scholarly journals A Phase-2 Study on the Kinetics of the Improvement in Lymphocyte-toMonocyte Ratio by High-Dose Pineal Hormone Melatonin in Lymphocytopenic Untreatable Metastatic Cancer Patients

2019 ◽  
Vol 2 (1) ◽  
pp. 14-19
Author(s):  
Lissoni Paolo ◽  
◽  
Porro Giorgio ◽  
Cenaj Vezika ◽  
Aymerich Tiziana ◽  
...  
Keyword(s):  
Cancer Patients ◽  
T Lymphocyte ◽  
Metastatic Cancer ◽  
Control Group ◽  
High Dose ◽  
Neoplastic Disease ◽  
Monocyte Count ◽  
Mean Values ◽  
T Lymphocyte Proliferation

It is known that lymphocytopenia is one of the most negative biomarkers in cancer patients, being an expression of cancer-related immunosuppression. Today it is known that, despite its complexity, the antitumor immunity is mainly mediated by dendritic cell-T lymphocyte system and suppressed by the macrophage-regulatory T lymphocyte system. Then, lymphocyte-to-monocyte ratio (LMR) has been proven to represent a more appropriate prognostic clinical index than the simple lyphocytopenia alone. Because of the fundamental role of lymphocytes in mediating tumor cell destruction, the correction of cancer-related lymphocytopenia could influence the clinical history of the neoplastic disease. At present, the only cytokine able to induce a clear in vivo lymphocytosisis IL-2. However, it has been demonstrated that the immune system is physiologically under a neuroendocrine control, and that the pineal hormone MLT may stimulate T lymphocyte proliferation and activation. On these bases, we have evaluated the effect of highdose MLT therapy in metastatic solid tumor patients with persistent lymphocytopenia and abnormally low values of LMR. The study included 14 patients, and the results were compared to those found in a control group of 20 lymphocytopenic untreatable metastatic cancer patients treated with the only best supportive care alone. Patients received MLT at a dose of 100 mg/day orally in the evening for 3 consecutive months. Lymphocyte mean count increases on MLT therapy, and the values observed after two months of therapy were significantly higher than the pretreatment ones, with a normalization of lymphocyte number in 4/14 (29%) patients, whereas no spontaneous lymphocyte rise occurred in the control group. On the other hand, monocyte count rapidly diminished on MLT therapy, and LMR mean values observed after only one month of treatment was significantly higher than that found prior to therapy, whereas it significantly decreases in controls. This preliminary study shows that high-dose MLT may improve the immune status of cancer patients, and be effective in the treatment of disseminated cancer-related lymphocytopenia.

Interleukin-4 Blood Concentrations in Early and Metastatic Human Solid Neoplasms

1997 ◽  
Vol 12 (2) ◽  
pp. 75-78 ◽  
Author(s):  
P. Lissoni ◽  
D. Merlini ◽  
D. Pirato ◽  
S. Meregalli
Keyword(s):  
Cancer Patients ◽  
Interleukin 4 ◽  
Th2 Cells ◽  
Control Group ◽  
Blood Levels ◽  
Neoplastic Disease ◽  
Blood Concentrations ◽  
Mean Values ◽  
Cell Functions ◽  
Th2 Cell

Blood levels of the immunosuppressive cytokines IL-6 and IL-10 are often abnormally high in patients with advanced cancer. However, since IL-6 and IL-10 may be produced by macrophages and TH2 cells, the evidence of abnormally high values of IL-6 and/or IL-10 may reflect hyperactivation either of the macrophage system or of TH2 cell functions. In contrast, IL-4 is almost completely produced by the TH2 lymphocytes. Therefore, evaluation of IL-4 levels could help to differentiate macrophage from TH2 cell hyperactivation. This study was performed to investigate IL-4 serum levels in a group of cancer patients in relation to the stage of disease and to the secretion of other cytokines. The study included 50 patients, 28 of whom showed distant organ metastases. Lung cancer and gastrointestinal cancers were the most frequent neoplasms in our patients. The control group consisted of 60 healthy subjects. IL-4 was measured by the Elisa method. No patient showed high levels of IL-4. No significant differences were seen between controls and cancer patients, nor between metastatic and non-metastatic patients. In addition, no significant differences in IL-4 mean values were found between patients with normal or high levels of IL-6 and IL-10, or between patients with normal or low IL-2 concentrations. This preliminary study seems to exclude cancer-related abnormally high secretion of IL-4. Therefore, the high levels of IL-6 and/or IL-10 often occurring in advanced neoplastic disease would mainly depend on macrophage production.

274 High-dose medroxyprogesterone acetate (MPA) in metastatic cancer patients

1983 ◽  
Vol 19 ◽  
pp. 91
Author(s):  
P. Schmidt-Rhode ◽  
G. Sturm ◽  
K.-D. Schulz ◽  
H.J. Künzig ◽  
M. Wunsch
Keyword(s):  
Cancer Patients ◽  
Medroxyprogesterone Acetate ◽  
Metastatic Cancer ◽  
High Dose

scholarly journals Effect of Synchronous Versus Sequential Regimens on the Pharmacokinetics and Biodistribution of Regorafenib with Irradiation

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 386
Author(s):  
Tung-Hu Tsai ◽  
Yu-Jen Chen ◽  
Li-Ying Wang ◽  
Chen-Hsi Hsieh
Keyword(s):  
Stereotactic Body Radiation Therapy ◽  
In Vivo Studies ◽  
Control Group ◽  
High Dose ◽  
Dependent Manner ◽  
Hep G2 ◽  
Time Curve ◽  
Dose Dependent

This study was performed to evaluate the interaction between conventional or high-dose radiotherapy (RT) and the pharmacokinetics (PK) of regorafenib in concurrent or sequential regimens for the treatment of hepatocellular carcinoma. Concurrent and sequential in vitro and in vivo studies of irradiation and regorafenib were designed. The interactions of RT and regorafenib in vitro were examined in the human hepatoma Huh-7, HA22T and Hep G2 cell lines. The RT–PK phenomenon and biodistribution of regorafenib under RT were confirmed in a free-moving rat model. Regorafenib inhibited the viability of Huh-7 cells in a dose-dependent manner. Apoptosis in Huh-7 cells was enhanced by RT followed by regorafenib treatment. In the concurrent regimen, RT decreased the area under the concentration versus time curve (AUC)regorafenib by 74% (p = 0.001) in the RT2 Gy × 3 fraction (f’x) group and by 69% (p = 0.001) in the RT9 Gy × 3 f’x group. The AUCregorafenib was increased by 182.8% (p = 0.011) in the sequential RT2Gy × 1 f’x group and by 213.2% (p = 0.016) in the sequential RT9Gy × 1 f’x group. Both concurrent regimens, RT2Gy × 3 f’x and RT9Gy × 3 f’x, clearly decreased the biodistribution of regorafenib in the heart, liver, lung, spleen and kidneys, compared to the control (regorafenib × 3 d) group. The concurrent regimens, both RT2Gy × 3 f’x and RT9Gy × 3 f’x, significantly decreased the biodistribution of regorafenib, compared with the control group. The PK of regorafenib can be modulated both by off-target irradiation and stereotactic body radiation therapy (SBRT).

scholarly journals In vivo production of interleukin-5, granulocyte-macrophage colony- stimulating factor, macrophages colony-stimulating factor, and interleukin-6 during intravenous administration of high-dose interleukin-2 in cancer patients [see comments]

Blood ◽  
1991 ◽  
Vol 78 (8) ◽  
pp. 1981-1987 ◽  
Author(s):  
MR Schaafsma ◽  
JH Falkenburg ◽  
JE Landegent ◽  
N Duinkerken ◽  
S Osanto ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Mononuclear Cells ◽  
Bone Marrow Cells ◽  
Interleukin 2 ◽  
Mononuclear Phagocytes ◽  
High Dose ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Stimulating Factor

Abstract Recombinant human interleukin-2 (IL-2), administered to cancer patients by continuous intravenous (IV) infusion (3 x 10(6) U/m2/d), was found to induce the in vivo production of colony-stimulating factors (CSF). Plasma obtained from patients during IL-2 treatment stimulated in vitro colony formation of normal human bone marrow cells, depleted of mononuclear phagocytes and T lymphocytes. This colony-stimulating activity (CSA) was identified as IL-5, granulocyte-macrophage CSF (GM- CSF), and macrophage CSF (M-CSF), by the ability of specific antibodies against these factors to neutralize their effects. The presence of IL-2- induced GM-CSF and M-CSF was also demonstrated by specific radioimmunoassays. During IL-2 treatment, plasma also contained detectable levels of IL-6, which was measured in a bioassay. Using a cDNA-polymerase chain reaction (PCR) with specific primer sets for the various CSF, we showed that IL-2 treatment induced the expression of mRNA for M-CSF, GM-CSF, IL-3, and IL-5, but not for granulocyte CSF (G- CSF) in peripheral blood mononuclear cells, suggesting differential expression of CSF in vivo in response to IL-2. Furthermore, no negative regulators of hematopoiesis, such as interferon gamma (IFN-gamma) or tumor necrosis factor-alpha (TNF-alpha), were found in plasma. These data illustrate that in vivo administration of high-dose IL-2 may result in a stimulatory effect on hematopoiesis. The induction of detectable levels of IL-5 and GM-CSF in the circulation may explain the eosinophilia and neutrophilia observed in these patients.

scholarly journals Visualization of human T lymphocyte-mediated eradication of cancer cells in vivo

2020 ◽  
Vol 117 (37) ◽  
pp. 22910-22919
Author(s):  
Xingkang He ◽  
Xin Yin ◽  
Jing Wu ◽  
Stina L. Wickström ◽  
Yanhong Duo ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Metastatic Cancer ◽  
Car T Cells ◽  
Human T Cell ◽  
Car T ◽  
Metastatic Cancer Cells

Lymphocyte-based immunotherapy has emerged as a breakthrough in cancer therapy for both hematologic and solid malignancies. In a subpopulation of cancer patients, this powerful therapeutic modality converts malignancy to clinically manageable disease. However, the T cell- and chimeric antigen receptor T (CAR-T) cell-mediated antimetastatic activity, especially their impacts on microscopic metastatic lesions, has not yet been investigated. Here we report a living zebrafish model that allows us to visualize the metastatic cancer cell killing effect by tumor- infiltrating lymphocytes (TILs) and CAR-T cells in vivo at the single-cell level. In a freshly isolated primary human melanoma, specific TILs effectively eliminated metastatic cancer cells in the living body. This potent metastasis-eradicating effect was validated using a human lymphoma model with CAR-T cells. Furthermore, cancer-associated fibroblasts protected metastatic cancer cells from T cell-mediated killing. Our data provide an in vivo platform to validate antimetastatic effects by human T cell-mediated immunotherapy. This unique technology may serve as a precision medicine platform for assessing anticancer effects of cellular immunotherapy in vivo before administration to human cancer patients.

scholarly journals Effects of Aerobic Exercise on the Physical Performance and Incidence of Treatment-Related Complications After High-Dose Chemotherapy

Blood ◽  
1997 ◽  
Vol 90 (9) ◽  
pp. 3390-3394 ◽  
Author(s):  
Fernando Dimeo ◽  
Sebastian Fetscher ◽  
Winand Lange ◽  
Roland Mertelsmann ◽  
Joseph Keul
Keyword(s):  
Aerobic Exercise ◽  
Cancer Patients ◽  
Physical Performance ◽  
Randomized Study ◽  
Exercise Program ◽  
Interval Training ◽  
Training Group ◽  
High Dose Chemotherapy ◽  
Control Group ◽  
High Dose

Abstract Loss of physical performance is a universal problem of cancer patients undergoing chemotherapy. We postulated that this impairment can be partially prevented by aerobic exercise. In a randomized study, 33 cancer patients receiving high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (training group, T) performed an exercise program consisting of biking on an ergometer in the supine position after an interval-training pattern for 30 minutes daily during hospitalization. Patients in the control group (C, n = 37) did not train. Maximal physical performance was assessed with a treadmill test by admission and discharge. Physical performance of the two groups was not different on admission. The decrement in performance during hospitalization was 27% greater in the control group than in the training group (P = .05); this resulted in a significantly higher maximal physical performance at discharge in the trained patients (P = .04). Duration of neutropenia (P = .01) and thrombopenia (P = .06), severity of diarrhea (P = .04), severity of pain (P = .01), and duration of hospitalization (P = .03) were reduced in the training group. We conclude that aerobic exercise can be safely carried out immediately after high-dose chemotherapy and can partially prevent loss of physical performance. Based on the potential significance of the observed outcomes, further studies are warranted to confirm our results.

scholarly journals The Chemopreventive Effect of Tanacetum Polycephalum Against LA7-Induced Breast Cancer in Rats and the Apoptotic Effect of a Cytotoxic Sesquiterpene Lactone in MCF7 Cells: A Bioassay-Guided Approach

2015 ◽  
Vol 36 (3) ◽  
pp. 988-1003 ◽  
Author(s):  
Hamed Karimian ◽  
Mehran Fadaeinasab ◽  
Soheil Zorofchian Moghadamtousi ◽  
Maryam Hajrezaei ◽  
Maryam Zahedifard ◽  
...  
Keyword(s):  
Sesquiterpene Lactone ◽  
Histopathological Examination ◽  
Cancer Control ◽  
Control Group ◽  
High Dose ◽  
Mcf7 Cells ◽  
Carcinogenic Effect ◽  
Chemopreventive Effect

Background: Tanacetum polycephalum L. Schultz-Bip is a member of the Asteraceae family. This study evaluated the chemopreventive effect of a T. polycephalum hexane extract (TPHE) using in in vivo and in vitro models. Methods and Results: Five groups of rats: normal control, cancer control, TPHE low dose, TPHE high dose and positive control (tamoxifen) were used for the in vivo study. Histopathological examination showed that TPHE significantly suppressed the carcinogenic effect of LA7 tumour cells. The tumour sections from TPHE-treated rats demonstrated significantly reduced expression of Ki67 and PCNA compared to the cancer control group. Using a bioassay-guided approach, the cytotoxic compound of TPHE was identified as a tricyclic sesquiterpene lactone, namely, 8β- hydroxyl- 4β, 15- dihydrozaluzanin C (HDZC). Signs of early and late apoptosis were observed in MCF7 cells treated with HDZC and were attributed to the mitochondrial intrinsic pathway based on the up-regulation of Bax and the down-regulation of Bcl-2. HDZC induced cell cycle arrest in MCF7 cells and increased the expression of p21 and p27 at the mRNA and protein levels. Conclusion: This results of this study substantiate the anticancer effect of TPHE and highlight the involvement of HDZC as one of the contributing compounds that act by initiating mitochondrial-mediated apoptosis.

scholarly journals INVESTIGATING THE EFFECT OF REFLEXOLOGY IN INTENSITY OF PAIN AND ANXIETY AMONG PATIENTS SUFFERING FROM METASTATIC CANCER IN ADULTS’ HEMATOLOGY WARD

2018 ◽  
Vol 11 (6) ◽  
pp. 401 ◽  
Author(s):  
Simin Jahani ◽  
Fatemeh Salari ◽  
Nasrin Elahi ◽  
Bahman Cheraghian
Keyword(s):  
Cancer Patients ◽  
Metastatic Cancer ◽  
Test Group ◽  
Control Group ◽  
Anxiety Management ◽  
Patients With Cancer ◽  
Significant Difference ◽  
Before And After ◽  
The Mean ◽  
And Control

Objective: Findings suggest dissatisfaction of half of the cancer patients regarding pain and anxiety management. This study aimed to determine the effect of reflexology on the intensity of pain and anxiety among patients with metastatic cancer hospitalized inadulthematology ward.  Methods: In this study, the samples were selected from adult hematology ward in Baghaei 2 hospital in Ahwaz, Iran, according to the inclusion criteria. They were then assigned into treatment and control groups. In the treatment group, reflexology protocol was performed following manual reflexology method by Fr Josef Eugster based on Ingham method on the patient’s bed. In the control group, sole touching was used as the placebo. Reflexology was performed for three days, 30 min per day. Spielberger questionnaire were provided to the samples and completed in the first and third days, and Spielberger questionnaire was provided to the samples and completed. The data obtained from this study were then analyzed by SPSS 20.Results: The two groups did not show a significant difference in terms of demographic characteristics (p>0.05). Based on the obtained results, it was found that in the test group, there was a significant difference between the mean intensity of pain before and after the treatment across all 3 days as well as the mean anxiety of the 1st and 3rd days (p<0.05). However, in the control group, there was no significant difference in terms of mean pain intensity before and after the treatment across 3 days (p>0.05). No significant difference was observed between the mean anxiety of the 1st and 3rd days either (p>0.05).Conclusion: Considering the findings of this research, it can be concluded that reflexology has a positive effect on mitigating the intensity of pain and anxiety in metastatic cancer patients. Therefore, it is recommended that nurses employed in cancer centers benefit from the findings of this research to further help patients with cancer. It is also suggested that further research be conducted on the effect of reflexology on the pain and anxiety of other patients.

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