Staging Of Cancer Patients Research Articles

Prostate Cancer Stem Cells and Nanotechnology: A Focus on Wnt Signaling.

Prostate cancer is the most common cancer among men worldwide. However, current treatments for prostate cancer patients in advanced stage often fail because of relapse. Prostate cancer stem cells (PCSCs) are resistant to most standard therapies, and are considered to be a major mechanism of cancer metastasis and recurrence. In this review, we summarized current understanding of PCSCs and their self-renewal signaling pathways with a specific focus on Wnt signaling. Although multiple Wnt inhibitors have been developed to target PCSCs, their application is still limited by inefficient delivery and toxicity in vivo. Recently, nanotechnology has opened a new avenue for cancer drug delivery, which significantly increases specificity and reduces toxicity. These nanotechnology-based drug delivery methods showed great potential in targeting PCSCs. Here, we summarized current advancement of nanotechnology-based therapeutic strategies for targeting PCSCs and highlighted the challenges and perspectives in designing future therapies to eliminate PCSCs.

Comprehensive somatic genome alterations of urachal carcinoma

BackgroundUrachal cancer is a rare cancer that develops in the urachus. Because of its rarity, standard treatment therapies for urachal cancer are not established, and chemotherapeutic regimens for bladder cancer...

Palliative care pharmacists as advocates to conduct advance care planning.

73 Background: Advance care planning (ACP) is a process whereby individuals consider their end-of-life (EoL) treatment preferences and make them known to caregivers and clinicians in the event of decisional incapacity. We previously reported a focused ACP intervention led by a clinical social worker (J Palliat Med 2016). Based on this trial’s initial success, we aimed to evaluate this approach when led by a pharmacist. To date, no data exists regarding pharmacist-led ACP discussions. Methods: Advanced stage cancer patients were screened at a single, academic oncology palliative care clinic. Training of the pharmacist included observation of ACP interventions conducted by the clinical social worker, didactic lectures, and role playing. Subjects engaged in a 1-hour ACP intervention with a palliative care pharmacist within 4 weeks of consent. Details of the ACP intervention were documented in the electronic medical record and AD/POLST completion was encouraged but not required. The study outcome was the identification of an informed proxy. After the patient’s death, proxies were contacted to determine if EoL wishes were achieved. Descriptive analyzes were performed. Results: Patient demographics were 22 patients, who were mostly woman (n = 13), Caucasian (n = 17), married (n = 14), with a mean age ± SD of 60.3 ± 10.5 years and with gastrointestinal (n = 5) and genitourinary (n = 5) as the most common primary cancers. After the ACP intervention by the pharmacist, 21 of 22 patients identified an informed proxy. The most commonly identified proxy was a spouse (n = 13). Fourteen (64%) subjects completed an AD/POLST after the ACP intervention. As of October 2016, 27% (6/22) of patients have died. Four out of 6 patients died in a setting consistent with their EoL wishes. Mean time to death from ACP intervention was 133±132 days. Sixteen subjects remain in surveillance. Conclusions: Preliminary results suggest that a pharmacist can conduct ACP discussions to identify an informed HCP. To date, the majority of patients achieved a death concordant with their EoL wishes.

Aggressive care at the end of life: A study of practice based factors in patients with stage IV cancer.

80 Background: Numerous studies established that early utilization of palliative care-hospice services are beneficial to cancer patients. To reduce the incidence of aggressive care in terminal cancer patients, we conducted a quality improvement study to identify pertinent risk factors and develop interventions. Methods: Through chart review, we retrospectively identified patients with stage IV cancer that were followed by oncology clinic and were admitted to the University Hospital between 8/1/2015-10/31/15. For those patients who died during the last hospitalization or were discharged to hospice care, we obtained demographic, cancer related and practice related variables listed in Table. We used Mann Whitney U test and multivariable regression to find effects of factors related to length of stay (LOS) and cost of stay (COS). Results: Length of stay was significantly prolonged in those receiving chemotherapy within the past month (6 vs 3 p=0.035). Multivariate analyses found that patients with goals of care documented in the clinic had lower COS by 36.7% and LOS by 46.7%. On average, an ICU stay resulted in COS 2.2 times higher. No significant difference was seen in LOS based on a documented palliative care clinic visit or presence of an advanced directive. Conclusions: We identified practice based factors that need improvement including earlier goals of care conversations and less chemotherapy at the end of life. Identifying end stage patients in earlier admissions, collaborating with palliative care, and adding goals of care documentation to clinic note templates, are all interventions we are studying to improve care for end stage cancer patients. [Table: see text]

Validation of the CAchexia SCOre (CASCO). Staging Cancer Patients: The Use of miniCASCO as a Simplified Tool.

The CAchexia SCOre (CASCO) was described as a tool for the staging of cachectic cancer patients. The aim of this study is to show the metric properties of CASCO in order to classify cachectic cancer patients into three different groups, which are associated with a numerical scoring. The final aim was to clinically validate CASCO for its use in the classification of cachectic cancer patients in clinical practice. We carried out a case -control study that enrolled prospectively 186 cancer patients and 95 age-matched controls. The score includes five components: (1) body weight loss and composition, (2) inflammation/metabolic disturbances/immunosuppression, (3) physical performance, (4) anorexia, and (5) quality of life. The present study provides clinical validation for the use of the score. In order to show the metric properties of CASCO, three different groups of cachectic cancer patients were established according to the results obtained with the statistical approach used: mild cachexia (15 ≤ × ≤ 28), moderate cachexia (29 ≤ × ≤ 46), and severe cachexia (47 ≤ × ≤ 100). In addition, a simplified version of CASCO, MiniCASCO (MCASCO), was also presented and it contributes as a valid and easy-to-use tool for cachexia staging. Significant statistically correlations were found between CASCO and other validated indexes such as Eastern Cooperative Oncology Group (ECOG) and the subjective diagnosis of cachexia by specialized oncologists. A very significant estimated correlation between CASCO and MCASCO was found that suggests that MCASCO might constitute an easy and valid tool for the staging of the cachectic cancer patients. CASCO and MCASCO provide a new tool for the quantitative staging of cachectic cancer patients with a clear advantage over previous classifications.

Assessment of the integration between oncology and palliative care in advanced stage cancer patients.

Chemotherapy is indicated for patients with metastatic malignancy in order to improve quality of life and in some cases to increase survival. However, the greatest difficulty regarding the choice of treatment is to evaluate the clinical benefit and intrinsic toxicity of each procedure. The best strategy is the integration between oncology and palliative care, which is still mostly insufficient. The main objective of this study was to assess time to palliative care referral for cancer patients with advanced local or metastatic disease and to investigate the impact of covariates on this relationship. A retrospective, cross-sectional, observational pilot study was conducted on 286 patients divided into two groups, one consisting of metastatic patients and the other of non-metastatic patients at diagnosis. Karnofsky Performance Scale (KPS), setting, and survival time were evaluated. One hundred eighteen patients (41.25%) were metastatic and 168 (58.74%) had locally advanced malignant disease. The median time of metastatic patient referral to the group of palliative care (GPC) was 5.3months, with 39.8% referred earlier and 60.2% referred late (≥3months). 60.2% of metastatic patients were referred to the GPC with a KPS <70% and 56% of non-metastatic patients were referred earlier and 44% after 3months. There was improved survival only in metastatic patients referred to the GPC with a KPS ≥70% (p=0.02). Many oncology patients were referred late to the GPC. A higher KPS was a risk factor for late referral because only severe patients were referred earlier. Metastatic patients referred with a KPS ≥70% had a longer survival.

Analysis of prostaglandin-endoperoxide synthase-2 gene polymorphisms and risk of cervical cancer in an East Indian population: A case–control study

Abstract Background: The prostaglandin-endoperoxide synthase-2 (PTGS-2) gene appears to play a role in inflammation or tumor and mitogenesis. Genetic polymorphisms in PTGS-2 might contribute to differential PTGS-2 expression and subsequent interindividual variability in susceptibility to cancer. Aim: The goal of this study is to identify genetic variants of PTGS-2 gene in women of East India, which may associate with risk of cervical cancer. Materials and Methods: We enrolled 200 histopathologically confirmed patients with cervical cancer (age 18–60 years) (cases) and their corresponding sex-matched 200 normal individuals (controls). To identify genetic variants responsible for cervical cancer, we performed sequence analysis of PTGS-2 genes. Questionnaire survey was conducted to comprehend the demographic data, smoking status, and cancer stage of patients. Results: The genotype frequency of rs689466 polymorphism was significantly different between case and control groups (P &lt; 0.001). Compared with the wild-type genotype AA, the variant genotype GG was associated with 20-fold increased risk (P &lt; 0.001; odds ratio = 20.76; 95% confidence interval [CI]: 2.86–160.73) for cancer patients. The rs5275: exon1-+837T&gt;C polymorphism was not associated with cancer risk although this allele was correlated with decreased risk (P = 0.701; odds ratio = 0.71; 95% CI: 0.26–1.90). CC genotype was more frequently found in controls as compared with cases and showed an inverse association with the development of cervical cancer, thus suggesting a possible protective effect. Conclusions: PTGS-2 genotype rs689466: —1195A/G gene polymorphism demonstrated strongly associated with cervical cancer disease. However, exon1-+837T &gt; C polymorphism was not associated with cancer risk in East Indian women. Further studies evaluating the role of PTGS-2 gene polymorphisms in ethnically diverse populations and a larger cohort may help in understanding the etiopathogenesis of cervical cancer in women worldwide.

Quantitative Lymphoscintigraphy to Predict the Possibility of Lymphedema Development After Breast Cancer Surgery: Retrospective Clinical Study.

ObjectiveTo predict the probability of lymphedema development in breast cancer patients in the early post-operation stage, we investigated the ability of quantitative lymphoscintigraphic assessment.MethodsThis retrospective study included 201 patients without lymphedema after unilateral breast cancer surgery. Lymphoscintigraphy was performed between 4 and 8 weeks after surgery to evaluate the lymphatic system in the early postoperative stage. Quantitative lymphoscintigraphy was performed using four methods: ratio of radiopharmaceutical clearance rate of the affected to normal hand; ratio of radioactivity of the affected to normal hand; ratio of radiopharmaceutical uptake rate of the affected to normal axilla (RUA); and ratio of radioactivity of the affected to normal axilla (RRA). During a 1-year follow-up, patients with a circumferential interlimb difference of 2 cm at any measurement location and a 200-mL interlimb volume difference were diagnosed with lymphedema. We investigated the difference in quantitative lymphoscintigraphic assessment between the non-lymphedema and lymphedema groups.ResultsQuantitative lymphoscintigraphic assessment revealed that the RUA and RRA were significantly lower in the lymphedema group than in the non-lymphedema group. After adjusting the model for all significant variables (body mass index, N-stage, T-stage, type of surgery, and type of lymph node surgery), RRA was associated with lymphedema (odds ratio=0.14; 95% confidence interval, 0.04–0.46; p=0.001).ConclusionIn patients in the early postoperative stage after unilateral breast cancer surgery, quantitative lymphoscintigraphic assessment can be used to predict the probability of developing lymphedema.

Rational use of imaging to stage breast cancer: Evidences for a selective approach

Introduction:Staging investigations at diagnosis are customary to accurately assign a clinical stage before therapy. The practice of routine imaging in patients asymptomatic for metastasis is not recommended but widely adopted. This study was done to reexamine the basis behind guideline recommendations and to identify the factors predictive of asymptomatic metastasis.Methods:Oncology records of 200 breast cancer patients in clinical Stages I-III at diagnosis were prospectively reviewed. Baseline demographic information, tumor characteristics, and pathological data including molecular typing were collected. The prevalence of metastasis deduced and accuracy of bone scan, chest X-ray (CXR), liver ultrasound, and computed tomography (CT) chest analyzed. Patient and tumor characteristics predictive of asymptomatic metastasis tested for significance using appropriate statistical tests.Results:The prevalence of asymptomatic metastasis was 13.5%. Bone lesions (8%) were the most common metastatic site followed by lungs (7%) and liver (1%). Sensitivity, specificity, positive- and negative-predictive values of bone scans and CT chest were 100%, 97%, 74%, 100%, and 92%, 99%, 87, 3%, 99.4%, respectively. The above values for ultrasound abdomen and CXRs were 100%, 99%, 93%, 100% and 21%, 94%, 20%, 94%, respectively. Tumor size (P = 0.001), tumor Stage T1/T2 versus T3/T4 (P = 0.0002), nodal stages N0/N1 versus N2/N3 (P = 0.001), high histological Grade G I versus GII/GIII (P = 0.0001) and molecular types were strongly predictive of metastatic disease.Conclusion:The routine use of imaging to detect distant metastasis in asymptomatic patients is not recommended in newly diagnosed breast cancer. A selective approach may be adopted in individuals with tumor more than 5 cm, advanced nodal disease, higher histological grade, and aggressive molecular types.

A preliminary study on forced expiratory volume in 1 s/forced vital capacity to predict prognosis of patients with lung cancer

Aim: The purpose of the study is to verify if there is statistic difference of lung function before surgery based on differences in clinical characteristics (sex, age, degree of differentiation, size of tumor, tumor node metastasis (TNM), methods of surgeries, pleural metastasis, and lymph gland metastasis). Another purpose is to test if forced expiratory volume in 1 s/forced vital capacity obstruction (FEV1/FVC) is a risk factor of the prognosis of lung cancer. Methods: This retrospective study used t-test or analysis of variance to explore whether dramatic difference of lung function (FVC, FEV1, maximal voluntary ventilation [MVV], and FEV1/FVC) existed based on differences in clinical characteristics. The study used the Kaplan–Meier method to verify if FEV1/FVC could be a risk factor to predict the prognosis of lung cancer patients after surgeries. Results: The statistical results indicated that statistical difference of FVC existed between different age groups. In patients of different ages and sexes, there was statistically different MVV. Results of FEV1/FVC showed that FEV1/FVC varied dramatically in patients of different pleural metastasis conditions or TNM. Analysis of prognosis proved that in patients with a different differentiation degree, size of tumor, metastasis conditions of lymph gland, and TNM stage, a statistically different prognosis was found. As for groups of normal and abnormal FEV1/FVC, no apparently different prognosis was observed. Analysis of lung cancer patients of stage I indicated that the 5-year survival was dramatically different between patients of normal and abnormal FEV1/FVC. Conclusion: In lung cancer patients of stage I, FEV1/FVC was one of the risk factors of prognosis.

Equally Knocking on the Door of Medical Breakthroughs: Safety and Efficacy of a New Anti-Cancer Drug Pamica (PICNH&amp;lt;sub&amp;gt;2&amp;lt;/sub&amp;gt;Ca) for Late Stage Cancer Patients

The composition of Pamica (PICNH2Ca2) is dsRNA polyI:C, non-biotics amino compounds and CaCl2. It is the second generation noncytotoxic product of PICKCa (PIKA) adjuvant which was found effective in phase II clinical trial for PICKCa rabies vaccine and phase I trial for PICKCa hepatitis B vaccine in Singapore. With their knowledge and consent, cancer patients, regardless of their tumor types or performance status (ECOG above 5 or ECOG > 20), who were unresponsive to standard treatment, were treated free of charge with Pamica by injection or nasal spray. The primary results indicated that Pamica had no side effect except for a few cases of local pain in the site of injection and appeared to markedly improve cancer patients’ appetite, physical strength, quality of life and extended patients’ life for months and counting. These preliminary findings underlined promise of this potentially life-saving drug. In the hope of cooperating with the proper authorities, companies, and hospitals to benefit patients at the earliest opportunity, we share our findings in this paper.

ED02.05 Palliative Care in Iran

It is well known that palliative care is a necessity in cancer patients, as early on as the time of diagnosis. In adult oncology, there is evidence to suggest early specialist palliative care improves HRQOL, mood, treatment decision-making, health-care utilization, advanced care planning, patient satisfaction, and end-of-life care.1 Early admission to community-based palliative care also reduces the use of Emergency departments by cancer patients in the 90 days before death.2 Palliative care for cancer patients is rather new in Iran and has a history of less than 7 years. Here we give an overview on the status of palliative care in Iran. We also present the demographics of our patients in the first and largest palliative care ward in Iran over the last two years. Iran has a population of around 80 million people. In Iran, cancer is known as the third cause of death. Adult morbidity rate of cancer in different regions of Iran is estimated 48-112 cases per million people among the females and 51-144 cases per million people among the males.3 Also, mortality rate related to cancer was about 53500 people in 2014.4 The majority of cancer patients expire in the intensive care units (ICU), whereas bed occupancy of ICUs is in crises, being about 100% in Iran. For each ICU bed, 4 people are applicants.5 We currently have around 8 active palliative care units for cancer patients and one palliative care ward in Iran, all run by charities. In these palliative care units, we have oncologists, palliative care specialists, pain specialists, psychologists, spiritual care specialists, social workers and dieticians. A total number of 3677 patients, ages between 16 and 94 (Median 61), of whom 3277 (89%) with a similar age distribution had a cancer diagnosis were referred to our palliative care unit in Firoozgar Hospital, which is run by the Ala Charity, in Tehran in the last three years. 1770 female (54%) and 1457 male (46%) advanced cancer patients were referred. A number of 388 (12%) patients had breast cancer, 339 (10%) had hematologic malignancies, 312 (10%) had esophageal or gastric cancer, 311 (10%) had colorectal cancer, 105 (3%) had a cancer of the CNS, 101 (3%) had lymphoma, 93 (3%) had renal cancer, 87 patients (3%) had ovarian cancer, 81 (2%) had lung cancer, 54 patients (2%) had prostate cancer and 50 (2%) had pancreatic cancer. The other 40% of the cancer patients had either less frequent cancers or their exact cancer site was not recorded. In most countries, the gap between death and specific therapies is considered as an indicator of the quality of physician services and more length of time will be a better indicator for physician services, while cancer patients in health system of Iran receive specific treatment and chemotherapy even to moment of death. To consider countless benefits of home care and the patients’ desire to receive services at home, if we can provide the conditions that at least 20% of end stage cancer patients receive home based palliative care, 1000 deaths will occur at home yearly, and 1000 ICU beds will be released for use for other patients with better prognosis for survival.5 For this reason, the Ala charity has also started free of charge home care services in Isfahan and Tehran. Iran, like many other countries, needs many more palliative care units as well as an expansion of home based palliative care services to advanced and very advanced cancer patients. As palliative medicine is not financially lucrative, charities play a major role in setting up, maintaining and expanding these units. 1. Salins N, Ramanjulu R, Patra L, Deodhar J, Muckaden MA. Integration of Early Specialist Palliative Care in Cancer Care and Patient Related Outcomes: A Critical Review of Evidence. Indian J Palliat Care. (2016) 22:252-7 2. McNamara BA, Rosenwax LK, Murray K, Currow DC. Early admission to community-based palliative care reduces use of emergency departments in the ninety days before death. J Palliat Med. (2013);16:774-9 3. Mousavi SM, Gouya MM, Ramazani R, et al. Cancer incidence and mortality in Iran. Annals of Oncology. (2009);20:556-63. 4. World Health Organization. Cancer country profiles in Iran 2014. Geneva: WHO; 2014. [cited 29 August 2015]. Avilable from: http://www.who.int/cancer/country-profiles/en/ 5. Heydari H. Home-based Palliative Care: A Strategy for Keeping Intensive Care Unit Beds Vacant. Int J Community Based Nurs Midwifery. (2016);4:186-7. Palliative medicine, cancer, Iran

PUB078 Difficulties in Providing Palliative Care for Advanced Lung Cancer Patients in Rural India (West Bengal) - Experience of an NGO

As in any developing countries state of West Bengal in India has a huge burden of metastatic Lung cancer patients in advanced stage coming from rural area where awareness regarding the usefulness of palliative care in rather poor. Our goal is to give a pain free good quality of life in these advanced stage Lung cancer patients. Objective of this study is to identify the main difficulties in achieving the above goal in a rural village setting in India. Advanced Lung cancer patients in need of palliative care in various villages in of rural India were selected for this study. Their symptoms and managements in that rural surroundings were evaluated by an NGO (under the guidance of a senior palliative care specialist) working in that area. An attempt was made to identify the main obstacles in getting proper palliative care in a rural setting. Pain, fatigue, distress, effusion are the main symptoms effecting these patients. In most patients pain and other symptoms control were grossly inadequate due to lack of properly trained manpower in the rural India. However regular homecare visits by a group of social workers were of immense help in the last few months of life. NGO team was well guided by a palliative care specialist. There is a wide gap of trained manpower in this filled in rural areas of India. Dedicated groups from rural area itself need encouragement, repeated home visit, awareness built up, proper training to home care giver, so that difficult symptoms can be managed locally along with necessary social and psychological support to these patients.

495P Difficulties in providing palliative care in rural India (West Bengal) - experience of an NGO

Background As in any developing countries state of West Bengal in India has a huge burden of cancer patients in advanced stage coming from rural area where awareness regarding the usefulness of palliative care in rather poor. Our goal is to give a pain free good quality of life in these advanced stage cancer patients. Objective of this study is to identify the main difficulties in achieving the above goal in a rural village setting in India. Methods Advanced cancer patients in need of palliative care in various villages in of rural India were selected for this study. Their symptoms and managements in that rural surroundings were evaluated by an NGO (under the guidance of a senior palliative care specialist) working in that area. An attempt was made to identify the main obstacles in getting proper palliative care in a rural setting. Results Pain, fatigue are the main symptoms effecting these patients. In most patients pain and other symptoms control were grossly inadequate due to lack of properly trained manpower in the rural India. However regular homecare visits by a group of social workers were of immense help in the last few months of life. NGO team was well guided by a palliative care specialist. Conclusions There is a wide gap of trained manpower in this filled in rural areas of India. Dedicated groups from rural area itself need encouragement and proper training, so that difficult symptoms can be managed locally along with necessary social and psychological support to these patients. Legal entity responsible for the study Dr. Shyamal Kumar Sarkar Funding MAS Clinic & Hospital Disclosure All authors have declared no conflicts of interest.

Advanced-Stage Colorectal Cancer in Persons Younger Than 50 Years Not Associated With Longer Duration of Symptoms or Time to Diagnosis.

The incidence of colorectal cancer (CRC) is increasing in the United States among adults younger than the age of 50 years. Studies of young-onset CRC have focused on outcomes and treatment patterns. We examined patient presentation, provider evaluation, and time to diagnosis, which can affect stage and prognosis. In a retrospective study, we collected data from patients with a diagnosis of colorectal adenocarcinoma, confirmed by pathologists, seen at the Stanford Cancer Institute from January 1, 2008, through December 31, 2014. We compared symptoms, clinical features, time to diagnosis, and cancer stage in patients with young-onset CRC (diagnosed at an age younger than 50 years; n= 253) with patients diagnosed with CRC at an age of 50 years or older (n= 232). A higher proportion of patients with young-onset CRC were diagnosed with advanced-stage tumors (72%) compared with older patients (63%) (P= .03). Larger proportions of patients with young-onset CRC also had a family history of CRC (25% vs 17% in older patients; P= .03), confirmed or probable hereditary cancer syndromes (7% vs 1% in older patients; P < .01), and left-sided disease (distal colon cancer in 41% vs 34% in older patients; P= .01; and rectal cancer in 40% vs 35% in older patients; P= .29). Patients with young-onset CRC had a significantly longer median time to diagnosis (128 vs 79 days for older patients; P < .05), symptom duration (60 vs 30 days for older patients; P < .01), and time of evaluation (31 vs 22 days; P < .05). In multivariable analyses, time to diagnosis was 1.4-fold longer for younger than for older patients (P < .01). Among younger patients, those with stage III or IV CRC had shorter durations of symptoms and evaluations than those with stage I or II CRC. In a retrospective analysis of patients with CRC, we found that greater proportions of patients younger than 50 years were diagnosed with advanced-stage tumors than older patients; this difference could not be explained simply by delays from symptom onset to diagnosis. Although tumor biology may be an important determinant of stage at diagnosis, clinicians should be aware of CRC alarm symptoms, family history, and genetic syndromes, to speed evaluation and diagnosis of younger patients and potentially improve outcomes. It remains to be determined whether subgroups of persons at risk for young-onset CRC who benefit from early screening can be identified.

Prognostic significance of USP33 in advanced colorectal cancer patients: new insights into β-arrestin-dependent ERK signaling.

Patients with liver metastases of colorectal cancer (CRCLM) have a poorer prognosis compared to colorectal cancer (CRC) patients in local stage. Evaluating the recurrence and overall survival of advanced patients is critical in improving disease treatment and clinical outcome. Here we investigated the expression pattern of USP33, a deubiquitinating enzyme, in both primary CRC tissues and liver metastases tissues. Univariate and multivariate analyses identified that low expression of USP33 in CRCLM tissues indicated high recurrence risk and poor overall prognosis. Overexpression of USP33 can significantly inhibit cell proliferation, migration, and invasion. On the other hand, USP33 knock-down promoted cell proliferation and invasion under SDF-1 stimulation; whereas dynasore (an internalization inhibitor) pretreatment in USP33 silencing cells showed a distinct antipromoting effect, revealing the participation of CXCR4 internalization in regulating tumor progress. Further results verified that USP33 can deubiquitinate β-arrestin2, subsequently block the internalization of SDF-1-stimulated CXCR4, and disrupt β-arrestin-dependent ERK activation. The existence and functions of β-arrestin-dependent signaling have been previously determined in several Gs-coupled receptors, such as β2-adrenergic receptor and angiotensin receptor subtype 1a; however, little is known about this in Gi-coupled receptors. Our study not only established USP33 as a novel prognosis biomarker in advanced CRCLM patients, but also highlighted the significance of β-arrestin-dependent ERK signaling in cancer development.

Physical exercise in advanced cancer patients undergoing palliative treatment

ABSTRACTIntroduction: Physical exercise intervention programs show beneficial effects in early stage cancer patients during and after treatment. There is also growing evidence that physical exercise is safe and feasible for advanced cancer patients but knowledge is limited.Areas covered: This review provides an overview of randomized controlled exercise trials implemented in palliative care settings with advanced cancer patients. A comprehensive literature search was carried out in PubMed (MEDLINE), CINAHL, and the Cochrane Library. Six articles providing data of 590 patients met the predefined inclusion criteria. Mainly resistance exercise was applied and duration of interventions was between 8 and 16 weeks.Expert commentary: Beneficial effects for exercise patients were reported for both physical and psychological outcomes. However, general exercise recommendation for patients undergoing palliative treatment cannot be derived from the six analyzed studies. This is due to large heterogeneity of the appli...

Cancer Diagnostics via Ultrasensitive Multiplexed Detection of Parathyroid Hormone-Related Peptides with a Microfluidic Immunoarray.

Parathyroid hormone-related peptide (PTHrP) is recognized as the major causative agent of humoral hypercalcemia of malignancy (HHM). The paraneoplastic PTHrP has also been implicated in tumor progression and metastasis of many human cancers. Conventional PTHrP detection methods like immunoradiometric assay (IRMA) lack the sensitivity required to measure target peptide levels prior to the development of hypercalcemia. In general, sensitive, multiplexed peptide measurement by immunoassay represents challenges that we address in this paper. We describe here the first ultrasensitive multiplexed peptide assay to measure intact PTHrP 1-173 as well as circulating N-terminal and C-terminal peptide fragments. This versatile approach should apply to almost any collection of peptides that are long enough to present binding sites for two antibodies. To target PTHrP, we employed a microfluidic immunoarray featuring a chamber for online capture of the peptides from serum onto magnetic beads decorated with massive numbers of peptide-specific antibodies and enzyme labels. Magnetic bead-peptide conjugates were then washed and sent to a detection chamber housing an antibody-modified 8-electrode array fabricated by inkjet printing of gold nanoparticles. Limits of detection (LODs) of 150 aM (∼1000-fold lower than IRMA) in 5 μL of serum were achieved for simultaneous detection of PTHrP isoforms and peptide fragments in 30 min. Good correlation for patient samples was found with IRMA (n = 57); r2 = 0.99 assaying PTHrP 1-86 equiv fragments. Analysis by a receiver operating characteristic (ROC) plot gave an area under the curve of 0.96, 80–83% clinical sensitivity, and 96–100% clinical specificity. Results suggest that PTHrP1-173 isoform and its short C-terminal fragments are the predominant circulating forms of PTHrP. This new ultrasensitive, multiplexed assay for PTHrP and fragments is promising for clinical diagnosis, prognosis, and therapeutic monitoring from early to advanced stage cancer patients and to examine underlying mechanisms of PTHrP overproduction.

Aberrant expression of KPNA2 is associated with a poor prognosis and contributes to OCT4 nuclear transportation in bladder cancer.

Recent studies show that Karyopherin alpha 2 (KPNA2) is up-regulated in quite a number of cancers and associated with poor prognosis. Here, we found that expression levels of KPNA2 and OCT4 are up-regulated in bladder cancer tissues and significantly associated with primary tumor stage and bladder cancer patients' poorer prognosis. Our data also showed decreased cell proliferation and migration rates of bladder cancer cell lines when the expression of KPNA2 and OCT4 was silenced. Meanwhile, cell apoptosis rate was increased. Furthermore, Co-IP and immunofluorescence assay showed the KPNA2 interacts with OCT4 and inhibits OCT4 nuclear transportation when KPNA2 was silenced. Thus, we confirmed that up-regulated KPNA2 and OCT4 expression is a common feature of bladder cancer that is correlated with increased aggressive tumor behavior. Also, we propose that KPNA2 regulates the process of OCT4 nuclear transportation in bladder cancer.

Physical and psychological correlates of high somatic symptom severity in Chinese breast cancer patients.

We researched associations between somatic symptom severity (SSS), and physical and psychological factors in Chinese breast cancer patients. This multicenter cross-sectional study enrolled 255 Chinese breast cancer patients of different stages and treatment phases. They answered standard instruments assessing SSS (Patient Health Questionnaire [PHQ]-15), depression (PHQ-9), anxiety (General Anxiety Disorder [GAD]-7), health anxiety (Whiteley-7 [WI-7]), illness perception (Brief-Illness Perception Questionnaire [IPQ]), illness attribution (Illness Perception Questionnaire-Revised [IPQ-R]), and sense of coherence (Sense of Coherence [SOC]-9). Logistic regression was applied to identify the strongest correlates with SSS. Our sample of high (PHQ-15≥10) and low SSS differed significantly in the following physical and psychological variables: symptom duration (r=0.339, P<.001), symptom-related disability (Karnofsky Index) (r=0.182, P<.001), depression (r=0.556, P<.001), anxiety (r=0.433, P<.001), health anxiety (r=0.400, P<.001), illness perception (r=0.349, P<.001), psychological illness attributions (r=0.217, P<.01), and sense of coherence (r=-0.254, P<.001). In an adjusted stepwise multiple binary logistic regression analysis, higher health anxiety (WI-7, B=0.388, P=.002), higher depression (PHQ-9, B=0.158, P<.001), younger age (B=-0.042, P=.048), higher impairment in daily life (B=1.098, P=.010), and longer symptom duration (Wald=18.487, P=.001) showed a significant association with high SSS; the model explained 55.1% of the variance. High somatic symptom burden in breast cancer is associated with physical and psychosocial features. The results are a basis for further research to evaluate the new Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, SSD concept in cancer patients and to better operationalize psychobehavioral factors in this patient group.