Bletilla striata polysaccharide improves toxic and side effects induced by 5-FU: an untargeted metabolomics study / 中国中药杂志

This study aimed to analyze the effect of Bletilla striata polysaccharide(BSP) on endogenous metabolites in serum of tumor-bearing mice treated with 5-fluorouracil(5-FU) by untargeted metabolomics techniques and explore the mechanism of BSP in alleviating the toxic and side effects induced by 5-FU. Male BALB/C mice were randomly divided into a normal group, a model group, a 5-FU group, and a 5-FU + BSP group, with eight mice in each group. Mouse colon cancer cells(CT26) were transplanted into the mice except for those in the normal group to construct the tumor-bearing mouse model by subcutaneous injection, and 5-FU chemotherapy and BSP treatment were carried out from the second day of modeling. The changes in body weight, diarrhea, and white blood cell count in the peripheral blood were recorded. The mice were sacrificed and sampled when the tumor weight of mice in the model group reached approximately 1 g. TUNEL staining was used to detect the cell apoptosis in the small intestine of each group. The proportions of hematopoietic stem cells and myeloid progenitor cells in bone marrow were measured by flow cytometry. Five serum samples were selected randomly from each group for untargeted metabolomics analysis. The results showed that BSP was not effective in inhibiting colon cancer in mice, but diarrhea, leukopenia, and weight loss caused by 5-FU chemotherapy were significantly improved after BSP intervention. In addition, apoptotic cells decreased in the small intestinal tissues and the percentages of hematopoietic stem cells and myeloid progenitor cells in bone marrow were significantly higher after BSP treatment. Metabolomics results showed that the toxic and side effects of 5-FU resulted in significant decrease in 29 metabolites and significant increase in 22 metabolites in mouse serum. Among them, 19 disordered metabolites showed a return to normal levels in the 5-FU+BSP group. The results of pathway enrichment indicated that metabolic pathways mainly involved pyrimidine metabolism, arachidonic acid metabolism, and steroid hormone biosynthesis. Therefore, BSP may ameliorate the toxic and side effects of 5-FU in the intestinal tract and bone marrow presumably by regulating nucleotide synthesis, inflammatory damage, and hormone production.

Anticarcinogenic activity of methanol extract of Melastoma malabathricum leaves is attributed to the presence of phenolics compounds and the activation of endogenous antioxidant system / Actividad anticancerígena del extracto metanólico de hojas de Melastoma malabathricum atribuida a la presencia de compuestos fenólicos y a la activación del sistema antioxidante endógeno

Melastoma malabathricum (M. malabathricum) extracts have been reported to exert various pharmacological activities including antioxidants, anti-inflammatory and antiproliferative activities. The objective of the present study was to determine the anticarcinogenic activity of its methanol extract (MEMM) against the azoxymethane (AOM)-induced early colon carcinogenesis in rats. Rats were randomly assigned to five groups (n=6) namely normal control, negative control, and treatment (50, 250 or 500 mg/kg of MEMM) groups. Colon tissues were harvested for histopathological analysis and endogenous antioxidant system determination. MEMM was also subjected to HPLC analysis. Findings showed that MEMM significantly (p<0.05) reversed the AOM-induced carcinogenicity by: i) reducing the formation of aberrant crypt foci (ACF) in colon tissues, and; ii) enhancing the endogenous antioxidant activity (catalase, superoxide dismutase and glutathione peroxidase). Moreover, various phenolics has been identified in MEMM. In conclusion, MEMM exerts the in vivo anticarcinogenic activity via the activation of endogenous antioxidant system and synergistic action of phenolics.

Se ha informado que los extractos de Melastoma malabathricum (M. malabathricum) ejercen diversas actividades farmacológicas, incluidas actividades antioxidantes, antiinflamatorias y antiproliferativas. El objetivo del presente estudio fue determinar la actividad anticancerígena de su extracto de metanol (MEMM) contra la carcinogénesis de colon temprana inducida por azoximetano (AOM) en ratas. Las ratas se asignaron al azar a cinco grupos (n=6), a saber, los grupos de control normal, control negativo y tratamiento (50, 250 o 500 mg/kg de MEMM). Tejidos de colon fueron recolectados para análisis histopatológico y determinación del sistema antioxidante endógeno. MEMM también se sometió a análisis de HPLC. Los hallazgos mostraron que MEMM invirtió significativamente (p<0.05) la carcinogenicidad inducida por AOM al: i) reducir la formación de focos de criptas aberrantes (ACF) en los tejidos del colon, y; ii) potenciar la actividad antioxidante endógena (catalasa, superóxido dismutasa y glutatión peroxidasa). Además, se han identificado varios fenólicos en MEMM. En conclusión, MEMM ejerce la actividad anticancerígena in vivo mediante la activación del sistema antioxidante endógeno y la acción sinérgica de los fenólicos.

The possibility of early diagnosis of colorectal cancer through expression of Lncrna UCA1, Lncrna LINC00970, and Wnt genes; an in-vitro study

Colorectal cancer is the 4thcause of cancer death; with considering the growth process of this cancer and the necessity of early diagnosis, the purpose of the research is to state the LncRNA 00970, LncRNA UCAI,and the Wntgene before and after the treatment by 5-Azacytidine epigenetic medicine, to reach the biomarker in the very first steps of colorectal cancer. In this experiment, the human colon cancer cell line (HT29) treated with different concentrations of 5-aza-2'-deoxycytidine (5-aza-dC) was utilized to induce DNA demethylation; Quantitative PCR (qPCR) was used to measure LncRNA UCA1and LncRNA LINC00970 and Wntexpression. There was a significant relationship between the expression of LncRNA 00970, LncRNA UCAI,and the Wntgene and its effects on colorectal (p < 0.05). The Wntgene was treated by 1 and 10 of 5-Azacytidine epigenetic medicine, which then experienced decreases. In LncRNA UCAI and LncRNA00970 in dose 1 micromolar of 5-Azacytidine had decrement and increment of expressionrespectively that explains their efficiency but in treatment by dose 10 mM of this medicine, no significant LncRNA expression difference was detected, 5-azacitidine has a direct impact on its target genes and LncRNAs.Therefore, it can be used in the early diagnosis of colorectal cancer.

Foot drop - an uncommon presentation of FOLFOX toxicity

A quimioterapia com FOLFOX (oxaliplatina, leucovorina e 5-fluorouracilo) é frequentemente utilizada em doentes com cancro colorretal. Os sais de platina são conhecidos por serem uma classe de quimioterápicos que comumente induzem neurotoxicidade periférica. Na toxicidade induzida pela oxaliplatina, os sintomas sensitivos são os mais frequentes. Neste artigo, apresentamos dois casos clínicos de pacientes com adenocarcinoma de cólon, ambos submetidos à quimioterapia com FOLFOX4, e que desenvolveram neurotoxicidade incomum, apresentando pé pendente após o terceiro ciclo de tratamento. Esta manifestação clínica pode ser explicada por dano axonal nos neurônios motores periféricos do nervo peroneal comum (fibular), que fornece inervação motora aos músculos do pé. A paralisia do nervo fibular causa fraqueza súbita nos músculos do pé, que parece ser temporária. Ambos os doentes recuperaram completamente do evento sem necessidade de ajustes no tratamento, nem introdução de medicamentos diferentes. A apresentação de pé pendente como toxicidade da quimioterapia ainda é pouco compreendida. Os casos relatados mostram o pé pendente como uma manifestação grave e incomum de neuropatia induzida por FOLFOX, que pode ser transitória, e não requer necessariamente intervenção específica.

Chemotherapy based on FOLFOX (oxaliplatin, leucovorin, and 5-fluorouracil) regimen is frequently used in colorectal cancer patients. Oxaliplatin and other platinum agents are known to be a class of chemotherapy drugs that commonly induce peripheral neurotoxicity. The most frequent oxaliplatin related neurotoxicity is sensitive symptoms. Here, we present two cases of patients with colon adenocarcinoma, both undergoing chemotherapy with FOLFOX4, who developed uncommon neurotoxicity, presenting with foot drop after the third treatment cycle. Foot drop may be explained by axonal damage of peripheral motor neurons of the common peroneal (fibular) nerve, which provides motor innervation to the foot muscles. Peroneal nerve palsy causes sudden weakness in the muscles of the foot that seems to be temporary. Both patients completely recovered from the event. There was no need for treatment adjustments, neither introduction of different drugs. Foot drop as chemotherapy toxicity is still poorly understood. The reported cases show foot drop as a severe and uncommon manifestation of FOLFOX-induced neuropathy, that might be transitory, and does not necessarily requires specific intervention.

Immune checkpoint inhibitors in the treatment of colorectal cancer: a review of clinical trials / 中华胃肠外科杂志

Colorectal cancer is the third most common cancer in the world. The treatments include surgery, chemotherapy, radiotherapy and targeted therapy. The guidelines of many tumor types have been rewritten with the advent of immune checkpoint inhibitors. There are significant differences in the efficacy of immune checkpoint inhibitors in colorectal cancer according to microsatellite status. Microsatellite instability-high (MSI-H) colorectal cancer has made a breakthrough in immunotherapy, whether in the late-line, first-line, adjuvant or neoadjuvant therapy. The success of KEYNOTE-177 study has changed the guidelines with pembrolizumab becoming a standard treatment in the first-line treatment of MSI-H advanced colorectal cancer. The NICHE study, which used immunotherapy as neoadjuvant treatment of colorectal cancer, has made exciting achievements in MSI-H colorectal cancer. For microsatellite stability (MSS) colorectal cancer, many studies are ongoing, and immunotherapy is still unable to challenge the status of traditional treatment. In this paper, we review the clinical trials related to immune checkpoint inhibitors of colorectal cancer, expecting to provide references for the development of colorectal cancer immunotherapy.

Effect of Jianpi Bushen Sequential Formula on Adjuvant Chemotherapy of Colon Cancer: Study Protocol for a Randomized Controlled Trial / 中国结合医学杂志

BACKGROUND@#The side effects of chemotherapy-induced nausea and vomiting (CINV) and myelosuppression reduce the cancer patients' adherence to chemotherapy. Many Chinese patients choose Chinese medicine (CM) during chemotherapy to reduce side effects; however, the evidence is lacking. The efficacy of a CM herbal treatment protocol, Jianpi Bushen Sequential Formula (, JBSF) will be evaluated on chemotherapy completion rate among patients with colon cancer.@*METHODS@#A multi-center double-blind randomized controlled trial (RCT) will be conducted on 400 patients with colon cancer who will receive 8 cycles of adjuvant chemotherapy with oxaliplatin and capecitabine (CAPEOX). Patients will be randomized 1:1 to receive the JBSF or placebo formula. The primary outcome is the overall chemotherapy completion rate. The secondary outcomes include individual chemotherapy completion rate, 4-cycle completion rate of chemotherapy, time to treatment failure, relative dose intensity and treatment toxicity. Follow-up visits will be scheduled before every and after last chemotherapy.@*DISCUSSION@#This study will provide evidence on whether JBSF can improve the chemotherapy completion rate and reduce side effects among patients with colon cancer. (Trial registration: ClinicalTrials.gov, No. NCT03716518).

Study on intervention effect of Astragali Radix-Curcumae Rhizoma on growth and metastasis of colon cancer in orthotopic transplantation mice model of colon cancer / 中国中药杂志

Astragali Radix-Curcumae Rhizoma is a classic drug pair mainly used for the treatment of digestive tract-related inflammation and tumors, but the ratio is not fixed in clinical practice. In order to study whether the anti-tumor effect of the drug pair is diffe-rent under different ratios, orthotopic transplantation model of colon cancer was established in mice. Then the principal component analysis(PCA) and cluster analysis(CA) were used to explore the effect of different ratios of the drug pair on the tumor growth and metastasis, and select the optimal ratio of Astragali Radix-Curcumae Rhizoma for anti-colon cancer effect. After administration for 15 days, the body weight of colon cancer mice with the tumor removed, the tumor volume and the number of liver metastases were mea-sured; the pathological changes of tumor tissue and liver tissue were observed by HE staining. At the same time, Western blot method was used to detect the protein expression level of tumor growth-related indicators in tumor tissue(Ki67, HBP1, AFP) and tumor metastasis-related indicators in liver tissue(β-catenin, E-cadherin, vimentin, p53) of the tumor-bearing mice. Subsequently, PCA and CA were used to select the optimal ratio of Astragali Radix-Curcumae Rhizoma for anti-colon cancer effect. The experimental results showed that different ratios of Astragali Radix-Curcumae Rhizoma inhibited tumor growth and metastasis to varying degrees. The ratio at 1∶1 of Astragali Radix-Curcumae Rhizoma had the best inhibitory effect on tumor growth, and the 2∶1 ratio group had the best effect on inhibiting liver metastasis and improving weighed loss. Astragali Radix-Curcumae Rhizoma significantly up-regulated the protein expression of HBP1 in tumor tissue of colon cancer mice, and significantly down-regulated the protein expression of Ki67 and AFP in tumor tissue; meanwhile, Astragali Radix-Curcumae Rhizoma significantly up-regulated the protein expression of E-cadherin in liver tissue of colon cancer mice, and significantly reduced the protein expression of β-catenin, vimentin and p53 in liver tissue. PCA results showed that the first three groups in the Astragali Radix-Curcumae Rhizoma compatibility group that were closer to the sham operation group were in the order of 2∶1, 1∶1 and 3∶2, among which the center distance of the 2∶1 group was the shortest from the sham operation group, indicating that the ratio 2∶1 of Astragali Radix-Curcumae Rhizoma had the best intervention effect on colon cancer in mice, consistent with the commonly used clinical proportion. CA results showed that 11 groups of colon cancer mice were classified into 3 categories: Astragali Radix-Curcumae Rhizoma compatibility group, sham operation group and model group, which was consistent with the theory. The results of this study provide a basis for more effective clinical application of Astragali Radix-Curcumae Rhizoma in the treatment of colon cancer, and provide new ideas for the development of classic drug pairs.

Inhibition effect of active fraction from clove on PI3K/Akt/mTOR signaling pathway to induce apoptosis of human colon cancer HCT116 cells / 中国中药杂志

To screen the sensitive cell lines of active fraction from clove(AFC) on human colon cancer cells, investigate the effects of AFC on the cells proliferation and apoptosis as well as PI3 K/Akt/mTOR(phosphoinositide 3-kinase/Akt/mechanistic target of rapamycin) signaling pathways involved, and reveal the mechanism of AFC for inducing apoptosis of human colorectal carcinoma cells. Cell counting kit-8(CCK-8) assay was used to detect the cytotoxic effect of different concentrations of AFC. AFC-induced apoptosis was detected by Hoechst 33258 fluorescence staining and Annexin V-FITC/PI double staining. HCT116 cells were treated with AFC with or without pretreatment with insulin-like growth factor-Ⅰ(IGF-Ⅰ), and then the protein expression levels of caspase-3, caspase-9, poly ADP-ribose polymerase(PARP), PI3 K, p-PI3 K, Akt, p-Akt, mTOR and p-mTOR in PI3 K/Akt/mTOR signaling pathway were detected by Western blot. RESULTS:: showed that the most obvious inhibitory effect of AFC was on human colon cancer HCT116 cells, and the optimal AFC treatment time was 48 hours. After AFC treatment, typical apoptotic features such as nuclear chromatin concentration, nuclear fragmentation and apoptotic bodies appeared in a dose-dependent manner. Annexin V-FITC/PI double staining showed that as compared with the control group, 50 and 100 μg·mL~(-1) AFC groups increased the apoptosis rate of HCT116 cells significantly(P<0.001); AFC activated caspase-9, cleaved caspase-3 and cleaved PARP in a concentration-dependent manner. The protein expression levels of cleaved caspase-3/procaspase-3, cleaved PARP/PARP and caspase-9/β-actin after treatment of AFC(100 μg·mL~(-1)) were significantly different from those in the control group(P<0.001). The relative protein expression of p-PI3 K, p-Akt and p-mTOR decreased in a concentration dependent manner, while Akt and mTOR showed no significant differences among groups. The ratios of p-PI3 K/PI3 K, p-Akt/Akt and p-mTOR/mTOR in the AFC groups(50 and 100 μg·mL~(-1)) were significantly lower than those in the control group(P<0.01). Its combination with IGF-Ⅰ weakened the effect of AFC in inhibiting PI3 K/Akt/mTOR signaling pathway. The ratios of p-Akt/Akt and p-mTOR/mTOR in the AFC+IGF-Ⅰ group were significantly enhanced as compared with the AFC group(P<0.05). Apoptosis-related protein expression levels(cleaved caspase-3 and cleaved PARP) in HCT116 cells treated with AFC+IGF-Ⅰ were also down regulated. As compared with the AFC group, the ratios of cleaved caspase-3/procaspase-3 and cleaved PARP/PARP in the AFC+IGF-Ⅰ group were significantly decreased(P<0.01). In summary, AFC activated caspase-mediated cascades and induced HCT116 cells apoptosis in a dose-dependent manner, which may be associated with the inhibition of the PI3 K/Akt/mTOR signaling pathway.

Curcumin mediates IL-6/STAT3 signaling pathway to repair intestinal mucosal injury induced by 5-FU chemotherapy for colon cancer / 中国中药杂志

This study aims to investigate the potential mechanism of curcumin in mediating interleukin-6(IL-6)/signal transducer and activator of transcription 3(STAT3) signaling pathway to repair intestinal mucosal injury induced by 5-fluorouracil(5-FU) chemotherapy for colon cancer. SD rats were intraperitoneally injected with 60 mg·kg~(-1)·d~(-1) 5-FU for 4 days to establish a model of intestinal mucosal injury. Then the rats were randomly divided into model group(equal volume of normal saline), curcumin low, medium and high dose groups(50, 100, 200 mg·kg~(-1)), and normal SD rats were used as control group(equal volume of normal saline). Each group received gavage administration for 4 consecutive days, and the changes of body weight and feces were recorded every day. After administration, blood was collected from the heart, and jejunum tissues were collected. The levels of serum interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) were detected by ELISA, and at the same time, the concentration of Evans blue(EB) in jejunum was measured. Hematoxylin-eosin(HE) staining was used to observe the pathological state of jejunum, and the length of jejunum villi and the depth of crypt were measured. The positive expression levels of claudin, occludin and ZO-1 were detected by immunohistochemistry. Western blot was used to detect the protein expression of IL-6, p-STAT3, E-cadherin, vimentin and N-cadherin in jejunum tissues. The results showed that, curcumin significantly increased body weight and fecal weight(P<0.05 or P<0.01), decreased fecal score, EB concentration, IL-1β and TNF-α levels(P<0.05 or P<0.01) in rats. In addition, curcumin maintained the integrity of mucosal surface and villi structure of jejunum to a large extent, and reduced pathological changes in a dose-dependent manner. Meanwhile, curcumin could increase the positive expression of occludin, claudin and ZO-1(P<0.05 or P<0.01), repair intestinal barrier function, downregulate the protein expression of IL-6, p-STAT3, vimentin and N-cadherin in jejunum tissues(P<0.05 or P<0.01), and upregulate the protein expression of E-cadherin(P<0.05). Therefore, curcumin could repair the intestinal mucosal injury induced by 5-FU chemotherapy for colon cancer, and the mechanism may be related to the inhibition of IL-6/STAT3 signal and the inhibition of epithelial-mesenchymal transition(EMT) process.

Cytotoxic activity of extract and active fraction of Turbinaria decurrens Bory on colon cancer cell line HCT-116 / Actividad citotóxica del extracto y la fracción activa de Turbinaria decurrens Bory en la línea celular de cáncer de colon HCT-116

Turbinaria deccurrens Bory contains bioactive compound that is beneficial for health. Turbinaria deccurrens Bory is one of many species of brown seaweed that grows in Indonesian marine life and has been known to have cytotoxic activity. The aim of this study is to determine fucoxantin content and the cytotoxic activity of extract and fraction T. decurrens on colon cancer cell lines. Cytotoxic assay of ethanolic extract, n-hexane, ethyl acetate and ethanolic fractions against HCT-116 by MTS assay using Cell Counting Kit-8 (CCK-8). Fucoxantin content in extract and fraction were analyzed using Reversed-Phase High Performance Liquid Chromatography (RP-HPLC) analysis. Extract and fraction of T. decurrens contain fucoxanthin with the highest content of fucoxanthin was in ethyl acetate fraction. CCK-8 assay showed that extract, n-hexane and ethyl acetate fraction inhibited the growth of HCT-116. Brown seaweed Turbinaria decurrens was potential as an anticolon cancer agent.

Turbinaria deccurrens Bory contiene compuestos bioactivos que son beneficiosos para la salud. Turbinaria deccurrens Bory es una de muchas especies de algas pardas que crecen en aguas marinas de Indonesia y se ha estudiado su actividad citotóxica. El objetivo de este estudio fue determinar el contenido de fucoxantina y la actividad citotóxica del extracto y la fracción de T. decurrens en líneas celulares de cáncer de colon. Se llevó a cabo un ensayo citotóxico de extracto etanólico, nhexano, acetato de etilo y fracciones etanólicas contra HCT-116 mediante ensayo MTS utilizando Cell Counting Kit-8 (CCK-8). El contenido de fucoxantina en el extracto y la fracción se analizaron usando cromatografía líquida de alta resolución de fase reversa (RP-HPLC). El extracto y la fracción de T. decurrens contienen fucoxantina conmayor contenido de fucoxantina en la fracción de acetato de etilo. El ensayo CCK-8 mostró que la fracción de extracto, n-hexano y acetato de etilo inhibía el crecimiento de HCT-116. El alga marrón Turbinaria decurrens es un agente potencial contra el cáncer de colon.

Formulation development and evaluation of colon targeted delayed release methotrexate pellets for the treatment of colonic carcinoma

Colonic carcinoma is one of the most common internal malignancies and is the second leading cause of deaths in United States. Methotrexate (MTX) is a drug of choice in the treatment of colon cancer. The aim of the present research work was to develop and characterize colon targeted pellets of MTX for treatment of colonic carcinoma. The product and process parameters were optimized by screening methods. Pellets were prepared by extrusion spheronization using microcrystalline cellulose (MCC) as spheronizing aid and ethyl cellulose (EC) as release retardant in different ratio. Based on the physical appearance, sphericity and % in vitro drug release, batch P17 containing EC: MCC (3:7) was optimized for core pellets. The site specificity was obtained by screening the coating polymers and by coating the core pellets with EudragitS100. The 32 full factorial design was applied in which airflow rate (X1) and coating time (X2) were the independent parameters and physical appearance (Y1) and time taken for 100% drug release (Y2) were selected as the dependent variables. From the results obtained, 6min of coating time and 60cm3/min airflow rate was optimized. The batch B5 showed appropriate physical appearance and % in vitro drug release upto 17hr indicating sustained release property. The ex-vivo studies performed on rat colon indicated a significant relation with the in vitro drug release. The drug release followed Higuchi's model indicating the diffusion pattern of drug release from the matrix of pellets. Thus, the coated pellets can be a good candidate for site specific delivery of MTX to colon by decreasing the gastric irritation and thus to improve bioavailability.

Adenocarcinoma de cólon: tratamento cirúrgico e quimioterápico / Colon adenocarcinoma: surgical and chemotherapic treatment

Introdução: Esta revisão bibliográfica buscou analisar a literatura pertinente à abordagem cirúrgica e clínica do adenocarcinoma de cólon. Métodos: Foram revisados artigos em bases de dados ­ Pudmed, Medscape e UptoDate ­ e excluídos aqueles com pouca relevância clínica ou baixo de grau de evidência. Resultados: O tratamento do adenocarcinoma de cólon visando a cura é baseado na abordagem cirúrgica. Em estádio iniciais (I e II, sem acometimento linfonodal) o tratamento cirúrgico exclusivo é a indicação atual, sendo restrito o tratamento quimioterápico adjuvante para estádios mais avançados ou pacientes estádio II de alto risco. Devem-se individualizar os casos, às vezes recorrendo-se ao tratamento paliativo. Conclusão: A principal abordagem curativa para adenocarcinoma de cólon é cirúrgica, porém pode-se recorrer à terapia adjuvante quando necessário. No momento não parecem haver dados suficientes para formulação de diretriz com tratamento neoadjuvante.

Introduction: This review sought to analyze the literature pertinent to the surgical and clinical approaches to colon adenocarcinoma. Methods: Review of articles from databases ­ Pubmed, Medscape and UptoDate ­ those little clinical relevance or low clinical relevance or low degree of evidence. Results: The curative treatment of the colon adenocarcinoma is based on the surgical approach. In initial stages (I and II, with no lymph node involvement) the exclusive surgical treatment is the current indication, with adjuvant chemotherapy being restricted to more advanced staging or patients with high-risk stage II disease. Cases must be individualized, sometimes relying on palliative treatment. Conclusion: The main curative approach to colon adenocarcinoma is surgical, however, adjuvant therapy can be relied upon when necessary. At the moment, there do not seem to be enough data for the formulation of guidelines for neoadjuvant treatment.

Exosomes promote cetuximab resistance via the PTEN/Akt pathway in colon cancer cells

Cetuximab is widely used in patients with metastatic colon cancer expressing wildtype KRAS. However, acquired drug resistance limits its clinical efficacy. Exosomes are nanosized vesicles secreted by various cell types. Tumor cell-derived exosomes participate in many biological processes, including tumor invasion, metastasis, and drug resistance. In this study, exosomes derived from cetuximab-resistant RKO colon cancer cells induced cetuximab resistance in cetuximab-sensitive Caco-2 cells. Meanwhile, exosomes from RKO and Caco-2 cells showed different levels of phosphatase and tensin homolog (PTEN) and phosphor-Akt. Furthermore, reduced PTEN and increased phosphorylated Akt levels were found in Caco-2 cells after exposure to RKO cell-derived exosomes. Moreover, an Akt inhibitor prevented RKO cell-derived exosome-induced drug resistance in Caco-2 cells. These findings provide novel evidence that exosomes derived from cetuximab-resistant cells could induce cetuximab resistance in cetuximab-sensitive cells, by downregulating PTEN and increasing phosphorylated Akt levels.

The safety and clinical efficacy of recombinant human granulocyte colony stimulating factor injection for colon cancer patients undergoing chemotherapy

Summary Objective: The present study was designed to evaluate safety and efficacy of recombinant human granulocyte colony stimulating factor (G-CSF) injection and whether this regimen could reduce the incidence of adverse events caused by chemotherapy. Method: A total of 100 patients with colon cancer who were treated with chemotherapy in our hospital from January 2011 to December 2014 were randomly divided into two groups, with 50 patients in each group. The patients in the treatment group received G-CSF 24 hours after chemotherapy for consecutive three days; the patients in the control group received the same dose of normal saline. Routine blood tests were performed 7 days and 14 days after chemotherapy. Results: Compared with the control group, the incidences of febrile neutropenia and leukocytopenia in the treatment group were significantly lower (p<0.05). In addition, the incidence of liver dysfunction in the treatment group was lower than that of the control group, without statistical significance. The incidence of myalgia in the treatment was higher than that of the control group without statistical significance. Conclusion: The present study indicated that G-CSF injection after chemotherapy is safe and effective for preventing adverse events in colon cancer patients with chemotherapy.

Efeito da farinha de yacon (Smallanthus sonchifolius) na resposta imunológica intestinal no câncer colorretal / Effect of yacon meal (Smallanthus sonchifolius) on the intestinal immune response in colorectal cancer

Introdução: O câncer colorretal (CC) pode induzir graves complicações clínicas aos portadores dessa neoplasia. A farinha de yacon (FY) (Smallanthus sonchifolius) é rica em fruto-oligossacarídeos (FOS), que são fermentados por bifidobactérias, produzindo efeitos benéficos à saúde intestinal. Seu efeito no CC, entretanto, é ainda desconhecido, sendo o objetivo deste trabalho investigar os efeitos da FY sobre a resposta imunológica de mucosa em animais com CC induzido. Método: Ratos machos Wistar (n=44) foram divididos em grupo S (sem CC e sem FY na dieta), grupo C (com CC e sem FY na dieta), grupo Y (sem CC e com FY na dieta) e grupo CY (com CC e FY na dieta). Durante cinco semanas, os grupos C e CY receberam injeções de 1,2-Dimetilhidrazina para o desenvolvimento do CC, seguidas por duas semanas para formação das lesões neoplá- sicas. Após esse período, os grupos Y e CY consumiram dieta com FY em quantidades suficientes para fornecer 7,5% de FOS por duas semanas e os demais grupos consumiram dieta AIN-93M. Resposta imunológica da mucosa intestinal foi determinada pela dosagem de imunoglobulina A secretória (sIgA) nas fezes pelo método de ELISA. Dados foram avaliados por ANOVA e teste t pareado (p<0,05). Resultados: Após suplementação com FY na dieta, os níveis de sIgA no grupo CY foram superiores aos do grupo S. No grupo CY, os níveis de sIgA aumentaram quando comparados o início e final da intervenção. Conclusão: A FY foi capaz de aumentar os níveis da IgA fecal nos animais com CC.(AU)

Introduction: Colorectal cancer (CC) can induce serious clinical complications in patients with this neoplasm. Yacon flour (YF) (Smallanthus sonchifolius) is rich in fructooligosaccharides (FOS) that are fermented by bifidobacteria producing beneficial effects on intestinal health. Its effect on CC, however, is still unknown, and the objective of this work is to investigate the effects of YF on the immune response of mucosa in animals with induced CC. Methods: Male Wistar rats (n=44) were divided into group S (without CC and without YF in the diet), group C (with CC and without YF in the diet), group Y (without CC and with YF in the diet) And CY group (with CC and YF in the diet). For five weeks, groups C and CY received injections of 1,2-Dimethylhydrazine for the development of CC, followed by two weeks for the formation of neoplastic lesions. After this period, groups Y and CY consumed diet with YF in amounts sufficient to provide 7.5% of FOS for two weeks and the other groups, consumed diet AIN-93M. Immune response of intestinal mucosa was determined by secretory immunoglobulin A (sIgA) dosing in feces by the ELISA method. Data were evaluated by ANOVA and paired t-test (p<0.05). Results: After supplementation with YF in the diet, sIgA levels in the CY group were higher than those in the S group. In the CY group, sIgA levels increased when compared to the beginning and end of the intervention. Conclusion: FY was able to increase faecal IgA levels in animals with CC.(AU)

Beneficio de la quimioterapia adyuvante en pacientes con cáncer de colon: cohorte retrospectiva de un hospital clínico universitario / Benefit of adjuvant 5-fluorouracil based chemotherapy for colon cancer: a retrospective cohort study

Background: Multiple clinical trials have demonstrated the benefits of adjuvant 5-fluorouracil-based chemotherapy for patients with resectable colon cancer (CC), especially in stage III. Aim: To describe the clinical characteristics of a cohort of CC patients treated at a single university hospital in Chile since 2002, and to investigate if chemotherapy had an effect on survival rates. Material and Methods: Review of a tumor registry of the hospital. Medical records of patients with CC treated between 2002 and 2012 were reviewed. Death certificates from the National Identification Service were used to determine mortality. Overall survival was described using the Kaplan-Meier method. A multivariate Cox proportional hazard regression model was also used. Results: A total of 370 patients were treated during the study period (202 in stage II and 168 in stage III). Adjuvant chemotherapy was administered to 22 and 70% of patients in stage II and III respectively. The median follow-up period was 4.6 years. The 5-year survival rate for stage II patients was 79% and there was no benefit observed with adjuvant chemotherapy. For stage III patients, the 5-year survival rate was 81% for patients who received adjuvant chemotherapy, compared to 56% for those who did not receive chemotherapy (hazard ratio (HR): 0.29; 95% confidence interval (CI): 0.15-0.56). The benefit of chemotherapy was found to persist after adjustment for other prognostic variables (HR: 0.47; 95% CI: 0.23-0.94).Conclusions: Patients with colon cancer in stage III who received adjuvant chemotherapy had a better overall survival.

Duodenopancreatectomia e hemicolectomia no tratamento do câncer de cólon avançado / Pancreaticoduodenectomy and hemicolectomy in the treatment of advanced colon cancer

O tratamento das lesões neoplásicas localmente avançadas de cólon permanece um desafio pelo envolvimento e invasão de órgãos como o pâncreas e o duodeno. Apresentamos um caso de câncer de cólon avançado de um paciente submetido a colectomia direita associada a duodenopancreatectomia. No seguimento de cinco anos, o paciente permanecia livre de doença. Apesar da elevada morbidade, a ressecção multivisceral associada a quimioterapia adjuvante apresenta boa sobrevida e até mesmo cura em longo prazo (AU)

The treatment of locally advanced neoplastic lesions of right colon remains a challenge due to the involvement and invasion of organs such as pancreas and duodenum. We report a case of advanced colon cancer of a patient that underwent right hemicolectomy in association with pancreaticoduodenectomy. The 5-year follow-up showed that the patient remained free of disease. Despite the high morbidity rate, multi-visceral resection associated with adjuvant chemotherapy seems to provide an increase in survival or even long-term cure (AU)

Chemotherapy-related Cognitive Impairment and Quality of Life in People with Colon Cancer: The Mediating Effect of Psychological Distress

PURPOSE: The purpose of this study was to test the mediating effect of psychological distress in the relationship between chemotherapy related cognitive impairment (CRCI) and quality of life (QOL) in people with cancer. METHODS: A purposive sample of 130 patients undergoing chemotherapy was recruited for the cross-sectional survey design. Data were collected from November 2014 to June 2015. The instruments were K-MMSE (Korean Mini-Mental State Examination), Everyday Cognition (ECog), Hospital Anxiety Depression Scale (HADS), and Functional Assessment of Cancer Therapy-General (FACT-G). Data were analyzed using descriptive statistics, correlation, and multiple regression using Baron and Kenny steps for mediation. RESULTS: The mean score for objective cognitive function was 27.95 and 69.32 for perceived cognitive decline. Overall quality of life was 91.74. The mean score was 17.52 for psychological distress. The prevalence was 56.2% for anxiety and 63.1% for depression, and 20.0% for CRCI. There were significant correlations among the variables, objective cognitive function and self-reported cognitive decline, psychological distress, and quality of life. Psychological distress was directly affected by CRCI. (R2=29%). QOL was directly affected by CRCI. Psychological distress and CRCI effected QOL (R2=43%). Psychological distress had a partial mediating effect (beta= -.56, p <.001) in the relationship between self-reported cognitive decline and quality of life (Sobel test: Z= -5.08, p <.001). CONCLUSION: Based on the findings of this study, nursing intervention programs focusing on managing cognitive decline, and decreasing psychological distress are highly recommended to improve quality of life in cancer patients.

Hemodynamic responses during and after multiple sets of stretching exercises performed with and without the Valsalva maneuver

OBJECTIVE: This study investigated the acute hemodynamic responses to multiple sets of passive stretching exercises performed with and without the Valsalva maneuver. METHODS: Fifteen healthy men aged 21 to 29 years with poor flexibility performed stretching protocols comprising 10 sets of maximal passive unilateral hip flexion, sustained for 30 seconds with equal intervals between sets. Protocols without and with the Valsalva maneuver were applied in a random counterbalanced order, separated by 48-hour intervals. Hemodynamic responses were measured by photoplethysmography pre-exercise, during the stretching sets, and post-exercise. RESULTS: The effects of stretching sets on systolic and diastolic blood pressure were cumulative until the fourth set in protocols performed with and without the Valsalva maneuver. The heart rate and rate pressure product increased in both protocols, but no additive effect was observed due to the number of sets. Hemodynamic responses were always higher when stretching was performed with the Valsalva maneuver, causing an additional elevation in the rate pressure product. CONCLUSIONS: Multiple sets of unilateral hip flexion stretching significantly increased blood pressure, heart rate, and rate pressure product values. A cumulative effect of the number of sets occurred only for systolic and diastolic blood pressure, at least in the initial sets of the stretching protocols. The performance of the Valsalva maneuver intensified all hemodynamic responses, which resulted in significant increases in cardiac work during stretching exercises. .

Redução das desigualdades no uso de consultas médicas no Brasil: análise das regiões Nordeste e Sudeste entre 2003 e 2008 / Reduction of inequalities in medical visits in Brazil: analysis of the Northeastern and Southeastern regions between 2003 and 2008

OBJETIVO: Analisar as desigualdades socioeconômicas na utilização de consultas médicas (CM) no último ano no Brasil. MÉTODOS: Dados da Pesquisa Nacional por Amostra de Domicílios (≥ 20 anos de idade) das Regiões Nordeste (2003, n = 75.652 e 2008, n = 79.779) e Sudeste (2003, n = 76.029 e 2008, n = 79.356) foram analisados segundo CM. Compararam-se as prevalências de CM segundo as variáveis exploratórias demográficas e de saúde no primeiro (D1) e último (D10) decil de renda familiar per capita. As análises consideraram o desenho amostral complexo. RESULTADOS: A proporção de pessoas com CM aumentou no período na Região Nordeste (61,2 para 66,9%) e Sudeste (67,9 para 73,5%). A diferença absoluta de CM, segundo D1 e D10 no período, foi de 6,4 pontos percentuais (pp) no Nordeste e 4,2 pp no Sudeste. Houve importante redução das desigualdades entre os homens; naqueles sem doenças crônicas; naqueles que tinham uma percepção positiva da sua saúde e naqueles sem plano de saúde com direito a CM. A Região Sudeste ainda apresentou redução entre aqueles com apenas uma morbidade autorreferida (8 pp) e com percepção negativa da saúde (6 pp). CONCLUSÃO: Houve aumento de CM no Brasil. Observa-se ainda persistente desigualdade entre os mais pobres e os mais ricos, maior no Nordeste do que no Sudeste. Políticas para a redução da desigualdade em saúde mais eficazes e equânimes devem ser adotadas no Brasil. .

OBJECTIVE: To analyze the socioeconomic inequalities in medical visits (MV) in the past year in Brazil. METHODS: Data from adults aged ≥ 20 years old who participated in the Brazilian National Household Surveys and living in the Northeastern (2003; n = 75,652 and 2008, n = 79,779) and Southeastern (2003; n = 76,029 and 2008; n = 79,356) regions were analyzed according to MV. We compared MVs according to demographic and health variables in the first (D1) and last (D10) per capita family income deciles. All analyses considered the complex cluster design. RESULTS: The proportion of people who had MV during this period increased in the Northeastern (from 61.2 to 66.9%) and the Southeastern (from 67.9 to 73.5%) regions. The absolute difference (AD) in the use of MV, according to D1 and D10 in this period, was equal to 6.4 percentage points (pp) in the Northeastern and 4.2 pp in the Southeastern regions. Significant reduction in inequalities was observed among men without chronic diseases, in those who had a positive perception of their health, and among those without health insurance which included MV. The Southeastern region has also showed significant reduction among those with chronic disease (8 pp) and with negative health self-perception (6 pp). CONCLUSION: The increasing number of MVs was found in Brazil. However, persistent inequalities were observed between the poorest and the richest, higher in the Northeastern than in the Southeastern region. More effective and equitable policies to reduce health inequalities should be adopted in Brazil. .