Potential In Cancer Patients Research Articles

Unacylated Ghrelin Protects Against Muscle Wasting, Mitochondrial Dysfunction, and Neuromuscular Junction Disruption in Tumor Bearing Mice

Background: Cancer cachexia is a complex metabolic syndrome that severely impacts mobility, treatment strategies, and life quality of the patients. However, no treatments are available to mitigate the debilitating consequences of cancer cachexia. Ghrelin is a hormone released from the stomach that increases appetite upon acylation by binding to GHSR1a receptors in the brain. Because of its orexigenic effects and increases in body weight, ghrelin GHSR1a receptor analogs were tested as clinical trials to mitigate muscle wasting and loss of strength in cancer patients in several countries. The analogs (i.e., Anamorelin) increased body weight of the non-small lung cancer patients in European countries and Japan, but failed to increase strength, which is the critical component in cancer cachexia. Mainly due to the lack of improvement in strength and patients’ quality of life, Anamorelin was not approved for clinical use in Europe. While the lack of increases in strength is, at least in part, associated with the adipogenic effects of acylated ghrelin, unacylated ghrelin directly improves satellite cell renewal, muscle growth, and mitochondrial function independent of GHSR1a receptor activation and increases in appetite. Unacylated ghrelin is the predominant population in circulation comprising proximately 90-95% of total ghrelin in humans and rodents. Hypothesis: Unacylated ghrelin projects against muscle wasting, loss of strength, and metabolic dysfunction of tumor bearing mice. Methods and Results: Supplementing the cancer cell conditioned medium (CM) with unacylated ghrelin preserved myotube size. Unacylated ghrelin also diminished the cancer cell CM-induced upregulation of MuRF-1, muscle specific ubiquitin ligase. Interestingly, unacylated ghrelin normalized transcriptional upregulation of denervation markers (i.e., sarcolipin, Runx1, GADD45a) in myotubes treated with CM. To further investigate the therapeutic effects of unacylated ghrelin in vivo, we inoculated lung cancer cell line (LL2, ATCC®) in the flank of 4 months old male mice. Two weeks after the injection prior to development of cachexia, mice were provided with unacylated ghrelin containing drinking water or untreated water as control. Tumor bearing (TB) mice treated with unacylated ghrelin showed 30-40% increases in gastrocnemius and quadriceps weights, while soleus muscle mass was unchanged. In addition to the muscle quantity, unacylated ghrelin increased force generating capacity was also improved by unacylated ghrelin. Notably, unacylated ghrelin increased mitochondrial oxygen consumption rate and protected against neuromuscular junction disruption and denervation in TB control mice. Conclusion: Unacylated ghrelin protects against cancer cachexia by targeting multiple risk factors in skeletal muscle wasting, including protein balance, metabolic alterations, and neuromuscular junction disruption. Our findings show protective effects of unacylated ghrelin against cachexia and neuromuscular impairment in tumor bearing mice, indicating its therapeutic potential in cancer patients. NIA R00 064143 to Ahn B. Pilot funds from the Center for Redox Biology in Medicine, and Cancer Genetics and Metabolism program at the Wake Forest Baptist Comprehensive Cancer Center. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Study of Metallothionein Levels in the Serum of Patients with Malignant Tumour

Metallothionein (MT) is a low molecular weight intracellular protein, the primary function of which is to maintain the homeostasis of heavy metals in living organisms. Only a few research has been carried on the topic molecular mechanism of MT. Recent research points to its significant relationship to carcinogenesis, spontaneous mutagenesis, and the effectiveness of antitumor drugs. Increased level of MT is studied as a potential indicator of increased metabolic activity in cancer. Electrochemical methods are a suitable analytical tool for MT detection. Temperature-denatured blood serum samples of patients diagnosed with cancer were studied using electrochemical analysis (Brdička's reaction). The obtained voltammograms were evaluated as the area under the curve (AUC response). To compare normal and abnormal MT levels, control serum of healthy probands (n = 38) with an average MT amount of 2.2 µg L–1, median 2.1 µg L–1 was used. In all evaluated blood serum samples of cancer patients (n = 228), the average amount of MT was 22.7 µg L–1, and the median was 18.1 µg L–1. The difference (10-fold) between groups was highly statistically significant. The data obtained from the pilot experiment suggest that the levels of thiol compounds such as MT may have clinical potential in cancer patients.

Association of Fibrinolytic Potential and Risk of Mortality in Cancer Patients.

Cancer is a leading cause of death, and the fibrinolytic system shows cooperative effects that facilitate the growth of tumors and the appearance of metastases. This prospective study aimed to evaluate the fibrinolytic potential in cancer patients and its association with mortality outcomes using the fluorometric method of simultaneous thrombin and plasmin generation. The study included 323 cancer patients and 148 healthy individuals. During the 12-month follow-up, 68 patients died. Compared to the control group, cancer patients showed alterations in thrombin production consistent with a hypercoagulability profile, and an increase in plasmin generation. Mortality risk was associated with two parameters of thrombin in both univariate and multivariable analysis: maximum amplitude (Wald 11.78, p < 0.001) and area under the curve (Wald 8.0, p < 0.005), while such associations were not observed for plasmin. In conclusion, this was the first study able to demonstrate the simultaneous evaluation of thrombin and plasmin generation in newly diagnosed untreated cancer patients. Patients with cancer have been observed to exhibit a hypercoagulable profile. During the study, two parameters linked to thrombin generation, MA and AUC, were identified and found to have a potential association with mortality risk. However, no associations were found with parameters related to plasmin generation.

Psychophysiological restorative potential in cancer patients by virtual reality (VR)-based perception of natural environment.

The positive significance of nature to human’ self-reported well-being has been widely confirmed, but less attention has been paid to the study of cancer patients, as well as the role of time on the restorative effects. Therefore, using virtual reality (VR) and the inclusion of patients with esophageal and gastrointestinal cancer as participants, this study conducted indoor experiments to explore patients’ psychophysiological recovery through the perception of five different environmental types with three to five interventions per week. There were 63 participants selected from the People’s Hospital in Shaanxi Province. Depending on their psychophysiological state, they would participate in three to five interventions in a week to compare the number of interventions needed to achieve maximum restoration. The five environmental types utilized varied in land cover, vegetation structure, and landscape characteristics, and were identified as blue space (BS), open green space (OGS), semi-open green space (SOS), closed green space (CGS), and gray space (GrS). Before and after viewing landscapes, the changes of psychophysiological indicators were measured to explore the influence of different environmental types on participants. The results showed that the participants preferred and received the highest perceived restorative potentials in BS and lastly, GrS. The green and blue spaces measurably increased positive emotions and perceived restoration while a decreasing negative emotions and the heart rate (HR) compared with the GrS. Participants had the highest level of relaxation while their eyes were closed in the EEG baseline stage. Moreover, participants received the most relaxation when they contacted with nature three times a week, which indicated that excessive natural participation may not be conducive to the sustained development of cancer patients’ psychophysiological health. Instead of field appreciation, VR could be utilized to increase the access of cancer patients to nature and then be used as an approach to landscape interaction.

Changes in the Dietary Inflammatory Index Over Time and Cancer Development Within Rural Post-Menopausal Women

Abstract Objectives The objective of this study was to determine the extent to which diets with a higher inflammatory potential, as measured by the Dietary Inflammatory Index (DII), are associated with cancer development in a cohort of rural post-menopausal women. Methods This study was a secondary analysis of participants of a randomized control trial evaluating the effect of vitamin D and calcium supplementation on cancer development in rural, post-menopausal women in Nebraska. From this cohort, diets were evaluated via a 2005 Block Food Frequency Questionnaire (FFQ) at baseline and four years later (Visit 9). DII scores were calculated at both time points for each participant, including an unadjusted and energy-adjusted DII score. The relationship with DII scores and cancer development were evaluated using a chi-squared test and logistic regression, controlling for pertinent confounders. The difference in DII scores at baseline and Visit 9 for participants who developed cancer and non-cancer participants was examined via a repeated measure ANOVA test. Results There were 1977 participants with baseline and Visit 9 DII scores available for analysis. There was a significant difference in DII scores between baseline and Visit 9, with a significantly larger change in DII scores in the participants who developed cancer (p = 0.0194), shifting to higher pro-inflammatory scores at Visit 9. Cancer status was not associated with baseline DII scores, nor was DII score a predictor of cancer status, when controlling for confounders. Conclusions These findings illustrate how dietary patterns in persons diagnosed with cancer had significant changes over time, increasing inflammatory diet potential. This increase in inflammatory potential in cancer patients may impact outcomes like treatment success, overall survival, and cancer recurrence, creating a need for more research to further analyze the impact of cancer diagnoses on diet changes, and if these changes are detrimental to cancer survivor outcomes. Funding Sources None.

Biomodulina T partially restores immunosenescent CD4 and CD8 T cell compartments in the elderly.

The changes that occur in the immune system with aging are commonly termed immunosenescence. Immunosenescence affects almost all components and functions of the immune response. The most commonly described change is a decrease in numbers and proportions of naïve T cells combined with the increase of terminally differentiated T lymphocytes, mainly affecting CD8+ T cells. The changes in the naïve T cell compartment are principally attributed to thymic involution and lifelong chronic antigen stimulation, among other triggers. Several strategies such as hormonal products, thymic peptides, or cytokines have been proposed for the restoration of the immune system. Here we show the effects of Biomodulina T (BT) on several populations of the immune system when administered to elderly patients diagnosed with recurrent respiratory infections. BT is a polypeptide fraction of bovine thymus, a Cuban product that obtained sanitary registration in 1994 for its immunomodulatory effects. We found that CD4+ naïve T, CD8+ stem cell-like memory (SCM) T, CD4+ recent thymic emigrants (RTE) T and CD4+ CD31+ naïve T cells increased with the administration of BT, whereas CD4+ and CD8+ T cells expressing PD1 decreased after the treatment with BT. Additionally, the proliferative capacity of CD4+ T cells measured by Ki67 expression, and the CD4+ T cell ability to produce IFN-γ were also improved by BT. Moreover, BT did not increase CD4+ Tregs. Altogether, these findings suggest that BT administration is a promising strategy for immune restoration in elderly patients and improvement of immunotherapeutic potential in cancer patients.

Plasma lncRNA expression profile as a prognostic tool in BRAF-mutant metastatic melanoma patients treated with BRAF inhibitor.

Long non-coding RNAs (lncRNA) are dysregulated in many cancer types. Abnormal baseline levels of these lncRNAs display diagnostic and prognostic potential in cancer patients. The aim of this study was to evaluate the prognostic value of plasma lncRNAs in BRAF-mutant advanced melanoma patients treated with a BRAF inhibitor. Total RNA was isolated from plasma samples collected from 58 advanced BRAF-mutant melanoma patients and 15 healthy donors. The expression levels of 90 lncRNAs were estimated using the LncProfiler qPCR Array Kit (SBI) and LightCycler 96 (Roche). LncRNA expression levels correlated with responses to the BRAF inhibitor (vemurafenib) treatment. The patients were stratified into three groups based on their lncRNA levels with various lncRNA expressions (low, medium, and high). A Cox proportional hazards regression model was used to determine the lncRNAs that were significantly associated with both progression-free and overall survivals (PFS and OS, respectively) in patients receiving vemurafenib. The expression level of 12 lncRNAs was down-regulated, while five lncRNAs were up-regulated in melanoma patients compared to healthy donors. Kaplan-Meier analysis showed that upregulation or downregulation of 11 and 16 different lncRNAs were associated with longer median PFS and OS, respectively. Further analysis demonstrated that the baseline lncRNAs for IGF2AS, anti-Peg11, MEG3, Zeb2NAT are independent prognostic factors in BRAF-mutant advanced melanoma patients treated with vemurafenib. Evaluation of plasma lncRNAs expression level for advanced melanoma diagnosis and prognosis evaluation appears to be a safe and valuable method; however, this method requires further validation in larger cohorts and randomized trials.

THE LEGAL ASPECTS OF FERTILITY IN A PRACTICAL GYNECOLOGICAL ONC

Annually in Russia about 30 000 cases of oncological diseases in young women are diagnosed. The diagnosis of reproductive problems associated with treatment is still little discussed, although the practical recommendations of many professional organizations, including the American Society of Clinical Oncology, underscore the need for mandatory oncologist review of options for maintaining the patient’s fertility. The article analyzes the medical organization when detected in a female patient of childbearing age cancer is to use therapies aimed at subsequent implementation by the patient of her reproductive rights. It is noted that such opportunities are limited to current law, giving the right to persons with cancer at the expense of budget funds to use the methods of assisted reproduction and cryoconservation technologies for maintaining reproductive potential in cancer patients. The article presents evidence of the urgency of introducing changes to the orders of the Ministry of Health of Russia that limit the use of methods of assisted reproductive technologies for cancer patients at the expense of the budget.

121 - The Use of Dobutamine Echocardiography for Recovery Prediction in Cancer Patients with Newly Diagnosed Left Ventricular Dysfunction

Introduction: Myocardial viability is dependent on imaging evidence of myocardial functional reversibility. A variety of imaging modalities can analyze tissue viability and are used as a method to predict tissue recovery in patients with heart failure, but there is limited data and agreement on which modality is a better predictor of viability and recovery potential in cancer patients with newly diagnosed left ventricular systolic dysfunction (LVSD). Our previous analysis has demonstrated lower mortality outcomes in cancer patients with full recovery of LV systolic function. We predict that dobutamine stress echocardiography will be a measure viability and functional recovery potential in patients with new LVSD. Methods: We performed a prospective case assessment on cancer patients with new LVSD (LVEF < 50%). Based on inclusion and exclusion criteria, a total of 26 subjects were enrolled. The patients underwent dobutamine echocardiogram (intravenous doses 2.5 mcg, 5 mcg, 10 mcg) to evaluate dobutamine response. Complete recovery was defined as an increase in left ventricular ejection fraction (LVEF) of more than 10 absolute percent points and achieving an LVEF of more or equal to 50%. Partial recovery was defined as an increase in 10 absolute percent points but not achieving at least an LVEF of 50%. No recovery was defined as lack of increase in LVEF or an increase lower than 10 absolute percent points. Data was analyzed to assess the ability of dobutamine echocardiography in predicting recovery of LV systolic function. Results: Out of twenty-six patients, 19 patients (mean age 58 (19 - 85) years, 12 female) had echocardiographic evidence of augmentation with dobutamine (p-value 0.28). Twenty-six percent (n = 5) of these patient's showed full recovery. Twenty-six percent (n = 5) had a partial response and 48% (n = 9) showed no recovery. Seven patients (mean age 62 years, 7 female) had no echocardiographic evidence of augmentation with dobutamine. Of these 7 patients, none showed full recovery, 43% (n = 3) showed partial recovery and 57% (n = 4) showed no recover. Conclusions: The major finding from our small cohort of patients revealed that in cancer patients with new LVSD and lack of augmentation with dobutamine may suggest a dismal opportunity for complete LV systolic function recovery. Our sample size is a significant limitation to show the potential predictive capability that this technique may have. Larger studies are needed to examine the potential of dobutamine echocardiography in predicting functional recovery and outcomes in this population.

Exercise and Nutrition Prehabilitation for the Evaluation of Risk and Therapeutic Potential in Cancer Patients: A Review.

People with cancer are often faced with multimodal treatment including surgery and medical cancer treatment such as neoadjuvant or adjuvant chemotherapy, combination chemoradiotherapy, and/or immunotherapy. Cancer is associated with cachexia, which influences the perioperative outcome, increasing th

Maintaining the reproductive potential of cancer patients during cancer treatment.

Cancer therapies are known to alter the reproductive potential in cancer patients. Due to improved survival rates in cancer patients of reproductive age, considerations of the long-term effects of cancer therapy have become more significant. Oncofertility is a new discipline in medicine that deals with maintaining the reproductive potential of cancer patients while they are receiving gonadotoxic cancer treatment. The purpose of this review is to explore how cancer treatment impairs reproductive functioning and present the current options for preservation of fertility in women. All patients with reproductive potential should be made aware of the possible treatment-related infertility and be offered appropriate fertility preservation options before cancer treatment is instituted. The hope is that, in the future, mechanism(s) can be developed to preserve immature germ cells in the ovary, so that they can be used for fertilization in vivo or in vitro.

Prognostic Value of CD109+ Circulating Endothelial Cells in Recurrent Glioblastomas Treated with Bevacizumab and Irinotecan

BackgroundRecent data suggest that circulating endothelial and progenitor cells (CECs and CEPs, respectively) may have predictive potential in cancer patients treated with bevacizumab, the antibody recognizing vascular endothelial growth factor (VEGF). Here we report on CECs and CEPs investigated in 68 patients affected by recurrent glioblastoma (rGBM) treated with bevacizumab and irinotecan and two Independent Datasets of rGBM patients respectively treated with bevacizumab alone (n=32, independent dataset A: IDA) and classical antiblastic chemotherapy (n=14, independent dataset B: IDB).MethodsrGBM patients with KPS ≥50 were treated until progression, as defined by MRI with RANO criteria. CECs expressing CD109, a marker of tumor endothelial cells, as well as other CEC and CEP subtypes, were investigated by six-color flow cytometry.ResultsA baseline count of CD109+ CEC higher than 41.1/ml (1st quartile) was associated with increased progression free survival (PFS; 20 versus 9 weeks, P=0.008) and overall survival (OS; 32 versus 23 weeks, P=0.03). Longer PFS (25 versus 8 weeks, P=0.02) and OS (27 versus 17 weeks, P=0.03) were also confirmed in IDA with CD109+ CECs higher than 41.1/ml but not in IDB. Patients treated with bevacizumab with or without irinotecan that were free from MRI progression after two months of treatment had significant decrease of CD109+ CECs: median PFS was 19 weeks; median OS 29 weeks. The presence of two non-contiguous lesions (distant disease) at baseline was an independent predictor of shorter PFS and OS (P<0.001).ConclusionsData encourage further studies on the predictive potential of CD109+ CECs in GBM patients treated with bevacizumab.

Evaluation of Mena isoforms as a surrogate for epithelial mesenchymal transformation and erlotinib resistance in breast carcinoma

1078 Background: Epithelial to mesenchymal transition (EMT) is an important step in invasiveness and has been shown to correlate with metastatic potential in several cancer cell lines, including breast carcinoma. However, given the heterogeneity of tumors in vivo, EMT has not been a reliable marker of metastatic potential in cancer patients. Mena, a member of the enabled (ena)/vasodilator-stimulated phophoprotein (VASP) family, which controls cell motility, is upregulated in the invasive subpopulation of breast cancer cells. Mena is alternatively spliced to include one of four exons: +, ++, invasive (INV), or 11a. In the presence of MenaINV, tumor cells are able to invade even at epidermal growth factor (EGF) concentrations that would otherwise be undetectable by the tumor cells. Currently, there are several clinical and genetic characteristics which can predict sensitivity to erlotinib, an EGF receptor inhibitor, but further studies are necessary. Methods: The animal models used were the polyoma middle T antigen (PyMT) transgenic mouse and severe combined immunodeficiency (SCID) xenografted tumors derived from injection with a human breast carcinoma line, MDA-MB-231, and a rat adenocarcinoma line, MTLn3, with forced expression of MenaINV and Mena11a. Invasive cells and average primary tumor cells were collected using the in vivo invasion assay and Fluorescence activated cell sorting (FACS), respectively, and imaged via immunofluorescence. Results: We show that in both the PyMT and MDA-MB-231 animal models, invasive cells are significantly more mesenchymal than average primary tumor cells, indicating they have undergone EMT. The MTLn3-MenaINV cells are more mesenchymal-like, whereas the Mena11a are more epithelial-like. We also expect that cells with a high Mena INV/11a ratio invade despite the presence of erlotinib. No significant financial relationships to disclose.

Interleukin-12: Biological Properties and Clinical Application

Interleukin-12 (IL-12) is a heterodimeric protein, first recovered from EBV-transformed B cell lines. It is a multifunctional cytokine, the properties of which bridge innate and adaptive immunity, acting as a key regulator of cell-mediated immune responses through the induction of T helper 1 differentiation. By promoting IFN-gamma production, proliferation, and cytolytic activity of natural killer and T cells, IL-12 induces cellular immunity. In addition, IL-12 induces an antiangiogenic program mediated by IFN-gamma-inducible genes and by lymphocyte-endothelial cell cross-talk. The immunomodulating and antiangiogenic functions of IL-12 have provided the rationale for exploiting this cytokine as an anticancer agent. In contrast with the significant antitumor and antimetastatic activity of IL-12, documented in several preclinical studies, clinical trials with IL-12, used as a single agent, or as a vaccine adjuvant, have shown limited efficacy in most instances. More effective application of this cytokine, and of newly identified IL-12 family members (IL-23 and IL-27), should be evaluated as therapeutic agents with considerable potential in cancer patients.

Epigenetic drugs as pleiotropic agents in cancer treatment: Biomolecular aspects and clinical applications

In the last three decades huge efforts have been made to characterize genetic defects responsible for cancer development and progression, leading to the comprehensive identification of distinct cellular pathways affected by the alteration of specific genes. Despite the undoubtable role of genetic mechanisms in triggering neoplastic cell transformation, epigenetic modifications (i.e., heritable changes of gene expression that do not derive from alterations of the nucleotide sequence of DNA) are rapidly emerging as frequent alterations that often occur in the early phases of tumorigenesis and that play an important role in tumor development and progression. Epigenetic alterations, such as modifications in DNA methylation patterns and post-translational modifications of histone tails, behave extremely different from genetic modifications, being readily revertable by "epigenetic drugs" such as inhibitors of DNA methyl transferases and inhibitors of histone deacetylases. Since epigenetic alterations in cancer cells affect virtually all cellular pathways that have been associated to tumorigenesis, it is not surprising that epigenetic drugs display pleiotropic activities, being able to concomitantly restore the defective expression of genes involved in cell cycle control, apoptosis, cell signaling, tumor cell invasion and metastasis, angiogenesis and immune recognition. Prompted by this emerging clinical relevance of epigenetic drugs, this review will focus on the large amount of available data, deriving both from in vitro experimentations and in vivo pre-clinical and clinical studies, which clearly indicate epigenetic drugs as effective modifiers of cancer phenotype and as positive regulators of tumor cell biology with a relevant therapeutic potential in cancer patients.

Compliance and Coping Potential of Cancer Patients Treated in Liaison-Consultation Psychiatry

To investigate the impact of psychiatric illness, aggression, and other covarying variables on the compliance and coping potential of cancer patients treated in liaison-consultation psychiatry. The study involves 270 cancer patients who were admitted to the oncology ward for diagnosis and treatment. Each patient took part in a psychiatric consultation. We used the Transplant Evaluation Rating Scale (TERS), which provides a system for differentially recording the patient's compliance and coping potential (total score for the TERS items 3-10). Following standardization using the basic psychooncological documentation (PO-BADO), the demographic variables were recorded. We also identified the internal processes which each patient used to deal with the disease using criteria established by Kübler-Ross as well as the phases of cancer experience according to Fawzy. Twenty-three variables were checked for their relationship to the coping and compliance potential. For 13 of these, the Mann-Whitney U-test or Spearmann-Rank correlation calculated exceeded the required Bonferroni-adjusted significance level. The calculation of an ordinal regression model containing these significant single variables showed that the following variables are associated with a lower compliance and coping potential according to their estimate (Beta-value): aggression as the dominant form of dealing internally with cancer (Kübler-Ross), pre-existing DSM IV Axis 1 psychiatric disorders, carcinoma-induced psychiatric disorders, necessity of treatment with neuroleptics and male gender. Acceptance as the dominant form of dealing internally with cancer (Kübler-Ross) is strongly associated with a higher compliance and coping potential. The results show that the compliance and coping potential of oncological in-patients can be comprehensively described by the Transplant Evaluation Rating Scale. The instruments of measurement used in the study are also useful for describing risk factors associated with low levels of compliance and coping potential.

Providing psycho-social support by telephone: what is its potential in cancer patients?

This paper provides an overview of the use of supportive telephone interventions in cancer patients. The small number of studies that have been reported to date have demonstrated that such approaches are feasible and well accepted. Current telephone counselling programmes for cancer patients have utilized both one-to-one and group approaches. Given the promise of telephone interventions to provide assistance to patients who may not otherwise receive psycho-social care because of factors such as geographical isolation, physical limitations, or lack of comfort with face-to-face approaches, further development and evaluation of programmes in this area is critically needed. We identify priorities for future research, including determining the most effective ways to deliver telephone interventions, identifying patient groups in which they are most successful, and evaluating cost-effectiveness.

Induction of cellular immune responses by a murine monoclonal anti‐idiotypic antibody recognizing the 791tgp72 antigen expressed on colorectal, gastric and ovarian human tumours

There is accumulating evidence that cellular rather than antibody responses are more effective for tumour rejection. It is therefore important to screen anti-idiotypic (anti-id) antibodies for their ability to stimulate anti-tumour T-cell responses. The human anti-id monoclonal antibody (MAb) 105AD7 stimulated both delayed-type hypersensitivity (DTH) responses in animals and antigen-specific blastogenesis and IL-2 induction in advanced cancer patients. It may not be necessary to use human anti-id antibodies as murine anti-id antibodies, which elicit DTH responses against immunodominant human T-cell epitopes and may be just as useful in the clinic. We have therefore produced a murine anti-id antibody to the same MAb as was used to generate the human anti-id antibody and screened it for its ability to generate cellular anti-tumour immune responses. Low-dose immunization with the murine anti-id MAb NCRC60, which recognises the paratope of the anti-791Tgp72 MAb 791T/36, induced DTH responses to 791Tgp72-expressing tumour cells but not to antigen-negative cells. DTH responses with no detectable antibody responses were induced with 5 micrograms of anti-id NCRC60 without adjuvant. Addition of either complete Freund's adjuvant or Quil A did not enhance DTH responses. However, when the anti-id NCRC60 was linked to KLH and injected in the presence of Freund's adjuvant anti-anti-id antibodies and anti-791Tgp72 antibodies were induced. NCRC60 anti-id was also capable in vitro of priming human T cells from cancer patients to proliferate in response to secondary stimulation with 791Tgp72-expressing tumour cells, suggesting that it may have therapeutic potential in cancer patients.

Short‐term Morphological response of the rat testis to administration of five chemotherapeutic agents

As cancer survival rates improve, there is increasing concern about the adverse effects of chemotherapeutic agents on male fertility. Five chemotherapeutic agents (amethopterin, AP or methotrexate; doxorubicin, DX; cytoxan or cyclophosphamide, CP; cisplatinum, CDDP; and 5-fluorouracil, 5-FU) which belong to three different categories of chemotherapeutic agents (antimetabolite, antibiotic, alkylating agent, alkylating agent, antimetabolite, respectively) were given systemically to adult rats to determine the short-term morphological patterns of response in the testis, and the testes were examined by light microscopy. Morphological patterns of response were found to be highly characteristic for each agent, and some shared morphological responses were evident. All except one chemotherapeutic agent (5-FU) caused spermatogonial damage. Among the defects seen were probable degenerating meiotic spermatocytes (CDDP), presence of micronuclei (DX), "arrested" spermatid development (5-FU), and abnormally shaped step 15 spermatids (5-FU). Damage that could be due to the effect of an agent on the Sertoli cell was failure of sperm release (5-FU, CDDP, DX, and AP), increase in the Sertoli cell lipid (5-FU), and malorientation of step 8 spermatids (5-FU, DX). The varied patterns of damage observed are a possible explanation of why the reproductive recovery potential in cancer patients undergoing chemotherapy is variable and drug-specific.