Clinical Effect Of Chemotherapy Research Articles

The Role of Hypoxia in Endometrial Cancer.

Endometrial cancer represents the most frequent neoplasia from the corpus uteri and comprises the 14th leading cause of death in women worldwide. Risk factors that contribute to the disease include early menarche, late menopause, nulliparity, and menopausal hormone use, as well as hypertension and obesity comorbidities. The clinical effectiveness of chemotherapy is variable, suggesting that novel molecular targeted therapies against specific cellular processes associated with the maintenance of cancer cell survival and therapy resistance ameliorate the rates of success in endometrial cancer treatment. In the course of tumor growth, cancer cells must adapt to decreased oxygen availability in the microenvironment by upregulation of hypoxia-inducible factors, which orchestrate the activation of a transcriptional program leading to cell survival. During this adaptative process, the hypoxic cancer cells may acquire invasive and metastatic properties as well as increased cell proliferation and resistance to chemotherapy, enhanced angiogenesis, vasculogenic mimicry, and maintenance of cancer cell stemness, which contribute to more aggressive cancer phenotypes. Several studies have shown that hypoxia-inducible factor 1 alpha (HIF-1α) protein is aberrantly overexpressed in many solid tumors of the breast, prostate, ovarian, bladder, colon, brain, and pancreas. Thus, it has been considered an important therapeutic target. Here, we reviewed the current knowledge of the relevant roles of cellular hypoxia mechanisms and HIF-1α functions in diverse processes associated with endometrial cancer progression. In addition, we also summarize the role of microRNAs in the posttranscriptional regulation of protein-encoding genes involved in the hypoxia response in endometrial cancer. Finally, we pointed out the need for urgent targeted therapies to impair the cellular processes activated by hypoxia in the tumor microenvironment.

Curzerene suppresses progression of human glioblastoma through inhibition of glutathione S-transferase A4.

AimsGlioblastoma is the central nervous system tumor with the highest mortality rate, and the clinical effectiveness of chemotherapy is low. Curzerene can inhibit the progression of non‐small‐cell lung cancer, but its role in glioma has not been reported. The purpose of this study was to clarify the effect of curzerene on glioma progression and further explore its potential mechanism.MethodsThe expression of glutathione S‐transferase A4 (GSTA4) in glioblastoma and the effect of curzerene on the expression of GSTA4 and matrix metalloproteinase 9 and the activation of the mTOR pathway were detected by Western blotting and RT‐PCR, and the effects of curzerene treatment on glioma malignant character were detected by cell biological assays. The in vivo antitumor effects of curzerene were analyzed in a nude mouse xenograft model.ResultsCurzerene was found to inhibit the expression of GSTA4 mRNA and protein in U251 and U87 glioma cells, and this effect correlated with a downregulation of the proliferation of these cells in a time‐ and dose‐dependent manner. Invasion and migration were also inhibited, and curzerene treatment correlated with induction of apoptosis. Curzerene inhibited the activation of the mTOR pathway and the expression of matrix metalloproteinase 9, and it correlated with increased 4‐hydroxynonenal levels. In vivo, curzerene was found to significantly inhibit tumor growth in nude mice and to prolong the survival time of tumor‐bearing nude mice.ConclusionIn conclusion, inhibition of GSTA4 correlates with positive outcomes in glioma models, and thus, this molecule is a candidate drug for the treatment of glioma.

Clinical Effect of Chemotherapy Combined with Chaishao Liujunzi Decoction in the Treatment of Breast Cancer

Clinical Effect of Chemotherapy Combined with Chaishao Liujunzi Decoction in the Treatment of Breast Cancer

Anticancer Activity of Rosmarinus officinalis L.: Mechanisms of Action and Therapeutic Potentials.

Alternative treatments for neoplastic diseases with new drugs are necessary because the clinical effectiveness of chemotherapy is often reduced by collateral effects. Several natural substances of plant origin have been demonstrated to be successful in the prevention and treatment of numerous tumors. Rosmarinus officinalis L. is a herb that is cultivated in diverse areas of the world. There is increasing attention being directed towards the pharmaceutical capacities of rosemary, utilized for its anti-inflammatory, anti-infective or anticancer action. The antitumor effect of rosemary has been related to diverse mechanisms, such as the antioxidant effect, antiangiogenic properties, epigenetic actions, regulation of the immune response and anti-inflammatory response, modification of specific metabolic pathways, and increased expression of onco-suppressor genes. In this review, we aim to report the results of preclinical studies dealing with the anticancer effects of rosemary, the molecular mechanisms related to these actions, and the interactions between rosemary and anticancer drugs. The prospect of utilizing rosemary as an agent in the treatment of different neoplastic diseases is discussed. However, although the use of rosemary in the therapy of neoplasms constitutes a fascinating field of study, large and controlled studies must be conducted to definitively clarify the real impact of this substance in clinical practice.

Autophagy Machinery as a Promising Therapeutic Target in Endometrial Cancer.

Endometrial cancer is the fourth most frequent neoplasia for women worldwide, and over the past two decades it incidence has increased. The most common histological type of endometrial cancer is endometrioid adenocarcinoma, also known as type 1 endometrial cancer. Endometrioid endometrial cancer is associated with diverse epidemiological risk factors including estrogen use, obesity, diabetes, cigarette smoking, null parity, early menarche, and late menopause. Clinical effectiveness of chemotherapy is variable, indicating that novel molecular therapies against specific cellular processes associated to cell survival and resistance to therapy, such as autophagy, urged to ameliorate the rates of success in endometrial cancer treatment. Autophagy (also known as macroautophagy) is a specialized mechanism that maintains cell homeostasis which is activated in response to cellular stressors including nutrients deprivation, amino acids starvation, hypoxia, and metabolic stress to prolong cell survival via lysosomal degradation of cytoplasmic macromolecules and organelles. However, in human cancer cells, autophagy has a controversial function due to its dual role as self-protective or apoptotic. Conventional antitumor therapies including hormones, chemotherapy and ionizing radiation, may activate autophagy as a pro-survival tumor response contributing to treatment resistance. Intriguingly, if autophagy continues above reversibility of cell viability, autophagy can result in apoptosis of tumor cells. Here, we have reviewed the mechanisms of autophagy described in endometrial cancers, including the role of PI3K/AKT/mTOR, AMPK-mTOR, and p53 signaling pathways that trigger or inhibit the process and thus representing potential molecular targets in therapeutic clinical approaches. In addition, we discussed the recent findings indicating that autophagy can be modulated using repurposing drugs which may leads to faster experimentation and validation, as well as more easy access of the medications to patients. Finally, the promising role of dietary compounds and microRNAs in autophagy modulation is also discussed. In conclusion, although the research about autophagy is scarce but ongoing in endometrial cancer, the actual findings highlight the promising usefulness of novel molecules for directing targeted therapies.

Investigating the effect of chemotherapy combined with ketogenic diet on stage IV colon cancer.

e15182 Background: The effectiveness of carbohydrate restriction to limiting cancer growth has often been observed in in vitro and in vivo experiments; however, few cases of clinical efficacy have been reported. We examined the clinical effectiveness of chemotherapy with ketogenic diet for advanced cancer treatment. Methods: We administered chemotherapy with a modified medium-chain triglyceride (MCT) ketogenic diet at a ratio of 1.4:1 in 10 patients with stage IV recurrent colon cancer for one year and performed a conversion surgery in five of the cases. We followed-up for the next 3 years, compared the overall survival (OS) of the chemotherapy-only group of the stage IV colon cancer patients, and investigated the factors contributing to an improved OS. Results: Evaluations in the first year revealed a response rate of 21% and disease control rate of 64% for patients in the chemotherapy-only group. Patients in the ketogenic diet-chemotherapy combination group exhibited a response rate of 60%, disease control rate of 70%, and complete response rate of 50% for the five conversion surgeries. The time to conversion surgery was 4.0±0.9 months and the time to postoperative recurrence was 6.2±2.6 months. Regarding the duration of overall survival, there was no significant difference ( p value = 0.98) upon comparing the ketogenic diet group with the chemotherapy-only group (32.5 months and 37.9 months, respectively). However, overall survivals were 50 months, 23.0 months, and 32.5 months for the ketogenic diet-chemotherapy combination response group, ketogenic diet-chemotherapy combination non-response group, and chemotherapy-only group, respectively ( p value = 0.07). The ketogenic diet-chemotherapy combination response group tended to have a longer OS than the chemotherapy-only group. In addition, in the ketogenic diet-chemotherapy combination response group, introduction time was earlier than the ketogenic diet-chemotherapy combination non-response group for 5.7 months, with high serum ketone body levels and low blood sugar levels. Conclusions: Chemotherapy with ketogenic diet resulted in higher response and disease control rates than chemotherapy alone. Additionally, the conversion surgery rate was high and an improved OS could be expected. Therefore, ketogenic diet may be a supportive therapy to chemotherapy. Clinical trial information: 000029527.

Expression of tumor heterogeneity-related genes in esophageal squamous cell carcinoma and its predictive value for chemotherapy sensitivity

Objective To investigate the expression of excision repair cross-complementation group 1 (ERCC1) and ribonucleotide reductase subunit M1 (RRM1) in patients with esophageal squamous cell carcinoma, and the relationship between the expression of ERCC1 and RRM1 genes and chemotherapy sensitivity. Methods A total of 77 patients with esophageal squamous cell carcinoma admitted in hospital from Jan. 2008 to Dec. 2012 were recruited. ERCC1 and RRM1 mRNA levels in the cancerous tissue were detected by real-time fluorescent quantitative RT-PCR. The relationship between short-term effects of chemotherapy and ERCC1 and RRM1 mRNA levels was analyzed. Results Levels of mRNA in stages Ⅰa, Ⅰb, Ⅱa, and Ⅱb were (0.578±0.081), (0.560±0.084), (0.521±0.080), (0.464±0.091) for ERCC1 and( 0.511±0.089), (0.539±0.086), (0.584±0.092), (0.637±0.101 )for RRM1, respectively. As the clinical stage advanced, the ERCC1 mRNA level declined and the RRM1 mRNA level increased (t=2.679 and 2.952, P=0.034 and 0.025, respectively). Levels of mRNA in patients with complete remission, partial remission, stable disease and progressive disease were (0.487±0.097, 0.511±0.095, 0.552±0.086, 0.568±0.088)for ERCC1 and(0.504±0.091, 0.544±0.095, 0.595±0.093, 0.616±0.097)for RRM1, respectively. The clinical effect of chemotherapy was negatively correlated with mRNA expression of ERCC1 and RRM1 (r=0.567, P=0.032). Conclusions Levels of ERCC1 and RRM1 mRNA expression are correlated with the staging of esophageal squamous cell carcinoma and chemotherapy sensitivity, and can be used as a predictive parameter for chemotherapy sensitivity in patients with esophageal squamous cell carcinoma. Key words: DNA-Repair; Esophageal neoplasms; Antineo plastic combined chemotherapy Protocols; Genes, tumor suppressor

Impact of HBV DNA copies on clinical effects of chemotherapy combined with antiviral therapy in tumor patients with hepatitis B

Impact of HBV DNA copies on clinical effects of chemotherapy combined with antiviral therapy in tumor patients with hepatitis B

The effects of chemotherapy on primary small bowel cancer: A retrospective multicenter observational study in Japan

Small bowel cancer is relatively rare among gastrointestinal tract cancers, including esophageal, gastric and colorectal cancers. The majority of cases of small bowel cancer are diagnosed at an advanced stage, resulting in poor outcomes. The clinical effects of chemotherapy on small bowel cancer have been investigated in a limited number of studies from Europe and the USA. However, they have not yet been fully investigated in Asian countries, including Japan. This retrospective multicenter observational study was designed to investigate the efficacy of chemotherapy on small bowel cancer. A questionnaire survey was conducted in 28 hospitals affiliated with the Osaka University Hospital. We retrospectively reviewed the medical records of 61 patients with small bowel cancer (32 patients who were unable to undergo curative resection or had unresectable distant metastases and 29 who underwent curative resection), treated between 1996 and 2009, to evaluate the outcomes and the efficacy of chemotherapy. There was no significant difference in the overall survival between the patients undergoing curative resection with postoperative adjuvant chemotherapy and those without postoperative adjuvant chemotherapy. In patients with non-curative resection or unresectable distant metastases, the response rate to chemotherapy was 31.6% and the overall survival was significantly higher compared to that without chemotherapy (P=0.008). The study results suggested that chemotherapy is effective for Japanese patients with small bowel cancer who cannot undergo curative resection or have unresectable distant metastases.

Circulating Endothelial Cells in Non-small Cell Lung Cancer Patients Treated with Carboplatin and Paclitaxel

Circulating endothelial cells (CECs) increase in cancer patients and play an important role in tumor neovascularization. This study was designed to investigate the role of CEC as a marker for predicting the effectiveness of a carboplatin plus paclitaxel based first line chemotherapy in advanced non-small cell lung cancer (NSCLC). The CEC count in 4 ml of peripheral blood before starting chemotherapy (baseline value) was significantly higher in NSCLC patients, ranging from 32 to 4501/4 ml (n = 31, mean +/- SD = 595 +/- 832), than in healthy volunteers (n = 53, 46.2 +/- 86.3). We did not detect a significant correlation between the CEC count and estimated tumor volume. CECs were significantly decreased by chemotherapy as compared with pretreatment values (175.6 +/- 24 and 173.0 +/- 24, day +8, +22, respectively). We investigated the correlation between baseline CEC and the clinical effectiveness of chemotherapy. CEC values are significantly higher in patients with clinical benefit (partial response and stable disease, 516 +/- 458, 870.8 +/- 1215, respectively) than in progressive disease patients (211 +/- 150). Furthermore, a statistically significant decrease in CECs, on day 22, was observed only in patients with partial response. Patients who had a baseline CEC count greater than 400/4 ml showed a longer progression-free survival (>400, 271 days [range: 181-361] versus <400, 34 [range: 81-186], p = 0.019). CEC is suggested to be a promising predictive marker of the clinical efficacy of the CBDCA plus paclitaxel regimen in patients with NSCLC.

Clinical effects of chemotherapy in combination with radiotherapy for advanced lung cancer.

To study the curative effects by concomitant chemotherapy plus radiotherapy for advanced lung cancer. FromJanuary 1992 to December 1994 , radiotherapy was given in 52 patients with advanced lung cancer after 2-4 cycles of chemotherapy. The radiation does ranged from 55-70 Gy/ 5. 5-7 weeks. The complete response (CR) rate was 13. 5 % , and partial response (PR) rate was 51. 9 %. The overall effective (CR + PR) rate was 65. 4 %. The median survival period was 15. 3 months. Combination of chemotherapy plus radiotherapy is preferable in treating advanced lung cancer.

Clinical usefulness of chemosensitivity testing using the MTT assay

The results of in vitro chemosensitivity testing using the MTT assay of tumor cells from 140 patients were analyzed with reference to the clinical antitumor effects of the chemotherapy. One hundred and twenty-four (88.6%) of 140 specimens were successfully tested by the method of Mosmann (J Immunol Methods 65:55-63, 1983) with some modifications. When the results of the assay were compared with the clinical effects of chemotherapy in 22 patients with remaining measurable tumor lesions, the overall prediction rate was 86.4% (19/22). Among 31 patients with stage III-V gastric and colorectal carcinomas without remaining measurable tumor lesions, the survival rate of nine patients treated with drugs shown to be effective in the assay was significantly (P less than 0.05) better than that of 22 patients treated with drugs shown to be ineffective.

Correlation between drug sensitivity determined by the clonogenic cell assay and the clinical effect of chemotherapy in patients with primary lung cancer

Correlation between drug sensitivity determined by the clonogenic cell assay and the clinical effect of chemotherapy in patients with primary lung cancer

Correlation between drug sensitivity determined by clonogenic cell assay and clinical effect of chemotherapy in patients with primary lung cancer.

Correlation studies between the sensitivity of tumor cells determined by clonogenic cell assay and the clinical effect of chemotherapy were performed in patients with primary lung cancer. Thirty-four of 48 patients showed adequate colony formation (greater than or equal to 30 colonies) to test in vitro chemosensitivity. Colony formation of tumor specimens did not differ with regards to prognostic factors such as sex, age, stage, performance status, and prior chemotherapy. The two criteria of in vitro chemosensitivity employed were greater than 70% and 50% reduction in colony numbers. When in vitro chemosensitivity was defined as a colony reduction of greater than 50%, the true positive rate in the assay was 57%, while the true negative rate was 85%. In this case, the predictive accuracy was 79%. When in vitro chemosensitivity was defined as a colony reduction of greater than 70%, the true positive rate for the assay was 100%, while the true negative rate was 81%. In this case, the predictive accuracy was 82%. By Fisher's exact probability test, the overall in vitro/in vivo correlation was statistically significant (P = 0.042 less than 0.05) with the 50% cut-off point, but was not significant (P = 0.053 greater than 0.05) with the 70% cut-off point.

Evaluation of chemotherapeutic effects on gastric cancer in relation to the histological pattern.

A combination of MFC (Mitomycin-C, 5-FU and Cytosine arabinoside) was administered to 32 gastric cancer patients and study was made of the therapeutic efficacy in relation to the histological pattern. In evaluation based on the degree of cancer cell infiltration (INF), chemotherapy was more effective in cases with INF alpha and beta than those with INF gamma. As for the grade of follicular hyperplasia in regional lymph nodes of gastric cancer, the higher was the grade, the more effective was the chemotherapy. However, a significant relationship could not be observed between histological pattern of stromal reaction of the gastric cancer and clinical effects of chemotherapy. The grade of lymphocyte infiltration or connective tissue reaction in the stroma was not related with the therapeutic effects. No relationship was also obtained between the grade of sinus histiocytosis of lymphoid reaction in the lymph nodes and therapeutic effects.

Early responses to chemotherapy detected by pulse cytophotometry

DNA/cell distributions were recorded by automated cytofluorometry (=pulse cytophotometry) in bone-marrow aspirates of leukaemia and lymphosarcoma patients subjected to chemotherapy. In most cases, early perturbations in DNA/cell histographs were observed, characteristically reflecting the known mode of action of the drugs. These changes in general preceded the clinical observation of drug response. In a series of 23 measurements in 19 patients, a positive correlation between early cytophotometric changes and clinical effects of chemotherapy was observed in 17 patients. Five patients were negative for both cytophotometric and clinical reactions and one patient was probably false-positive. The validity of the assay for early detection of drug resistance in acute leukaemia and related diseases is discussed.