Adjuvant Therapy For Cancer Patients Research Articles

Chondroitin sulfate-functionalized selenium nanoparticle-induced S-phase cell cycle arrest and apoptosis in HeLa Cells.

This study aimed to evaluate the anti-cervical cancer activity of chondroitin sulfate-functionalized selenium nanoparticles (SeCS) and to elucidate their action mechanism. Cytotoxic effect of SeCS on HeLa cells was assessed by MTT assay. Further molecular mechanism of SeCS was analyzed by flow cytometric assay and western blotting. The results showed that treatment with SeCS resulted in a dose- and time-dependent inhibition in the proliferation of HeLa cells. The data obtained from flow cytometry demonstrated that SeCS inhibited HeLa cell growth via the induction of S-phase arrest and cell apoptosis. Further mechanism analysis found that SeCS down-regulated expression levels of cyclin A and CDK2 and up-regulated p21 expression, which contributed to S arrest. Moreover, SeCS increased the level of Bax and decreased the expression of Bcl-2, resulting in the release of cytochrome C from mitochondria and activating caspase-3/8/9 for caspase-dependent apoptosis. Meanwhile, intracellular reactive oxygen species (ROS) levels were elevated after SeCS treatment, suggesting that ROS might be upstream of SeCS-induced S-phase arrest and cell apoptosis. These data show that SeCS has anti-tumor effects and possesses the potential to become a new therapeutic agent or adjuvant therapy for cancer patients. PRACTICAL APPLICATION: In our previous study, we used chondroitin sulfate to stabilize nano-selenium to obtain SeCS to improve the bioactivity and stability of nano-selenium. We found that it possessed an inhibitory effect on HeLa cells. However, the molecular mechanism remains unclear. This study elucidated the mechanism of SeCS damage to HeLa cells. SeCS has the potential to become a new therapeutic agent or adjuvant therapy for cancer patients.

A PEGylated liposomal formulation of prochlorperazine that limits brain exposure but retains dynamin II activity: A potential adjuvant therapy for cancer patients receiving chemotherapeutic mAbs

Anti-cancer monoclonal antibodies often fail to provide therapeutic benefit in receptor-positive patients due to rapid endocytosis of antibody-bound cell surface receptors. High dose co-administration of prochlorperazine (PCZ) inhibits endocytosis and sensitises tumours to mAbs by inhibiting dynamin II but can also introduce neurological side effects. We examined the potential to use PEGylated liposomal formulations of PCZ (LPCZ) to retain the anti-cancer effects of PCZ, but limit brain uptake. Uncharged liposomes showed complete drug encapsulation and pH-dependent drug release, but cationic liposomes showed limited drug encapsulation and lacked pH-dependent drug release. Uncharged LPCZ showed comparable inhibition of EGFR internalisation to free PCZ in KJD cells. After IV administration to rats, LPCZ reduced the plasma clearance and brain uptake of PCZ compared to IV PCZ. The results suggest that LPCZ may offer some benefit over PCZ as an adjunct therapy in cancer patients receiving mAb treatment.

Ganoderma lucidum spore oil synergistically enhances the function of cyclophosphamide in the prevention of breast cancer metastasis.

Ganoderma lucidum ( G . lucidum ) is a traditional Chinese herbal medicine that has shown potential as an alternative adjuvant therapy for cancer patients. However, the mechanisms and adjuvant therapeutic effects of G . lucidum in cancer treatment remain unclear. In this work, G . lucidum spore oil (GanoOil), a newly developed oily G . lucidum spore extract was used to investigate the mechanisms and adjuvant therapeutic effects of GanoOil in conjunction with the chemotherapeutic drug cyclophosphamide (CTX) for preventing breast cancer metastasis. In the model of lung metastasis, orally administered GanoOil increased the population of CD8 + T cells and interleukin (IL)-6 cytokine levels in mouse blood, whereas also enhancing the activity of natural killer cells in the spleen. Furthermore, the combination of GanoOil and CTX effectively suppressed the lung metastasis of circulating breast cancer cells, alleviated CTX-induced weight loss, and reduced the ratio of lung and spleen weight to body weight in mice. Moreover, high concentrations of GanoOil exhibited no significant toxicity or side effects in both in vitro and in vivo experiments. In conclusion, GanoOil is a safe drug that can enhance immune activity in mice to achieve therapeutic effects on cancer, and can also synergistically inhibit tumor metastasis with CTX.

Ascorbic Acid in Combination with Chemotherapeutic Agents for Cancer

Cancer accounts for nearly one-quarter of deaths in the United States. The life expectancy after standard treatment for these patients is dismal. New treatment modalities should be considered and evaluated. Ascorbic Acid (AA, Vitamin C) is a relatively low cost and safe nutrient even when given at very high doses (intravenous) that could be a very relevant co-adjuvant in cancer treatment. In vitro and in vivo studies have shown benefit of using high dose intravenous vitamin C as adjuvant therapy in cancer patients. There is significant supporting evidence of the benefits of the use vitamin C with chemotherapy.

M1 and M8 homeopathic complex have been use as adjuvant therapy for cancer patients.

Background: Cancers are complex diseases rated among the top 10 causes of death worldwide. The Laboratory of Inflammatory and Neoplastic Cells at Federal University of Parana have been studied the effects of several highly diluted solutions in cell-based models over de the past decade. Among those solutions, M1 and M8 are highly diluted tinctures complex which act as biological response modifiers. Both complexes turned to be promising compounds to use as adjuvant therapy for selected cancer patient. As a private physician, over the last ten years, many cancer patients have been reached our clinic looking forward homeopathic medicines that could be used as complimentary therapy to their standard cancer treatment. The types of cancer, as well the stages of the disease, among those patients were quite heterogeneous. We have followed not only those who have detected the cancer in an early stage, but also people who have been discouraged, once they’ve been told as a patient without therapeutic possibility. 
 Aims: To exchange observations and outcomes in the disease’s natural history of cancer patients who have been treated with M1 and M8 as adjuvant therapy to the standards treatments.
 Methodology: The prescription of the treatment was based on primary situ of the disease as well the standard treatment which was been followed by the patient at the time of the attendance. It varied from one complex alone, three times a day, to the use of both complexes, six times a day.
 Results and discussion: Many cancer patients who were undergoing chemotherapy reported the side effects of that treatment had become mild in comparison to the time they were not using the complexes. Other interesting outcome was the fact that, for some patients who were skipping chemotherapy sessions due to neutropenia, the standard treatment could be followed as planed after start to use M8. Patients who did surgical procedures reported a better healing process, with less scars, when they compared their own evolution to other patients who attend same oncologic facility.
 Conclusion: Although M1 and M8 act as biological response modifiers and their use as adjuvant therapy for cancer patients is a promising approach, the fact that cancer is complex disease, which requires a multiple approach, brings an ethical consideration on use or not use complimentary therapies as adjuvant treatments. Our private practice showed up in the last decade that cancer patients can benefit from the use of those highly diluted complexes, adjuvant to standard treatments as chemotherapy and surgery.

Crosstalk between aldehyde dehydrogenase-1 and chemoresistance in breast cancer: Insights into the role of vitamin D3

AimsAldehyde dehydrogenase-1 (ALDH-1) is considered a signature of breast cancer stem cells and is linked to poor outcomes in breast cancer patients. This study aimed at investigating the effect of vitamin D3 on enhancing the tumor responsiveness to different conventional chemotherapeutic agents, viz., cisplatin, methotrexate, and doxorubicin. Main methodsIn vitro and in vivo experiments were performed using combinations of vitamin D3 and chemotherapeutic agents. Cell cycle analysis and apoptosis assays were performed. Moreover, ALDH-1 expression levels were estimated in cancer cell lines and solid tumors. For solid tumors, tumor volume and histopathological necrotic indices were estimated. Leukocyte presence was also evaluated in tumors using leukocyte common antigen (LCA). Key findingsResults showed a synergistic interaction between vitamin D3 and each of the chemotherapeutic agents on breast cancer cell lines as well as cell cycle arrest at G2/M phase. A decrease in ALDH-1 levels was reported in both breast cancer cells and in tumor tissues. Reductions in tumor volume were also observed in the groups which received the combination therapy. An influence on necrosis rather than apoptosis was also reported, as evidenced by necrotic indices and Bcl-2 expression in tumor sections, respectively. Increased local leukocytes in tumors was also evident, as indicated by increased expression of leukocyte common antigen (LCA). SignificanceOverall, the present study shows that vitamin D3 has an impact on resistance to different chemotherapeutic agents which could be due to the inhibition of ALDH-1, suggesting its use as an adjuvant therapy in cancer patients receiving chemotherapy.

Growth hormone modulates the inflammatory and apoptotic pathways incorporated in fluorouracil-induced oral mucositis in rats

Introduction: Oral mucositis (OM) is a well-known complication of radiotherapy (RT) and chemotherapy (CT) in cancer patients. Although, 5-flourouracil (5-FU) is one of the standard cytotoxic therapies, it is one of the most common causes of OM, which results in delay, dose reduction or treatment discontinuation, thus this intensifies the need for an effective chemoprotective agent. We aimed to investigate the potential chemoprotective effect of growth hormone (GH) on 5-FU-induced OM in rats. Material & Methods: Rats were either exposed to a single 5-FU injection (160 mg/kg ip) and/or treated with GH (1 mg/kg s.c). Oxidative stress, inflammatory and apoptotic markers were assessed. Results: An array of mucosal damage was produced as a result of 5-FU injection, which was evident by histopathology. 5-FU induced a remarkable increase in lipid peroxidation accompanied with a significant depletion of glutathione level. Besides, inflammatory cascades, including NF-κB and IL-6, were elevated significantly. Furthermore, 5-FU stimulated cell death through the significant increase of caspase-3. Interestingly, Pre-treatment with GH markedly ameliorated the deleterious effects of 5-FU through counteracting the oxidative stress and inflammation-mediated apoptosis. In addition, GH rescued the oral mucosal histology following chemotherapy. Conclusions: Our study is the first to demonstrate evidences for the effective chemoprotection provided by GH against 5-FU induced OM along with the underlying mechanisms, which may offer a promising adjuvant therapy for cancer patients.

Evaluation of Ozone Therapy as adjuvant therapy in cancer patients and reduction of side effects of Radiation therapy- Indian experiences [abstract

PURPOSE: India is new cancer capital of world with almost one third of cases registered from India, In this century, cancer is projected to be the leading cause of death. Neoplasia is a multifactorial process that can be broadly categorized into five etiologies: genetic, viral, chemical, physical and inflammatory. Chemical, physical and inflammatory are closely linked to reactive oxygen species (ROS), which can readily induce genomic damage. Although the precise mechanisms responsible for increased ROS stress in cancer cells have not be defined, the increase in ROS generation is attributed to active cellular metabolic activity under the influence of oncogenic signals and/or to mitochondrial malfunction in cancer cells. Ozone therapy (OT) biological effects are: cellular redox balance (OT can exert its protective effects by means of an oxidative preconditioning, stimulating and/or preserving the endogenous antioxidant systems); regulation of the immunological system, increase of prostacyclin, as well as the increase of oxygenation in tumours. Tumour Hypoxia is a well-recognized mechanism for resistance of neoplastic cells to anticancer drugs and radiation.
 
 MATERIAL and METHODS: The clinical trial included only 83 patients with mainly oral, breast and brain cancer patients in treatment with cobalt-60 therapy at Lady Ratan Tata memorial radiation department were also treated with Rectal Insufflation of an ozone-oxygen at a dose of 7mg (200 ml at 35 mcrg/ml), 6 days per week along with Minor auto haemotherapy(100 mcrg) alternatively for 6 weeks till the duration radiotherapy.
 
 RESULTS: The appearance of side effects (dermatitis, pigmentation, ulceration) minimized to 24% in the ozone group that means a significant difference post radiation. When compared to patients not treated with OT. One month after finishing the treatment, with significant difference in patients supported by OT. The clinical observation were:
 - Improvement in Energy Level
 - Feeling of Cheerfulness
 - Improved Appetite
 - Improved WBC, RBC and Hb levels
 - Reduction in Tumor Markers, CEA, AFP, CA125
 
 CONCLUSION: OT is effective as adjuvant to conventional approach of Radiation in reducing side effects of radiation by improvement of blood circulation and oxygen delivery to ischemic and neoplastic tissues. Furthermore, it correct the chronic oxidative stress by upregulating the antioxidant system procuring a state of well-being in patients by activating the neuro-endocrine system.

Transition of the abnormal Savda syndrome to the hepatic carcinoma shifted unfolded protein response to autophagy was partly reversed by Savda Munziq in a rat model

ObjectivesIn Uighur medicine, abnormal Savda Munziq (AMSq) is an adjuvant therapy for cancer patients with abnormal Savda syndrome (ASS) who exhibit the highest degree of pathogenicity and malignancy. The aim of the study was to understand the role(s) of AMSq in cancer patients with ASS. MethodsA total of 125 rats were divided into groups: control (NC) (n = 15), ASS (n = 25), ASS with hepatic carcinoma (ASSHC) (n = 25) as well as ASSHC treated with low dose (ASSHC-L, n = 20), medium dose (ASSHC-M, n = 20) and high dose (ASSHC-H, n = 20) AMSq. Changes in the unfolded protein response (UPR) and autophagy were analyzed by RT profiler PCR array kits, which covered 84 UPR and 84 autophagy related genes. Protein expression analyses of LC3B, ATG8, GRP78 and CHOP were carried out using western blotting. ResultsCHOP and GRP78 expression was enhanced in ASS and ASSHC compared to NC rats and further increased AMSq dose-dependently, indicating an UPR triggering effect of AMSq. The ratios of ATG8/LCB3II-LCB3I protein were reduced in ASSHC rats, an effect which was partly reversed by AMSq. Compared to NC rats in the ASS group, 24 UPR genes were significantly upregulated and 3 downregulated, whereas only 5 autophagy genes were significantly upregulated and 5 downregulated. Compared to NC rats in the ASSHC group, 15 UPR genes were significantly upregulated and 10 downregulated, whereas 16 autophagy genes were significantly upregulated and 8 downregulated. The RT profiler data indicated a shift from UPR in the ASS to the autophagy response in ASSHC rats. ASMq effects on ASSHC rats comprised significant downregulation of 10 autophagy and 2 UPR genes. ConclusionThe transformation into hepatic cancer cells included a shift from endoplasmic reticulum stress-related UPR to autophagy gene activation, an effect which could be partly reversed by ASMq.

Documentation of medical marijuana use in cancer patients.

Medical marijuana is often used as adjuvant therapy in cancer patients for symptom management, although limited evidence-based studies evaluating its efficacy or safety exist. Similar to over-the-counter medications, supplements, or herbal products, documentation of medical marijuana is important to monitor efficacy, potential adverse effects, or interactions. The objective of this quality improvement study was to improve the consistency of medical marijuana documentation in cancer patients by assessing current practices; educating healthcare team members about the importance of documentation and newly established documentation process; and evaluating the new documentation process. This three-part quality improvement study was approved by the Institutional Review Board. In part I, a voluntary survey was sent via email to Cancer Center healthcare personnel to assess the current documentation process of medical marijuana. In part II, a best practice process for documenting medical marijuana in the electronic medical record was established. Medical marijuana was to be listed as a historical medication in the medication list. In-person and electronic education sessions were offered to Cancer Center clinical staff. The education emphasized the importance of documenting medical marijuana use and provided a detailed process for electronic medical record documentation. A pre- and post-test to assess understanding was also included. Part III was a retrospective chart review to evaluate documentation practices of certified medical marijuana users in the Cancer Center. Patients included in the study were greater than 18 years old and certified for medical marijuana use on or after 1 January 2018. Department of Corrections patients were excluded. Descriptive statistics were used for data analysis. The survey results in part I demonstrated a lack of consistency in the documentation of medical marijuana in the Cancer Center. The pre- and post-test scores measured in part II showed a significant improvement in understanding after education was provided. The average pre-test score was a 61 and post-test score was 88, indicating an average increase of 27 points. A larger increase in test scores was observed in those attending the in-person education than the online sessions (p < 0.002). The results of the retrospective chart review in part III revealed 56 patients who met inclusion criteria, but only 39 patients were alive and evaluated at the time of the retrospective chart review. Of the 39 patients, 22 never completed the patient registration process and therefore, would never have been able to obtain medical marijuana. Seven patients had medical marijuana properly documented in their medication list and 10 patients were missing documentation in the medication list, showing room for improvement in documentation practices. This quality improvement study led to the implementation of medical marijuana documentation in the medication list. Education increased healthcare team members understanding of medical marijuana utilization and the importance of documentation.

Protective Role of Fucoidan on Cisplatin-mediated ER Stress in Renal Proximal Tubule Epithelial Cells.

Administration of cisplatin in cancer patients is limited by the kidney-related adverse effects; however, a protective strategy is absent. We hypothesized that fucoidan protects the proximal tubule epithelial (TH-1) cells against the effects of cisplatin. To assess the effect of fucoidan, its effect on reactive oxygen species (ROS) formation, endoplasmic reticulum (ER) stress response, DNA damage response (DDR), apoptosis, and cell-cycle arrest in TH-1 cells was investigated. Cisplatin increased the accumulation of ROS, leading to excessive ER stress. In presence of cisplatin, treatment of TH-1 cells with fucoidan significantly reduced the ER stress by maintaining the complex of GRP78 with PERK and IRE1α. In particular, fucoidan enhanced the antioxidative capacity through up-regulation of PrPC Furthermore, fucoidan suppressed cisplatin-induced apoptosis and cell-cycle arrest, whereas silencing of PRNP blocked these effects of fucoidan. Fucoidan may be a potential adjuvant therapy for cancer patients treated with cisplatin as it preserves renal functionality.

Nerolidol attenuates cyclophosphamide-induced cardiac inflammation, apoptosis and fibrosis in Swiss Albino mice

Incidence and prevalence of cancer is an alarming situation globally. For the treatment of cancer many anticancer drugs have been developed but, unfortunately, their potential cardiotoxic side effects raised serious concerns about their use among clinicians. Cyclophosphamide is a potent anticancer and immunosuppressant drug but its use is limited due to cardiotoxic side effect. Thus, there is a need for the development of certain drug which can reduce cardiotoxicity and can be used as an adjuvant therapy in cancer patients. In this direction we, therefore planned to evaluate nerolidol (NER) for its cardioprotective potential against cyclophosphamide-induced cardiotoxicity in Swiss Albino mice. Animals were divided into 6 groups. Vehicle control; Cyclophosphamide (CP 200); NER 400 per se; NER 200 + CP 200; NER 400 + CP 200; and fenofibrate (FF 80) + CP 200. Dosing was done for 14 days along with a single dose of CP 200 on the 7th day. On 15th day animals were sacrificed and various biochemical parameters pertaining to oxidative stress, nitrative stress, inflammation, apoptosis and fibrosis were estimated in the blood and heart tissues. Histopathological analysis (H & E and Masson's trichrome staining); ultrastructural analysis (transmission electron microscopy) and immunohistochemical analysis were also performed along with mRNA expression and molecular docking to establish the cardioprotective potential of nerolidol. Nerolidol acted as a potent cardioprotective molecule and attenuated CP-induced cardiotoxicity.

Vitamin D Resists Cyclophosphamide-Induced Genomic and DNA Damage in CHL Cells In Vitro and in Mice In Vivo

Vitamin D as an adjuvant therapy for cancer patients is hoped to have a beneficial outcome based on its physiological activity, but clinical trials so far by addition of vitamin D show unremarkable curative improvement, mechanism for explain this phenomena is not well-understood. The aim of this study was to determine whether vitamin D resists cyclophosphamide (CP)-induced genomic and DNA damage. In CHL cells in vitro, 1α,25-(OH)2D3 at 10, 50, and 100 nM was found to alleviate the frequency of chromosomal aberration with an alleviation range of 40.7–44.0%. There was a dose-dependent decrease for a proportion of γ-H2AX foci positive cells in response to an increase in 1α,25-(OH)2D3 concentration. Two vitamin D3 injections of 1,000, 5,000, or 10,000 IU suppressed CP-induced micronucleus formation in mice BMCs with an alleviation range of 36.7–44.5%, mitigated lymphocytes DNA damage reflected by lower tail DNA, tail length and olive tail moment parameter in comet assay. Vitamin D showed an antagonistic effect on CP-induced genomic and DNA damage. Our data suggest that vitamin D as an adjuvant combine antineoplastic drug with genotoxicity administer to tumor patients is contraindicant.

In vitro anticancer effect of tricyclic antidepressant nortriptyline on multiple myeloma.

Drug repurposing has been proved to be an effective strategy to meet the urgent need for novel anticancer agents for multiple myeloma (MM) treatment. In this work, we aimed to investigate the anticancer effect and mechanism of tricyclic antidepressant nortriptyline (NTP) on the U266 MM cell line. The in vitro inhibitory effect of NTP at various doses and time points was studied. The combination potential of cisplatin-NTP was also investigated. Cell cycle analysis and three flow cytometric apoptosis assays were performed. NTP showed dose- and time-dependent inhibitory effects on the U266 MM cell line. NTP had greater inhibitory effect than cisplatin (IC50 26 µM vs. 40 µM). The cisplatin-NTP combination is antagonistic. In addition to G2/M phase cell cycle arrest, NTP induced apoptosis as indicated by mitochondrial membrane potential and caspase-3 and annexin V assays. NTP has inhibitory and apoptotic effects on U266 MM cells. The cisplatin-NTP combination indicated strong antagonism, which may have significant clinical relevance since antidepressants are commonly employed in adjuvant therapy for cancer patients. Based on these findings, the therapeutic potential of NTP for MM treatment should be investigated with in-depth mechanistic studies and in vivo experiments.

Dexamethasone and Fludrocortisone Inhibit Hedgehog Signaling in Embryonic Cells.

The hedgehog (Hh) pathway plays a central role in the development and repair of our bodies. Therefore, dysregulation of the Hh pathway is responsible for many developmental diseases and cancers. Basal cell carcinoma and medulloblastoma have well-established links to the Hh pathway, as well as many other cancers with Hh-dysregulated subtypes. A smoothened (SMO) receptor plays a central role in regulating the Hh signaling in the cells. However, the complexities of the receptor structural mechanism of action and other pathway members make it difficult to find Hh pathway inhibitors efficient in a wide range. Recent crystal structure of SMO with cholesterol indicates that it may be a natural ligand for SMO activation. Structural similarity of fluorinated corticosterone derivatives to cholesterol motivated us to study the effect of dexamethasone, fludrocortisone, and corticosterone on the Hh pathway activity. We identified an inhibitory effect of these three drugs on the Hh pathway using a functional assay in NIH3T3 glioma response element cells. Studies using BODIPY-cyclopamine and 20(S)-hydroxy cholesterol [20(S)-OHC] as competitors for the transmembrane (TM) and extracellular cysteine-rich domain (CRD) binding sites showed a non-competitive effect and suggested an alternative or allosteric binding site for the three drugs. Furthermore, the three steroids showed an additive effect on Hh pathway inhibition when tested in combination with cyclopamine. Our study reports the antagonistic effect of dexamethasone, fludrocortisone, and corticosterone on the Hh pathway using functional assay and confirmed that they do not bind to the CRD or adjacent TM binding cavities of SMO. The study also suggests that dexamethasone could be additionally beneficial as the adjuvant therapy for cancer patients with an established link to the dysregulated Hh pathway.

Ganoderma lucidum Polysaccharides as An Anti-cancer Agent.

The mushroom Ganoderma lucidum (G. lucidum) has been used for centuries in Asian countries to treat various diseases and to promote health and longevity. Clinical studies have shown beneficial effects of G. lucidum as an alternative adjuvant therapy in cancer patients without obvious toxicity. G. lucidum polysaccharides (GLP) is the main bioactive component in the water soluble extracts of this mushroom. Evidence from in vitro and in vivo studies has demonstrated that GLP possesses potential anticancer activity through immunomodulatory, anti-proliferative, pro-apoptotic, anti-metastatic and anti-angiogenic effects. Here, we briefly summarize these anticancer effects of GLP and the underlying mechanisms.

Increase of the antitumour efficacy of the biocompound IMMUNEPOTENT CRP by enzymatic treatment

ABSTRACTIMMUNEPOTENT CRP is a dialyzable leukocyte extract obtained from bovine spleen with immunomodulatory and antitumour properties; therefore, when administrated as an adjuvant therapy for cancer patients, it has increased their survival and quality of life. The bioavailability of any orally administered compound can be reduced due to gastrointestinal enzymes. In this study, we evaluated if IMMUNEPOTENT CRP is resistant to the treatment with different enzymes (proteases, nucleases, polysaccharide-degrading enzymes or lipase), using as parameters for biological activity measurement its in vitro antitumour and antioxidant properties and in vivo the antitumour effect of IMMUNEPOTENT CRP treated with proteinase K. In conclusion, we consider necessary to include the antioxidant and cytotoxic activity on the MCF-7 cancer cell line as parameters for the quantitative determination of biological activity or potency tests for batch release. Additionally, the results showed that different enzymatic treatments do not affect the antitumour and antioxidant activities of IMMUNEPOTENT CRP in vitro, suggesting that this product can be administered orally without any loss of biological activity. Furthermore, IMMUNEPOTENT CRP treatment with proteinase K increases the antitumour activity in vivo.

Feasibility of high-intensity interval training with hyperoxia vs. intermittent hyperoxia and hypoxia in cancer patients undergoing chemotherapy - Study protocol of a randomized controlled trial.

Exercise has been well demonstrated to potentially reduce chemotherapy-induced side effects and possibly aid slowing down tumor growth in cancer patients but exercise training adherence is typically low. Thus, training regimens which are perceived less strenuous but do not compromise the training-induced beneficial adaptations will help to increase adherence to exercise and reduce attrition.This 4-armed study aims to investigate the effects of high intensity interval training (HIIT) in hyperoxia versus intermittent hyperoxia and hypoxia in cancer patients undergoing chemotherapy. Forty-eight cancer patients will be randomized into either of three intervention groups or a no-training control group. Patients in the intervention groups will perform twice weekly HIIT on a cycle ergometer in hyperoxia, intermittent hyperoxia and hypoxia or normoxia. Study outcomes will be assessed before and after 4 weeks of training, while selected measures will also be performed pre- and post the first and last training session. The primary aim of this study is to investigate the feasibility, compliance, tolerance and safety of the training. Secondary endpoints will include measures of quality of life, aerobic capacity, transcutaneous oxygen saturation, red blood cell deformability, as well as the assessment of anabolic and catabolic hormone concentrations, reactive oxygen species, cytokine profiles and NK-cell cytotoxicity.To the best of our knowledge, this is the first study investigating the combined effects of exercise with modified fraction of inspired O2 in cancer patients. As such, we provide a novel approach for exercise as an adjuvant therapy in cancer patients undergoing chemotherapy.

Granulocyte-macrophage colony-stimulating factor increases tumor growth and angiogenesis directly by promoting endothelial cell function and indirectly by enhancing the mobilization and recruitment of proangiogenic granulocytes.

Granulocyte-macrophage colony-stimulating factor has been widely used as an adjuvant therapy for cancer patients exhibiting myelosuppression induced by chemotherapy or radiotherapy. However, the effects of granulocyte-macrophage colony-stimulating factor on tumor growth, as well as its precise mechanism, are still controversial due to inconsistent evidence. This study investigated the effect of exogenous granulocyte-macrophage colony-stimulating factor on the growth of B16 melanoma, S180 sarcoma, and U14 cervical carcinoma in mice. The angiogenesis and recruitment of bone-marrow-derived cells were analyzed in tumor tissues. Interactions among granulocyte-macrophage colony-stimulating factor, bone-marrow-derived cells, and B16 tumor cells were investigated in vitro. Proangiogenic types of bone-marrow-derived cells in blood were assessed both in vivo and in vitro. The results showed that granulocyte-macrophage colony-stimulating factor markedly facilitated the growth of B16 and S180 tumors, but not U14 tumors. Granulocyte-macrophage colony-stimulating factor increased the densities of blood vessels and the number of bone-marrow-derived cells in B16 tumor tissues. The granulocyte-macrophage colony-stimulating factor-induced enhancement of tumor cell proliferation was mediated by bone-marrow-derived cells in vitro. Meanwhile, a distinct synergistic effect on endothelial cell function between granulocyte-macrophage colony-stimulating factor and bone-marrow-derived cells was observed. After separating two types of bone-marrow-derived cells, granulocyte-macrophage colony-stimulating factor-induced enhancement of tumor growth and angiogenesis in vivo was mediated by proangiogenic cells in granulocytes, but not monocytes, with CD11b+, vascular endothelial growth factor receptor 2, and C-X-C chemokine receptor 4 granulocytes possibly involved. These data suggest that granulocyte-macrophage colony-stimulating factor contributes to the growth and angiogenesis of certain types of tumor, and these mechanisms are probably mediated by proangiogenic cells in granulocytes. Applying granulocyte-macrophage colony-stimulating factor may attenuate the antitumor effects of chemotherapy and radiotherapy in certain types of tumor.

Integrin (αvβ3) Targeted RGD Peptide Based Probe for Cancer Optical Imaging.

Integrins have an important impact on the regulation of normal and tumor cell migration and survival, especially the integrin αvβ3 and its role in angiogenesis and tumor metastasis. Owing to the role of integrins, non-invasive imaging of αvβ3 expression in diseased tissue will be of great benefit in directing adjuvant therapy for cancer patients. To this end, RGD peptide based probes for optical imaging have emerged as a real-time, sensitive, and noninvasive approach for visualization, localization, and measurement of cancer in vivo. With the advantages of optical imaging such as sensitivity, cost effectiveness, and non-invasion, the past decades have witnessed the rapid development of integrin- targeted optical probes and its wide applications in cancer research. In this review, we present and introduce numerous approaches by the term "RGD motif based optical imaging probes" with respect to their probe design strategies and applications. Additionally, a variety of labels such as QDs, UCLs and near-infrared fluorochrome used in these optical imaging probes are also discussed.