جستجوی مقالات مرتبط با کلیدواژه "capecitabine" در نشریات گروه "پزشکی"

This study explores the combined effects of concurrent training and capecitabine consumption on breast cancer prevention and therapy, focusing on the modulation of BRCA1 gene expression.

In the main study, 12 mice were divided into groups, including Exercise-Tumor-Exercise (ETE), Exercise-Tumor-Exercise+Drug (ETE + D), and various others. Resistance and endurance training were conducted five days a week for 12 weeks before and eight weeks after tumor induction, accompanied by capecitabine administration. BRCA1 gene expression was assessed post-intervention using SPSS 20.

MC4-L2 injection induced tumors. Both pre and post-cancer induction, exercise significantly increased BRCA1 gene expression (p = 0.001, p = 0.001). Exercise combined with post-cancer capecitabine led to increased BRCA1 expression (p = 0.001). Capecitabine alone post-cancer also elevated BRCA1 expression (p = 0.001). Exercise, exercise with capecitabine, and capecitabine alone post-cancer showed significantly higher BRCA1 expression than exercise pre-cancer (p = 0.001). Exercise-tumor-exercise and Exercise-Tumor-Exercise+Drug groups exhibited increased BRCA1 expression compared to exercise-tumor-drug (p = 0.001).

The ETE+D protocol, involving exercise and capecitabine post-cancer, increased BRCA1 expression, suggesting potential roles in tumor prevention and therapy.

Invasive breast cancer is the most commonly diagnosed cancer at present. Due to systemic nature of disease, chemotherapy plays an important role in treatment of invasive breast cancer. Relapse (loco-regional or metastatic) is not uncommon in this disease. Both eribulin and capecitabine are effective as single agent in relapsed disease. But in combination, efficacy of these two chemotherapeutic medicines are not properly known. In this single-Institutional retrospective study, Eribulin and capecitabine have been assessed as combination chemotherapy in patients with relapsed breast cancer.

Patients with relapsed breast cancer, having ER and/or PR positive, Her-2/neu negative or triple negative status and received eribulin alongwith capecitabine, were included in our study. Primary objective of this study was to assess response, progression-free survival (PFS) and overall survival (OS). Secondary objective was toxicity assessment.

48 patients were included in our study. Median age of patients was 56 years. Thirty six (75%) patients had ER and/or PR positive status and twelve (25%) patients had ER/PR negative status. Five (10.4%) patients achieved complete response (CR). Thirty two (66.7%) patients achieved partial response (PR). Disease was stable (SD) in nine (18.8%) patients. Two (4.2%) patients suffered from progressive disease (PD). Median Progression-free survival (PFS) was 10.15 months. Mean of PFS of patients was 10.72 (95% CI- 9.72-11.72) months. Median overall survival (OS) was 18.15 months. Mean of overall survival of patients was 19.56 (95% CI- 17.9-21.22) months. Nineteen (39.6%) and three (6.2%) patients experienced grade 2 and grade 3 anemia respectively. Eighteen (37.5%) and two (4.2%) patients suffered from grade 2 and grade 3 neutropenia respectively. One patients experienced grade 2 thrombocytopenia. Nineteen (39.6%) patients experienced grade 2 diarrhoea. One patients suffered from grade 3 diarrhoea. Palmo-plantor erythrodysesthesia had been experienced by eight (16.7%) patients. Six (12.5%) patients suffered from grade 2 neuropathy. Two (4.2%) patients experienced grade 3 neuropathy. Fatigue had been experienced by 19 (39.6%) patients.

Eribulin alongwith capectabine can be used in patients with relapsed invasive breast cancer, in whom anthracycline and taxane have previously been used; with response rate and survival better than either single agent chemotherapy. This regimen is important particularly for triple negative breast cancer (TNBC), where option for chemotherapy is limited.

Gastric cancer is one of the most commonly known malignancies and is the fifth cancer-related death globally. Whereas natural killer (NK) cells play a critical role in tumor elimination; therefore, adoptive NK cell therapy has become a promising approach in cancer cytotherapy. Hence, this study investigated the chemoimmune cell therapy in MKN-45 derived xenograft gastric cancer model.

Three groups of animals have received the following treatments separately: activated NK cells, capecitabine, the combination of capecitabine and activated NK cells, and one was considered as the control group. Morphometric properties of tumor samples were evaluated at the end of the study. NK cells infiltration was evaluated by immunohistochemistry (IHC) of hCD56. Mitotic count and treatment response was assessed by hematoxylin and eosin (H&E) staining. The proliferation ratio to apoptosis was determined by IHC assessment of Ki67 and caspase 3.

The results indicated that the NK cell therapy could effectively decrease the mitotic count in pathology assessment, but the tumor was not completely eradicated. In combination with metronomic chemotherapy (MC) of capecitabine, NK cell therapy demonstrated a significant difference in tumor morphometric properties compared to the control group. The proliferation ratio to apoptosis was also in line with pathology data.

Although NK cell therapy could effectively decrease the mitotic count in vivo, the obtained findings indicated lesser potency than MC despite ex vivo activation. In order to enhance NK cell therapy effectiveness, suppressive features of the tumor microenvironment and inhibitory immune checkpoints blockade should be considered.

Hand-foot syndrome (HFS) is a prevalent skin reaction to cytotoxic systemic therapy, mainly Capecitabine.
The present study aimed to determine etiologies of HFS in addition to its prevention in colorectal cancer patients with Capecitabine-containing chemotherapy regimen.
In this randomized double-blinded study, we recruited 66 eligible patients. The first 33 patients received 25 mg captopril twice daily, while the other 33 were given two placebo tablets.
All the patients were assessable for safety and efficacy. Captopril demonstrated a favorable safety profile. The participants in the two groups did not have any significant differences in terms of the median age and the level of hemoglobin (P = 0.45, P = 0.06, respectively). However, the CEA tumor marker was significantly higher in those with HFS (P < 0.05). The incidence of HFS in men and women were 8 (18.6%) and 3 (13%) cases, respectively, and the patients’ sex did not affect the incidence of this syndrome (P = 0.73).
Furthermore, according to the stage of colorectal cancer, the difference between the two groups was significant (P < 0.05). Meanwhile, there were no significant differences concerning the grade of colorectal cancer (P = 0.2).
The results herein revealed that administration of captopril in colorectal cancer patients with Capecitabine-containing chemotherapy regimen reduced the symptoms and incidence of HFS.
On the other hand, CEA tumor marker and the stage of colorectal cancer were in correlation with incidence of HFS.

Patient-derived xenograft (PDX) model becomes a more and more important tool for tumor research. This study aimed to establish a colorectal cancer PDX model and verify its applicability.

Fresh human colorectal cancer tissue was surgically removed and subcutaneously inoculated into immunodeficient mice to establish the PDX model. Hematoxylin and eosin (HE) staining and immunohistochemical staining were used to evaluate the model. The successful PDX model was selected to study the efficacy of capecitabine in treating colorectal cancer. 

HE staining showed that the PDX mice model of colorectal cancer could preserve the histological characteristics of the primary tumor. Immunohistochemistry staining showed α-fetoprotein (AFP), carcinoembryonic antigen (CEA), and E-cadherin were strongly positively expressed in primary human and PDX tumor tissues, with a high degree of similarity. Capecitabine significantly inhibited PDX tumor growth and reduced the expression of AFP and CEA proteins in the tumor tissues (all Ps<0.05). 

We successfully established a colorectal cancer PDX model, and the PDX model could retain the histological and biological characteristics of the primary tumor. Using this PDX model, we revealed that capecitabine at a dose of 300–400 mg/kg can effectively treat colorectal cancer, and no significant difference in toxicity was found among different dose groups. The current work provides a feasible framework for establishing and validating the PDX tumor model to better facilitate the evaluation of drug efficacy and safety.

Adherence to capecitabine, an effective oral chemotherapy agent, is essential in achieving treatment response in cancer. In this study, we aimed to investigate factors associated with non-adherence to capecitabine in a sample of patients with gastrointestinal cancer. We enrolled 98 patients with colon, rectal or gastric cancers who were undergoing treatment with capecitabine as part of their single or multi-agent chemotherapy regimen. The patients were followed during cohort time up to four consecutive cycles of their chemotherapy. For adherence measurement, the participants were asked to bring back the leftover medicines at the time of follow-up visits and were considered adherent if they had taken ≥95% of their prescribed dose. The mean adherence rate was 97.7%, and the patients were adherent to capecitabine in 93.1% of their cycles. The patients who underwent neoadjuvant chemotherapy were significantly less adherent to capecitabine (60%) as compared with adjuvant (95.2%) and palliative chemotherapy (94.6%) [P=0.004]. Multivariable logistic regression revealed that neoadjuvant chemotherapy and the presence of nausea and mucositis were inversely associated with adherence rate. We did not find any association between adherence and any of our laboratory findings. Our findings suggest a high adherence rate to capecitabine among patients with gastrointestinal cancers. Neoadjuvant chemotherapy and the presence of nausea and mucositis may play a significant role in non-adherence to capecitabine.

Mouse breast cancer cell line 4T1 can accurately mimic the response to immune receptors and targeting therapeutic agents. Combined therapy has emerged as an important strategy with reduced side effects and maximum therapeutic effect. Mocetinostat (MGCD0103) is one of the members of Class I Histone Deacetylase Inhibitors (HDACi) and its mechanism of action has not been defined, yet. Capecitabine (Xeloda) is an antimetabolite and currently is widely utilized to treat a wide range of solid tumors. The aim of this study was to investigate the effects of the capecitabine, mocetinostat and their combined application on the 4T1 cell line.   The effects of combined administration of mocetinostat and capecitabine on 4T1 cells were investigated by cell viability and migration assays, apoptosis analysis, and Western blotting technique. The concentrations of drugs that give a half-maximal response (IC50) were detected for capecitabine (1700 µM), mocetinostat (3,125 µM), and 50 µM Capecitabine+1,5 µM Mocetinostat for 48 hr. In capecitabine+mocetinostat combine group, we observed that cell migration decreased, DNA fragmentation increased compared to the control group. capecitabine + mocetinostat group induced apoptosis by decreasing Bcl-2, PI3K, Akt, c-myc protein levels, while increasing Bax, Caspase-3, PTEN, cleaved-PARP, Caspase-7, Caspase-9, p53, cleaved-Cas-9 protein levels in 4T1 cells.  Capecitabine and mocetinostat played a toxic role through inducing apoptosis on 4T1 cancer cells in a time- and concentration-dependent manner. These results showed that combined therapy with low concentrations were detected to be more effective than that with high-concentration alone drug treatment.

Neuroendocrine tumors of the gastrointestinal tract and pancreas include a range of rare and diverse neoplasms with unique tumor biology, natural history, and clinical management. Neuroendocrine tumors of the ampulla of Vater are extremely uncommon cancers that account for only about 0.3%-1% of all gastrointestinal neuroendocrine tumors. Approximately 139 cases have been reported to date. In this paper, we describe two patients with low to intermediate grades of ampullary neuroendocrine tumors that underwent multiple courses of chemotherapy with Capecitabine (Xeloda®) and Temozolomide (Temodal®). Our two patients had a dramatic response to this regimen. According to our study, it seems that ampullary neuroendocrine tumors have behavior like pancreatic neuroendocrine tumors which requires further studies in more patients.

Dihydropyrimidine dehydrogenase (DPD) is the principal enzyme in the catabolismof fluoropyrimidine drugs including capecitabine. A recent report has suggested that oxaliplatinchemotherapy is associated with elevated DPD levels and chemoresistance pattern. As a newlydeveloped chemotherapeutic agent, 17-allyloamino-17-demethoxy-geldanamycin (17-AAG)can be effective in combination therapy with oxaliplatin and capecitabine in colorectal cancer(CRC). DPD expression level can be a predictive factor in oxaliplatin and capecitabine-basedchemotherapy. We evaluated DPD in mRNA and protein levels with new treatments: 17-AAG incombination with oxaliplatin and capecitabine in HT-29 and HCT-116 cell lines. Drug sensitivity was determined by the water-soluble tetrazolium-1 assay in aprevious survey. Then, we evaluated the expression levels of DPD and its relationship with thechemotherapy response in capecitabine, oxaliplatin, and 17-AAG treated cases in single andcombination cases in two panels of CRC cell lines. DPD gene and protein expression levels weredetermined by real-time polymerase chain reaction and western blotting assay, respectively. DPD gene expression levels insignificantly increased in single-treated cases versusuntreated controls in both cell lines versus controls. Then, the capecitabine and oxaliplatinwere added in double combinations, where DPD gene and protein expression increased incombination cases compared to pre-chemotherapy and single drug treatments. The elevated levels of cytotoxicity in more effective combinations could be relatedto a different mechanism apart from DPD mediating effects or high DPD level in the remainingresistance cells (drug-insensitive cells), which should be investigated in subsequent studies.

Combined treatment with radiotherapy and chemotherapy is the standard approach in non-metastatic anal carcinoma. Intensity-modulated radiotherapy and volumetric modulated arc therapy are currently the most accepted radiation techniques. We intend to report the clinical outcomes of patients that have been treated with volumetric modulated arc therapy concomitant with mitomycin C and capecitabine. This was a retrospective analysis of 11 patients diagnosed with anal carcinoma who received volumetric modulated arc therapy and a simultaneous integrated boost with concurrent chemotherapy. The chemotherapy protocol consisted of intravenous infusions of mitomycin C (12 mg/m2) on days 1 and 29, and oral capecitabine (825 mg/m2) twice daily with radiotherapy treatment. Most patients had stage IIIB (45.4%) disease. The majority of patients (63.7%) received a dose of 59.4Gy per 33 fractions to the primary tumor and enlarged lymph nodes (median dose: 59.4 Gy; range: 54 Gy-61 Gy). The overall treatment period ranged between 34-56 days. All patients received the planned chemotherapy protocol of two cycles with the exception of one patient who received one cycle due hematologic toxicity and intolerance. Grade 3 skin toxicity occurred in three (27.3%) patients followed by grade 3 gastrointestinal toxicities in 18.2% of patients. Grade 2 anemia (18.2%), neutropenia (27.3%), and thrombocytopenia (27.3%) were observed in eight patients. Complete response was achieved in 90.9% of patients. Patients had an overall one-year survival of 89% and overall 3-year survival of 71% (95% CI: 20.75%- 38.49%). After the median follow up period of 12 months, patients had a progression-free survival of 75% (95% CI: 21.29%-38.6%) and 2-year colostomy free survival of 68% (95% CI: 17.2%-32.1%). Volumetric modulated arc therapy is a safe and effective modality of intensity modulated radiotherapy when combined with chemotherapy (mitomycin C and capecitabine) in anal cancer patients.

The use of heat shock protein 90 inhibitors like 17-allylamino-17-demethoxy-geldanamycin (17-AAG) has been recently introduced as an attractive anticancer therapy. It has been shown that 17-AAG may potentiate the inhibitory effects of some classical anticolorectal cancer (CRC) agents. In this study, two panels of colorectal carcinoma cell lines were used to evaluate the effects of 17-AAG in combination with capecitabine and oxaliplatin as double and triple combination therapies on the proliferation of CRC cell lines. HT-29 and all HCT-116 cell lines were seeded in culture media in the presence of different doses of the mentioned drugs in single, double, and triple combinations. Water-soluble tetrazolium-1 (WST-1) assay was used to investigate cell proliferation 24 h after treatments. Then, dose-response curves were plotted using WST-1outputs, and IC50 values were determined. For double and triple combinations respectively 0.5 × IC50 and 0.25 × IC50 were used. Data was analyzed with the software CompuSyn. Drug interactions were analyzed using Chou-Talalay method to calculate the combination index (CI).The data revealed that 17-AAG shows a potent synergistic interaction (CI 1) in HT-29 and a synergistic effect (CI

Combination chemotherapy is accepted as a high efficacy treatment for gastric cancer, whereas choice of standard treatment is unclear. Multiple chemotherapeutic regimens have been used to achieve higher efficacy and lower toxicity. This study was designed to evaluate the treatment results of advanced gastric cancer with Capecitabine and Oxaliplatin regimen.
Subjects and All cases with documented gastric adenocarcinoma and advanced disease were candidates for receiving Xelox regimen (Capecitabine – 750 mg/m2/twice daily/ 1-14 days and Oxaliplatin 125 mg/m2 in 1st day).
Twenty five cases with advanced gastric cancer entered in study while 24 cases continued treatment protocol and were evaluated. Mean age was 59.5 ± 12.1 years (range: 20-75), male and female cases were 66.7% and 33.3%, respectively. All cases received at least four cycles of Xelox regimen. Overall response rate was 74.99% with 29.16% complete response. Overall survival rate was 13 ± 0.53 months and DFS (disease-free survival) was 6 ± 1.09 months. Extremities neuropathy (62.5%), headache (45.8%) and muscle cramps (29.2%) were the most common complains. Haematological changes were rare and 16.7% of cases had mild cytopenia. Treatment related death was not observed.
Xelox regimen is a safe and highly effective first line treatment for gastric cancer; however, considering it as first line therapy needs larger studies.

Capecitabine, an effective anticancer drug in colorectal cancer chemotheraphy, may create adverse side effects on healthy tissues. In the present study, we first induced colon adenocarcinoma with azoxymethane, a carcinogen agent, and then investigated the potentiality of polyamidoamine (PAMAM) dendrimer to improve capecitabine therapeutic index and decrease its adverse side effects on healthy tissues like liver and bone marrow. Other variables such as nanoparticle concentrations have also been investigated. Drug loading concentration (DLC) and encapsulation efficiency (EE) were calculated for capecitabine/dendrimer complex. Experimental results showed an increase in DLC percentage resulted from elevated capecitabine/dendrimer ratio.Capecitabine/dendrimer complex could reduce tumor size and adverse side effects in comparison with free capecitabine form.

Sorafenib, an oral multikinase inhibitor, is the only systemic agent proven to be effective in patients with hepatocellular carcinoma (HCC). There are no approved second line systemic therapies in patients who have had disease progression on or are not eligible to sorafenib.. We describe two cases of unresectable HCC that were treated with low, «metronomic» doses of capecitabine. In the first patient, capecitabine was used after sorafenib failure. In the second case, treatment with capecitabine was attempted since the patient was considered not eligible for sorafenib due to spontaneous hepatic bleeding of a large HCC lesion. Treatment was effective and well tolerated in both patients with long-lasting objective responses.. Lacking established second-line therapy, metronomic capecitabine may be a valid alternative in the treatment of HCC patients who are judged not eligible for sorafenib or those having progression disease on sorafenib..

The aim of this study was to investigate the efficacy and safety of metronomic capecitabine chemotherapy in pretreated elderly patients with advanced gastric carsonoma. Patients and Eligible patients were treated with capecitabine at a fixed dose of 1000mg daily until disease progression or toxicity. Endpoints were overall response rate, safety, progression-free survival and overall survival. Thirty eight patients were enrolled (June 2004 to October 2011) with a median age of 69 years. Two patients refused continuation due to deterioration of general condition; consequently, 36 out of 38 patients were assessed for response. No complete response was observed while 6 patients out of 36 patients (16.7%) achieved partial response, 13 (36.1%) showed stable disease and 17 (47.2%) showed progression of disease. The disease control rate (response rate + stability rate) was 52.8%. The most common hematologic adverse effects were neutropenia in 3 (8.3%), followed by mucositis in 2 (5.6%) patients. There was one reported case of neutropenic fever. The reported hand-foot syndrome cases were all lower than grade 3. There were no treatment-related deaths and treatment delays were observed in 8 patients. Symptomatic improvement was evident in 18 patients (50 %). Median follow-up period was 6.5 months. Median time to progression was 3 months (range: 0 to7 months), while the median overall survival was 7 months (range: 3 to15 months). Metronomic capecitabine may be considered an effective and tolerable treatment option in elderly patients with pretreated advanced gastric cancer after the failure of previous lines of chemotherapy.