Research progress of acetyl-CoA carboxylase in cancer metabolism / 国际肿瘤学杂志

Abnormal fatty acid metabolism is one of the unique metabolic ways in which malignant cells maintain their growth needs and plays a crucial role in tumor progression.Acetyl-CoA carboxylase (ACC) is the rate-limiting enzyme in fatty acid synthesis and oxidative metabolism.More and more researches confirm that ACC is highly expressed in many tumors,and is closely related to tumor progression and prognosis of patients,which makes ACC as a potential marker for clinical diagnosis and prognosis.Tumor cell fatty acid synthesis can be blocked and fatty acid β oxidation can be stimulated by inhibiting the activity of ACC,resulting in serious lipid consumption of tumor,and then inhibit tumor growth and proliferation.Investigating the effect and molecular mechanisms of ACC in the genesis and development of tumors can provide a new insight into cancer targeted molecular therapy.

Presurgical targeted molecular therapy in renal cell carcinoma with inferior vena cava tumor thrombus / 中华泌尿外科杂志

Objective To investigate the therapeutic effects of presurgical TMT on the heights and levels of inferior vena cava(IVC)thrombi,and to assess its impact on surgical strategy.Methods We retrospectively reviewed data of 18 patients with renal cell carcinoma(RCC)involving IVC tumor thrombi who were treated at our hospital with presurgical TMT followed by an IVC thrombectomy.Data from 18 patients(16 men and 2 women)were included in the analysis.The median age was 53.5 years(range:33-75 years),and the mean BMI was 24.7kg/m2(rrange:18.1 -30.4 kg/m2).4 cases of tumors located in the left kidney,14 cases were right.The changes in heights and levels of the IVC thrombi were compared using computed tomography or magnetic resonance imaging.The IVC tumor thrombus level was evaluated according to the Mayo classification.Results The tumor thrombus levels before TMT were stage Ⅰ in 1 patient,Ⅱ in 1 2 patients,Ⅲ in 4 patients,and Ⅳ in 1 patient.The presurgical TMT was sorafenib in 6 patients(33.3%),sunitinib in 9(50.0%),and axitinib in 3(16.7%).After a median of 2 treatment cycles(range:1-6 cycles),three patients experienced grade 3 adverse events.One patient stopped treatment after 6 weeks owing to intolerable skin reactions and difficulty walking.The tumor thrombus height decreased measurably in 11 patients(61.1%).The thrombus height remained stable in 5 patients(27.8%)and was enlarged in 2(11.1%).The median reduction of tumor thrombus height was -0.53 cm (range:-4.23 to 1.21 cm).The median change in the maximum diameter of the thrombus was -0.30 cm (range:-1.23 to 0.29 cm).Down-staging of the thrombus level occurred in 4 patients(22.2%);the surgical strategy was modified in 3 patients(level≥Ⅲ)to avoid cardiopulmonary bypass and complicated liver mobilization under robot-assisted laparoscopy.Conclusions Our data suggest a limited influence of presurgical TMT,with a positive benefit in RCC patients with level Ⅲ and Ⅳ thrombus.Thrombus-level regression may potentially alter the surgical strategy,especially robotic surgery.Additionally,preoperative targeted therapy did not significantly increase perioperative mortality and risk of serious complications.

Uveoretinal Adverse Effects Presented during Systemic Anticancer Chemotherapy: a 10-Year Single Center Experience

BACKGROUND: The present study describes our 10-year experience with uveoretinal adverse events that manifest because of chemotherapy. METHODS: A retrospective chart review was performed for all patients who presented to the ophthalmologic department while undergoing systemic chemotherapy between July 2005 and June 2015. RESULTS: A total of 55 patients (mean age, 51.2 years, 38 women [69.1%]) suspected of having uveoretinal disease owing to the use of chemotherapeutic agents alone were enrolled. Breast cancer was the predominant disease (36.4%); noninfectious anterior uveitis (21.8%) was the most common condition. Bilateral involvement was observed in 16 patients (29.1%). Although cisplatin (21.8%) was the most commonly used drug, daunorubicin, cytarabine, tamoxifen, toremifene, and imatinib were also frequently used. The median duration until ophthalmologic diagnosis was 208.5 days (range, 19–5,945 days). The proportion of patients with final visual acuity (VA) < 20/40 Snellen VA (0.5 decimal VA) was 32.7%. However, no relationship was observed between final VA < 20/40 and age, sex, therapeutic agents, and metastasis. CONCLUSION: Uveoretinal complications were mostly mild to moderate and exhibited a favorable response to conservative therapy. A considerable number of patients exhibited significant irreversible loss of vision after cessation of the causative chemotherapeutic agent. Ophthalmological monitoring is required during chemotherapy.

Comparison of efficacy and safety between intensity-modulated radiotherapy combined with chemotherapy plus targeted therapy and intensity-modulated radiotherapy combined with chemotherapy for locally advanced nasopharyngeal carcinoma / 中华放射肿瘤学杂志

Objective To retrospectively compare the efficacy and toxicity between intensity?modulated radiotherapy ( IMRT ) combined with chemotherapy plus targeted therapy and IMRT combined with chemotherapy in the treatment of patients with locally advanced nasopharyngeal carcinoma ( NPC) , and to preliminarily evaluate the necessity of adding targeted drugs to standard chemoradiotherapy . Methods Forty?two patients with stage Ⅲ?Ⅳb NPC who received IMRT combined with concurrent ± adjuvant chemotherapy plus targeted molecular therapy from January 2007 to December 2012 were assigned to experiment group,while 168 patients who received IMRT combined with concurrent ±adjuvant chemotherapy within the same period were assigned to control group. The experiment group was paired with the control group at a ratio of 1vs.4.The survival rates were caculated using Kaplan?Meier method and analyzed using log?rank method,other comparison was perfomed by χ2?test. Results The follow?up rate was 100%.The sample size of experiment group and control group were 42 patients and 168 patients. There were no significant differences in the 3?year OS, LRFS, or DMFS rates between the experiment group and the control group (94?3% vs. 87?3%, P=0?647;100?0% vs. 94?6%,P=0?193;92?2% vs. 89?1%, P=0?744).There were also no significant differences in the incidence rates of grade Ⅲ?Ⅳ gastrointestinal reaction or marrow suppression between the two groups ( 7?1%( 3/42 ) vs. 3?6%( 6/168 ) , P=0?388;26?2%( 11/42 ) vs. 17?3%(29/168),P=0?272).However,the experiment group had significantly higher incidence of grade Ⅲ?Ⅳoral mucositis than the control group ( 40?5%( 17/42 ) vs . 14?9%( 25/168 ) , P=0?000 ) . Conclusions The preliminary results indicate that IMRT combined with chemotherapy plus targeted molecular therapy is not able to substantially improve the OS, LRFS, or DMFS rates in patients with locally advanced NPC. Moreover, it may aggravate radiochemotherapy?induced oral mucositis.

A Prospective Multicenter Trial of the Efficacy and Tolerability of Neoadjuvant Sunitinib for Inoperable Metastatic Renal Cell Carcinoma

This study aimed to evaluate the efficacy, safety, and tolerability of 2-cycled neoadjuvant sunitinib therapy (NST) in patients with inoperable metastatic renal cell carcinoma (mRCC). Between 2009 and 2012, 14 patients with inoperable mRCC from 5 Korean academic centers were prospectively enrolled after collecting their clinicopathological data and completing health-related questionnaires. The best overall response (BOR), safety profile, and changes in quality of life during NST were assessed using the RECIST criteria (version 1.0), CTCAE criteria (version 4.0), and the Cancer Quality of Life Questionnaire (QLQ-C30). Among the 14 patients, 9 patients (64.3%) experienced partial response or stable disease state, and 5 patients (35.7%) did not complete treatment, with 1 case of disease progression (7.1%), 3 grade 3 adverse events (21.4%), and 1 voluntary withdrawal (7.1%). Four patients (28.6%) were successfully converted to an operable state and underwent surgery after NST. The BOR for the primary renal lesions was 22.2%, with a median 1.3-cm diameter reduction (range: 0–2.8 cm) from a baseline diameter of 10.3 cm (range: 6.6–15.8 cm). The other 18 measurable metastatic lesions exhibited a BOR of 55.6%. The QLQ-C30 questionnaire results revealed significant improvements in the quality of life domain, although we observed significant increases in the scores for fatigue, nausea and vomiting, and the financial effects of NST (P < 0.05). Two-cycle NST provided limited efficacy for resectability of inoperable mRCC, despite mild improvements in the BOR of the primary lesion and quality of life (Clinical Trial Registry 1041140-1).

Exploration of tumor response evaluation criteria in the era of tar-geted therapy / 中国肿瘤临床

The era of targeted molecular therapy for cancer has arrived. The mechanisms of targeted molecular drugs are different from those of chemotherapy drugs. The tumor response evaluation criteria that we currently use are the summary of experiences from evaluating the effect of chemotherapy drugs. Despite continuous improvement and standardization of the details, tumor response evalua-tion criteria, from the earliest WHO criteria to the improved RECIST and RECIST 1.1 criteria, are all based on measurement of tumor size, as chemotherapy drugs directly kill tumor cells. The aforementioned criteria are outlined in this review. However, targeted molecu-lar drugs mainly inhibit tumor cell proliferation. The effect of targeted molecular drugs on tumors is different from that of chemothera-py drugs. Thus, tumor response evaluation criteria suitable for targeted molecular drugs have been developed in recent years. This re-view introduces Choi criteria that use CT attenuation coefficient (Hounsfield unit [HU]) to describe tumor density. The criteria have measured indicators that include tumor size and tumor density. This review also introduces the following criteria derived from the Choi criteria for Modified Choi (mChoi) criteria size and attenuation CT (SACT), and morphology, attenuation, size, and structure (MASS).

Cancer Treatment near the End-of-Life Becomes More Aggressive: Changes in Trend during 10 Years at a Single Institute / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to investigate and compare cancer treatment near the end-of-life (EOL) over a 10-year period. MATERIALS AND METHODS: Patients with advanced solid cancer at Seoul National University Hospital who received palliative chemotherapy and had died were enrolled. We categorized the consecutive patients according to two time periods: 2002 (n=57) and 2012 (n=206). Aggressiveness of cancer treatment near the EOL was evaluated. RESULTS: The median patient age was 62, and 65.4% of patients (n=172) were male. Time from the last chemotherapy to death (TCD) was found to have been significantly shortened, from 66.0 days to 34.0 days during 10 years (p < 0.001); 17% of patients received molecular targeted agents as the last chemotherapy regimen in 2012. The proportion of patients who received intensive care unit care within the last month increased from 1.8% in 2002 to 19.9% in 2012 (p < 0.001), and emergency room visits within the last month also increased from 22.8% to 74.8% (p < 0.001). Although hospice referral increased from 9.1% to 37.4% (p < 0.001), timing of referral was delayed from median 53 days to 8 days before death (p=0.004). Use of targeted agents as the last chemotherapy for over-two-regimen users was associated with shortened TCD (hazard ratio, 2.564; p=0.002). CONCLUSION: Cancer treatment near the EOL became more aggressive over 10 years.

A Perspective: Role of Targeted Therapy in Colon Cancer / 대한소화기학회지

Colorectal cancer is the third most common malignant disease in incidence according to a report in 2009 from Korea. The 5-fluorouracil (5-FU) remains to be a major chemotherapeutic agents. But, over the last 10-15 years, the treatment pattern for metastatic colorectal cancer changed significantly. Irinotecan and oxaliplatin are cytotoxic drugs, or bevacizumab and cetuximab are monoclonal antibodies against molecular targets. The introduction of novel agents targeting specific molecular features of cancer cells promises more options and marked improvements in efficacy for the treatment of metastatic colon cancer. Bevacizumab has been shown to extend survival in colorectal cancer when used in combination with irinotecan and 5-FU-based chemotherapy, and the addition of cetuximab to irinotecan and 5-FU-based chemotherapy eliminates irinotecan resistance. Better understanding of the tumor biology and the molecular pathway and mechanisms of tumorigenesis has led to the discovery of novel agents with improved outcomes.

A Perspective: Role of Targeted Therapy in Colon Cancer / 대한소화기학회지

Colorectal cancer is the third most common malignant disease in incidence according to a report in 2009 from Korea. The 5-fluorouracil (5-FU) remains to be a major chemotherapeutic agents. But, over the last 10-15 years, the treatment pattern for metastatic colorectal cancer changed significantly. Irinotecan and oxaliplatin are cytotoxic drugs, or bevacizumab and cetuximab are monoclonal antibodies against molecular targets. The introduction of novel agents targeting specific molecular features of cancer cells promises more options and marked improvements in efficacy for the treatment of metastatic colon cancer. Bevacizumab has been shown to extend survival in colorectal cancer when used in combination with irinotecan and 5-FU-based chemotherapy, and the addition of cetuximab to irinotecan and 5-FU-based chemotherapy eliminates irinotecan resistance. Better understanding of the tumor biology and the molecular pathway and mechanisms of tumorigenesis has led to the discovery of novel agents with improved outcomes.

Palliative treatment in advanced hepatocellular carcinoma: Has it made any difference.

Hepatocellular carcinoma (HCC) is a global health problem, the fifth most common cancer in the world.. HCC occurs in a histologically abnormal liver due to underlying chronic liver disease resulting as a sequele of the chronic viral infections, hepatitis B and C. Since these two viral infections are endemic in Asia and Africa, more than 80% of cases are encountered in these regions. In India, a large proportion of the population is “at risk” for developing chronic liver disease and, therefore, HCC. Due to the lack of screening programmes in the country, the majority of HCC patients are diagnosed at an advanced stage of the disease, and thus treatment remains a challenge. Palliative therapy forms the mainstay of treatment for this group of patients. The current era provides a plethora of options for the palliative management of HCC. This review concisely summarises the historical perspective and the current status of palliative treatment in advanced HCC.