mixed cellular infiltrate composed of CD4 cells, CD8 cells, and macrophages, interstitial infiltrates within the athymic T26 mouse kidneys included macrophages but lacked both CD4 and CD8 cells. The renal expression of the HIV transgene was 1. 7-fold greater in T26 mice compared with athymic T26 mice. We conclude that mature T cells are not absolutely required for the development of HIV-associated nephropathy in transgenic mice but that, in their absence, renal disease is significantly milder. These data suggest that T-cell-mediated cytotoxicity directed against renal cells expressing virally encoded proteins is not an essential feature of renal pathogenesis in this model.

Drug abuse treatment outcome study of adolescents: a comparison of client characteristics and pretreatment behaviors in three treatment modalities.

OBJECTIVES: The present study presents background and pretreatment characteristics of adolescent substance abuse treatment clients, and it provides a mechanism for describing perhaps the largest research sample of adolescents who were in drug treatment in this decade. METHODS: The sample was 3382 subjects who presented for treatment from 1993 to 1995 in 37 programs in Pittsburgh. Pennsylvania: Miami, Florida; Minneapolis, Minnesota; Chicago, Illinois; Portland, Maine; and New York City, New York. Informed permission for the youth to participate was obtained from the subject's custodial parent/guardian, and both the youth and the youth's parents or guardians provided informed assent if they agreed to participate as subjects. Adolescents then were interviewed privately and confidentially by a trained professional interviewer who was independent of the treatment programs. The interviews queried subjects about their background, including education and employment; physical and mental health; use of tobacco, alcohol, and other drugs; sexual experiences; legal problems: religious beliefs; and treatment experience. RESULTS: The long-term residential treatment modality was the least gender balanced of the modalities and had the most African-American and Hispanic clients. This modality was distinguished by the proportion of clients who were referred to treatment by the juvenile or criminal justice system. Compared with other clients in other modalities, short-term inpatient clients were more likely to be female and white. Inpatient clients also reported more indicators of psychiatric impairment. Outpatient clients were slightly younger than clients in the other modalities, and more of them were attending school at the time of admission to treatment. Outpatient clients had the least criminally involved lifestyles, their rates of (regular daily or weekly) drug use were also the lowest of the three modalities for all drugs assessed, and they had the least drug treatment experience. CONCLUSIONS: These results merit several recommendations. One is the need for more community-based adolescent substance abuse treatment programs. An additional recommendation is for more substance abuse treatment programs in facilities that serve incarcerated youth. Finally, and perhaps most critically, it is recommended that programs be designed to address such specialized issues as comorbid substance abuse and psychiatric problems, family dysfunction, physical and sexual abuse, gender and ethnic differences, and academic performance.

Neoplastic AIDS-associated Kaposi's sarcoma cell line KSY-1 cannot transdifferentiate into capillaries.

OBJECTIVE: Kaposi's sarcoma (KS) is an acquired immunodeficiency syndrome (AIDS)-defining neoplasm histologically characterized by proliferation of spindle cells, inflammatory cells, and abundant neovascularization. When the malignant cell line KSY-1 derived from an AIDS-KS tumor is transplanted subcutaneously into nude mice, prominent neovascular features develop. Using this mouse model of neoplastic KS, we set out to determine, using c-ets 1 markers specific for mouse or human tissues, whether vascular growth and inflammatory infiltrate induced by the transplanted KSY-1 cells is of host cell or transplant origin. STUDY DESIGN/METHODS: KS tumors were induced by subcutaneous inoculation of 5 x 10(6) KSY-1 cells/200 microL in immunodeficient mice, and species-specific mouse and human riboprobes of the c-ets 1 protooncogene were used for in situ hybridization to define cell of origin. RESULTS: Five different tumors were examined. Tissue sections from all cases were hybridized with radiolabeled riboprobes for the presence of both mouse and human c-ets 1 mRNA. Tumor cells were labeled with the human c-ets 1 probe, whereas neovascular and inflammatory tissues were of mouse origin. CONCLUSIONS: The finding that vascular but not tumor cells are of host origin supports the model of tumor-induced vascularization via a mechanism of tumor cell-derived cytokine-medicated pathogenesis.

HIV-1 protease inhibitor ritonavir modulates susceptibility to apoptosis of uninfected T cells.

OBJECTIVE: Clinical experience with HIV-1 protease inhibitors (PIs) in the treatment of AIDS frequently has shown that increases in CD4+ T-cell counts can be independent of HIV-1 inhibition by these drugs. This disconnection between viral load and CD4 counts led us to investigate how the PI ritonavir directly affects leukocyte activation in vitro, using peripheral blood mononuclear cell (PBMC) fractions derived from normal donors. METHODS AND RESULTS: When uninfected PBMC cultures were treated for 72 hours with ritonavir at concentrations similar to or lower than that shown to be effective in vivo, an increase in cell viability was observed. The susceptibility of PBMCs to apoptosis was markedly decreased after ritonavir treatment and correlated with lower levels of caspase-1 expression, decreases in annexin V staining, and reduced caspase-3 activity. Induction in vitro of tumor necrosis factor (TNF) production by PBMCs and monocytes was inhibited by ritonavir in a time- and dose-dependent manner at nontoxic concentrations. CONCLUSION: Based on our data, we conclude that the HIV-1 PI ritonavir is an immune modulator that may affect leukocyte activation and apoptosis as an important part of its therapeutic benefit.

Induction of programmed cell death in Kaposi's sarcoma cells by preparations of human chorionic gonadotropin.

BACKGROUND: Isolation of the first neoplastic acquired immunodeficiency syndrome-related Kaposi's sarcoma (KS) cell line (KS Y-1) has furthered understanding of the pathogenesis of KS. Studies with KS Y-1 cells have indicated that inhibition of KS cell proliferation occurs in early pregnancy in mice and after treatment with certain commercial preparations of human chorionic gonadotropin (hCG, a pregnancy hormone purified from urine). The activity of the commercial preparations has been attributed to an hCG-associated factor(s) (HAF). While several clinical benefits of HAF are clearly evident, the basis for its anti-KS properties remains unknown. We investigated the apoptosis-inducing effects of HAF and the expression of apoptosis-related proteins in KS cells. METHODS: KS Y-1 and KS SLK cells were treated with clinical-grade crude preparations of hCG, recombinant hCG, or urine fractions exhibiting anti-KS activity and then examined for features of apoptosis. Levels of proteins associated with apoptosis were monitored by western blot analysis, and cell DNA content was assessed by flow cytometry. Tumors induced in mice by inoculation of KS Y-1 cells were treated with preparations of hCG, and the tumors were examined for cell morphology and also for DNA fragmentation by use of the terminal deoxynucleotidyl transferase-mediated digoxigenin-deoxyuridine triphosphate nick-end-labeling (TUNEL) assay. RESULTS: The HAF present in some preparations of hCG and in urine fractions has the ability to induce apoptosis in KS cells in vitro and in vivo. HAF-triggered apoptosis was preceded by increased levels of the apoptosis-related proteins c-Myc and c-Rel and cell accumulation in Go/G1 phase of the cell cycle. KS Y-1 cells transfected with a c-Myc complementary DNA showed elevated rates of apoptosis. CONCLUSION: The anti-KS activity of HAF appears to induce apoptosis. Such activity suggests a role for HAF in pregnancy-related regulation of cell death.

Foot care: focus on the elderly.

Problems in the foot develop as a result of the aging process or systemic disease. Common causes of pain and disability in the elderly are nail and skin problems, predominantly corns and calluses, along with circulatory and structural problems. Because patients with orthopaedic conditions may have preexisting foot problems, it is important for nurses to distinguish between minor foot problems that can easily be treated and more serious conditions that require referral to a specialist. This article discusses pathophysiology of the aging foot, a comprehensive foot assessment, common foot problems with nursing interventions, pressure relief and shoewear, and nurses' qualifications for providing foot and nail care.

Relieving intermittent claudication: a nursing approach.

Peripheral arterial disease affects at least 10% of adults older than 70 years. Risk factors such as diabetes, hypertension, hyperlipidemia, history of smoking, and genetics increase the incidence of the disease. Intermittent claudication, experienced as calf pain or cramping, is the primary symptom in patients with lower-extremity peripheral arterial disease. Patients with claudication are unable to walk even moderate distances. As a result, they often lead lives that are profoundly restricted. Medical therapeutic options available for patients with intermittent claudication are limited to a small number of medications and walking exercise rehabilitation. Walking exercise training can significantly increase ability and decrease calf discomfort for many patients. Nurses can have a major impact on improving the quality of life of patients with claudication, not only by seeking referrals to established institutional walking exercise programs, but also by helping patients in the community develop a personalized walking program. In this article, a nursing plan of care including short-term and long-term goals is addressed. A case study will illustrate the effectiveness and improved quality of life that an individualized program of walking exercise had for one community-based client.

The relationship of counseling and self-help participation to patient outcomes in DATOS.

Using a sample of 927 cocaine patients enrolled in programs in three modalities included in the national Drug Abuse Treatment Outcome Studies (DATOS), this investigation examined the relationship of three dimensions of treatment process on after-treatment cocaine and heavy alcohol use and predatory illegal activity. Logistic regression revealed significant reductions in all three outcomes and strong effects of treatment duration and after-treatment self-help, conditional on the modality. Results did not support the hypothesized relationship between treatment outcomes and amounts of counseling and during-treatment self-help. Findings support the robustness of duration effects and after-treatment self-help and contribute to the measurement methodology for calibrating treatment intensity. The strong after-treatment self-help effect in the two residential and inpatient modalities suggests these programs can improve treatment outcomes by making referral to after-treatment self-help participation a standard practice and installing mechanisms to increase the likelihood of attendance at least twice weekly during the year after treatment.

Effects of a urinary factor from women in early pregnancy on HIV-1, SIV and associated disease.

The effects of clinical grade crude preparations of human chorionic gonadotropin (hCG) on Kaposi's sarcoma, HIV, SIV and hematopoiesis were examined in vitro and in vivo. In contrast to previous studies, we report that the antiviral activity of hCG associated factors is not due to the native hCG heterodimer, including its purified subunits or its major degradation product, the beta-core. Using gel permeation chromatography of the clinical grade hCG and urine concentrates from pregnant women, we demonstrate that an as yet unidentified hCG associated factor (HAF) with anti-HIV, anti-SIV, anti-KS and pro-hematopoietic activities elutes as two peaks corresponding to 15-30 kDa and 2-4 kDa.

AIDS-related Kaposi's sarcoma patients with visceral manifestations. Response to human chorionic gonadotropin preparations.

OBJECTIVE: In vitro cell culture studies and a murine model for human Kaposi's sarcoma (KS) have shown that human chorionic gonadotropin (hCG)-associated factor (HAF) isolated from commercial hCG preparations has antiproliferative and cell killing effects on neoplastic KS cells, without toxic effects on normal endothelial cells and lymphocytes. These findings prompted preliminary study of hCG preparations for patients with early-stage KS with skin lesions only and no known visceral involvement. Complete or partial regression of the skin lesions occurred after intralesional injections of hCG (hCG-Pregnyl, hCG-APL). The current study sought to extend these early observations to evaluation of the safety of hCG in acquired immunodeficiency syndrome (AIDS) KS patients with aggressive disease and visceral involvement. These patients present in a more advanced stage of the disease that is coupled with serious immunodeficiency. They commonly respond poorly to conventional chemotherapy and have a reduced median life expectancy of only 4 to 9 months. STUDY DESIGN/METHODS: After approval by the local institutional review boards, 13 patients with advanced AIDS-KS gave informed consent and were treated with hCG preparations. These hCG preparations are known to have antiproliferative activity in laboratory tests. Patients were monitored for tumor size by clinical evaluation, ultrasonography, radiography, respiratory functions, and endoscopic examination. Histologic examinations of biopsied tissues were used for studies of apoptosis using in situ hybridization techniques. The patients were also monitored for CD4+ T-cell numbers and human immunodeficiency virus type 1 (HIV-1) plasma viral load according to common clinical practice. RESULTS: Thirteen patients with advanced AIDS-KS and visceral KS were treated with hCG. Five of 13 (38%) patients had dramatic responses to therapy, and overall tolerance to the drug was excellent for all patients. Some hCG preparations also showed beneficial effects against HIV-associated markers. An accompanying decrease in viral load (plasma HIV-1 RNA) was observed in one patient, a dramatic increase in CD4+ cells occurred in another, and significant weight gain was seen in seven patients. CONCLUSIONS: These clinical observations suggest that patients with aggressive visceral forms of KS, usually indicative of an extremely poor prognosis and poor response to combined chemotherapy, can benefit from this new therapeutic approach. In some patients, these preparations also induce several other beneficial effects, such as weight gain, reduction in HIV-1 RNA load, or increase in the CD4+ T-cell count. Additional controlled clinical trials comparing this new therapeutic option with standard cytotoxic chemotherapy are needed. These trials should be extended to patients with KS not related to HIV-1 infection. Because we showed elsewhere that pure hCG had no effect on KS, identification and subsequent clinical use of the active molecules in hCG preparations is urgently needed.