Targeting the NTSR2/TrkB oncogenic pathway in chronic lymphocytic leukemia.

Current therapies that target the B-cell receptor pathway or the inhibition of anti-apoptotic proteins do not prevent the progressive forms of chronic lymphocytic leukemia (CLL), have low long-term efficacy and are subject to therapeutic resistance. Deciphering the mechanisms of leukemic cell survival and searching for new specific targets therefore remain major challenges to improve the management of this disease. It was evidenced that NTSR2 (neurotensin receptor 2), through the recruitment of TRKB (tropomyosin related kinase B), induces survival pathways in leukemic B cells. We have investigated the therapeutic potential of this protein complex as a new target. The binding domain of NTSR2 and TRKB was identified and a peptide targeting the latter was designed. The peptide binds TRKB and efficiently decreases the interaction of the two proteins. It is also effectively internalized by CLL-B cells in which it notably affects Src family kinase signaling and anti-apoptotic proteins levels. It demonstrated a cytotoxic effect both in vitro on the MEC-1 cell line and ex vivo on a cohort of 30 CLL patients. Altogether, these results underline the therapeutic potential of the NTSR2/TRKB protein complex as a target in CLL and open new perspectives for the development of targeted therapies.

Daphnanes diterpenes from the latex of Hura crepitans L. And activity against human colorectal cancer cells Caco-2.

Hura crepitans (Euphorbiaceae) is a tree from South America that produces an irritant latex used as a fish poison. A bio-guided fractionation of an ethanolic extract of the latex led to the isolation and structural identification of three known daphnane-type diterpenes (1-3) including huratoxin (1), together with two new analogs (4, 5). Compound 1 was found to exhibit significant and selective cell growth inhibition against the colorectal cancer cell line Caco-2, with morphological modifications suggesting formations mimicking the intestinal crypt architecture. The underlying mechanism of 1 was further investigated, in comparison with 12-O-tetradecanoylphorbol-13-acetate (TPA), revealing two different mechanisms.

Negative information-seeking experiences of long-term prostate cancer survivors.

PURPOSE: Many prostate cancer survivors have lasting symptoms and disease-related concerns for which they seek information. To understand survivors' information-seeking experiences, we examined the topics of their information searches, their overall perceptions of the search, and perceptions of their health information seeking self-efficacy (i.e., confidence in their ability to obtain information). We hypothesized that negative search experiences and lower health information seeking self-efficacy would be associated with certain survivor characteristics such as non-white race, low income, and less education. METHODS: This was a retrospective study using data from the Michigan Prostate Cancer Survivor Study (state-based survey of long-term prostate cancer survivor outcomes, N = 2499, response rate = 38 %). Participants recalled their last search for information and reported the topics and overall experience. We conducted multivariable regression to examine the association between survivor characteristics and the information-seeking experience. RESULTS: Nearly a third (31.7 %) of prostate cancer survivors (median age of 76 years and 9 years since diagnosis) reported having negative information-seeking experiences when looking for information. However, only 13.4 % reported having low health information-seeking self-efficacy. Lower income and less education were both significantly associated with negative information-seeking experiences. CONCLUSIONS: Our findings suggest that many long-term prostate cancer survivors have negative experiences when searching for information, and lower income and less education were survivor factors related to negative information-seeking experiences. IMPLICATIONS FOR CANCER SURVIVORS: We advocate for ongoing, information needs assessment at the point-of-care as the survivorship experience progresses to assess and potentially improve survivors' quality of life.

Symptom burden and information needs in prostate cancer survivors: a case for tailored long-term survivorship care.

OBJECTIVES: To determine the relationship between long-term prostate cancer survivors' symptom burden and information needs. PATIENTS AND METHODS: We used population-based data from the Michigan Prostate Cancer Survivor Study (2499 men). We examined unadjusted differences in long-term information needs according to symptom burden and performed multivariable logistic regression to examine symptom burden and information needs adjusting for patient characteristics. RESULTS: High symptom burden was reported across all domains (sexual 44.4%, urinary 14.4%, vitality 12.7%, bowel 8.4%, emotional 7.6%) with over half of respondents (56%) reporting they needed more information. Top information needs involved recurrence, relationships, and long-term effects. Prostate cancer survivors with high symptom burden more often searched for information regardless of domain (P < 0.05). High sexual burden was associated with greater need for information about relationships [odds ratio (OR) 2.05, 95% confidence interval (CI) 1.54-2.72] and long-term effects (OR 1.60, 95% CI 1.23-2.07). High bowel burden was associated with greater information need for long-term effects (OR 2.28, 95% CI 1.43-3.63). CONCLUSIONS: Long-term prostate cancer survivors with high symptom burden need more supportive information. Tailoring information to these needs may be an efficient approach to support the growing population of long-term prostate cancer survivors.

Partner's Perspective on Long-term Sexual Dysfunction After Prostate Cancer Treatment.

OBJECTIVE: Prostate cancer is the most common type of male cancer in the United States and the negative effect of prostate cancer treatment on sexual function has been well documented. The objective of this study was to examine the long-term impact of sexual dysfunction on spouses or partners of prostate cancer survivors. METHODS: A total of 742 spouses of prostate cancer survivors was mailed surveys by the Michigan Public Health Institute, of which 379 were returned (51%). Nine surveys were excluded owing to study ineligibility. Spouses responding to the survey completed a combination of modified items from the Sexual Adjustment Questionnaire and researcher-developed items. RESULTS: Over 75% of spouses reported a decline in sex life quality after treatment. Communication about sexual issues between survivors and their health care providers was rated as good to excellent by 54.7% of partners, whereas 35.1% reported it as fair to poor. Approximately 60% of physicians initially recommended some form of sexual treatment. However, despite the persistence of sexual dysfunction, only 7% of the prostate cancer survivors were currently receiving treatment. Only 4.1% of health care providers referred the survivor to a sex therapist. CONCLUSIONS: Physicians need to understand the importance of the open, ongoing communication with prostate cancer survivors about sexual issues because sexual dysfunction seems to continue indefinitely after completion of treatment. Research on the effectiveness of behavioral interventions in restoring sexual health is critically needed for this population, especially as first-line sexual aids and medications are often not satisfactory solutions.

An assessment of gynecological cytology screening practices among health care providers nationwide.

CONTEXT: The Michigan Public Health Institute and the Michigan Cancer Consortium's Cervical Cancer Committee conducted a national survey of health care providers, thanks to funding from the Centers for Disease Control Cooperative Agreement 5U47CI000743-02. Papanicolaou test screening practices were examined, emphasizing the relationship between clinical and laboratory practices. This survey found differing screening practices among providers of women's health care. OBJECTIVES: To collect information from family medicine practitioners, women's nurse practitioners, obstetricians and gynecologists, and certified nurse-midwives on Papanicolaou and human papillomavirus testing; to discuss how those practices align with current cytology screening and follow-up recommendations from professional organizations (US Preventive Services Task Force, American Cancer Society, American College of Obstetricians and Gynecologists, and American Society for Colposcopy, and Cervical Pathology); and ultimately, to make recommendations aimed at standardizing practice performance. DESIGN: This survey was conducted in part to examine clinicians' practices and their perceptions of laboratory performance, to evaluate items that are known to enhance quality of care, and to examine factors that may prohibit universal implementation of best standards of care. The survey used a self-administered questionnaire, distributed to 9366 clinicians, with 1601 (17.1%) completed surveys. RESULTS: This assessment shows a clear lack of consensus among practitioners in performing Papanicolaou testing. It demonstrates how differently patients are tested, based on the providers' screening practices, and demonstrates specific cervical cancer screening practice disparities between and among the 4 provider groups, both in Papanicolaou testing and in the use of human papillomavirus testing. CONCLUSION: A unified mandate for screening is needed to standardize screening practices.

Evaluating long-term patient-centered outcomes following prostate cancer treatment: findings from the Michigan Prostate Cancer Survivor study.

CONTEXT: Advances in screening and treatment of prostate cancer have dramatically increased the number of survivors in the US population. Yet the effect of screening is controversial, and in some instances may not be beneficial. Previous studies have typically only reported outcomes of treatment and symptoms within a short time frame following treatment. The persistence of such symptoms over time necessitates an improvement of survivor care so that the medical and support needs of these patients are met. OBJECTIVE: This study aims to perform a patient-centered survey of prostate cancer survivors in the Michigan Cancer Registry to identify treatment side effect rates, evaluate survivors' access to preventive care services post-prostate cancer treatment, and assess the informational needs of these survivors regarding their prostate cancer. DESIGN, SETTING, AND PATIENTS: Linking case files of the Michigan Cancer Registry with records from the National Death Index, we identified prostate cancer patients diagnosed between 1985 and 2004 and alive on 31 December 2005. Participants were selected using a stratified cross-sectional sampling strategy to ensure adequate inclusion of survivors based upon race and ethnicity, urban versus rural location, and number of years since diagnosis of prostate cancer. A total of 2,499 surveys were completed and returned. MAIN OUTCOME MEASURES: (1) Physical symptoms--assessing bowel, sexual, urinary, and vitality symptoms by treatment modality. (2) Access to care--identifying whether diagnostic tests for prostate cancer (prostate-specific antigen (PSA) and digital rectal examination) were performed. Determining whether the survivors had knowledge of the "watchful waiting" paradigm for prostate cancer surveillance. (3) Informational needs--assessing whether the informational needs of patients were addressed by providers. Evaluating the significant predictors associated with seeking information about prostate cancer from any other source. Identifying what factors influenced a person to actively seek out information and what factors guide which primary information source a survivor would use. RESULTS: Median duration between prostate cancer diagnosis and survey response was 9 years. Of the study population, 80 % was diagnosed at an early stage. Survivors had reported significant problems in the 4 weeks prior to survey. Of the survivors, 88.1 % reported having a PSA test since diagnosis of prostate cancer, with 93 % of them having it done at least once per year. Of the survivors, 82.6 % reported that a healthcare provider gave them information on prostate cancer. Of this 82.6 %, 86.4 % had this information provided by a urologist, 45.4 % by a primary care physician, and 29.2 % by an oncologist. The primary source of information for these survivors was "healthcare provider" (59.2 %). CONCLUSION: Persistent symptoms subsequent to prostate cancer treatment suggest a gap in symptom management. Future research should support long-term studies of active surveillance versus active treatment outcomes to understand the feasibility of minimizing the burden of long-term physical symptoms arising from prostate cancer treatment. Clinicians must assess post-treatment distress long after treatment has ended to identify when supportive care is needed. More informational resources should be allocated to prostate cancer survivors to ensure that they are well-educated about their prognosis. IMPLICATIONS FOR CANCER SURVIVORS: This study is needed to ensure that the post-treatment symptoms of prostate cancer survivors are properly addressed and managed by healthcare providers over the long term.

Cervical cancer screening practice and knowledge among Hispanic migrant and seasonal farmworkers of Michigan.

BACKGROUND: High incidence of cervical cancer among Hispanics and low utilization of cervical screening among farmworkers led us to examine Pap test use and knowledge among Hispanic farmworkers in Michigan. METHODS: Patients and potential patients of Northwest Michigan Health Services, Inc were surveyed in 2 communities (A and B) about their screening knowledge, attitudes, and practice. RESULTS: In all, 324 farmworkers participated, including 184 seasonal and 125 migrant farmworkers. Among the entire study population, 87.7% women reported receiving a Pap test recently, with no difference between migrant and seasonal farmworkers (88.0% and 87.4%, respectively, P = .088). More women from community B reported a recent Pap (93%) compared with those from community A (83%, P = .01). Only 35% of the participants had knowledge of any cervical cancer risk factors. DISCUSSION: Migrant farmworkers may not experience more difficulty in accessing Pap tests than seasonal farmworkers in Michigan. Knowledge about cervical cancer risk factors is low and needs to be addressed in future educational interventions.

Primary care perspectives on prostate cancer survivorship: implications for improving quality of care.

OBJECTIVES: Primary care providers often care for men with prostate cancer due to its prolonged clinical course and an increasing number of survivors. However, their attitudes and care patterns are inadequately studied. In this context, we surveyed primary care providers regarding the scope of their prostate cancer survivorship care. METHODS: The 2006 Early Detection and Screening for Prostate Cancer Knowledge, Attitudes and Practice Survey conducted by the Michigan Public Health Institute investigated the beliefs and practice patterns of primary care providers in Michigan. We evaluated responses from 902 primary care providers regarding the timing and content of their prostate cancer survivorship care and relationships with specialty care. RESULTS: Two-thirds (67.6%) of providers cared for men during and after prostate cancer treatment. Providers routinely inquired about incontinence, impotence and bowel problems (83.3%), with a few (14.2%) using surveys to measure symptoms. However, only a minority felt 'very comfortable' managing the side effects of prostate cancer treatment. Clear plans (76.1%) and details regarding management of treatment complications (65.2%) from treating specialists were suboptimal. Nearly one-half (45.1%) of providers felt it was equally appropriate for them and treating specialists to provide prostate cancer survivorship care. CONCLUSIONS: Primary care providers reported that prostate cancer survivorship care is prevalent in their practice, yet few felt very comfortable managing side effects of prostate cancer treatment. To improve quality of care, implementing prostate cancer survivorship care plans across specialties, or transferring primary responsibility to primary care providers through survivorship guidelines, should be considered.

Clinical profile, quality of care, and recurrence in Arab-American and Caucasians prostate cancer patients in Michigan.

Prostate cancer is the most common cancer among men in the United States with striking differences in incidence and mortality among ethnic groups. Michigan has one of the largest concentrations of Arab Americans (AAs) in the U.S. and little is known about this ethnic minority with respect to prostate cancer. This study investigated differences in clinical profile, quality of care, and recurrence among prostate cancer survivors comparing AAs and Caucasian Americans (CAs). Participants in this study included 2499 prostate cancer survivors from the Michigan Cancer Registry from 1985 to 2004. Participants completed surveys regarding health-seeking behavior, post-treatment symptoms, quality of care and recurrence. Ethnicity was self-reported and AAs and CAs were compared with respect to clinical profile, quality of care, and recurrence. There were 52 AAs and 1886 CAs patients with AAs being younger ([Formula: see text] age 68.3 ± SD 21.4 years, [Formula: see text] age 72.3 ± SD 14.1 years, for AAs and CAs, respectively) (P = 0.05). AAs had lower socioeconomic standard than CAs (34 vs. 10.6 %, <$20,000 yearly income/year; for AAs vs. CAs, respectively) (P < 0.0001). AAs reported poorer health than AAs (7.7 vs. 3.0 % for AAs vs. CAs, respectively) (P < 0.0001). AAs were more likely to visit specialists for prostate follow-up (44.5 vs. 19.7 % visited a specialist, for AAs vs. CAs respectively) (P < 0.0001) and received supplementary healthcare workers (13 % of AAs vs. 3.1 % CAs) (P = 0.032). In addition, AAs reported higher occurrence of urinary incontinence compared to CAs (67.4 vs. 60.4 %, for AAs vs. CAs, respectively) (P = 0.001). Ethnic background was not a predictor of recurrence [(Odds ratio (OR) = 1.1 (95 % confidence intervals CI = 0.40, 2.9)] (P = 0.873) even after adjusting for age, PSA levels within the last 2 years, metastasis and hormonal therapy. While AAs prostate cancer patients were different from CAs in age, income, seeking medical care, and health reporting, ethnic background was not a predictor of recurrence. Future studies of the impact of socioeconomic, demographic and cultural factors, and health care seeking behavior on long-term survival of prostate cancer in AAs and other ethnic minorities are warranted.

Healthcare access and mammography screening in Michigan: a multilevel cross-sectional study.

BACKGROUND: Breast cancer screening rates have increased over time in the United States. However actual screening rates appear to be lower among black women compared with white women. PURPOSE: To assess determinants of breast cancer screening among women in Michigan USA, focusing on individual and neighborhood socio-economic status and healthcare access. METHODS: Data from 1163 women ages 50-74 years who participated in the 2008 Michigan Special Cancer Behavioral Risk Factor Survey were analyzed. County-level SES and healthcare access were obtained from the Area Resource File. Multilevel logistic regression models were fit using SAS Proc Glimmix to account for clustering of individual observations by county. Separate models were fit for each of the two outcomes of interest; mammography screening and clinical breast examination. For each outcome, two sequential models were fit; a model including individual level covariates and a model including county level covariates. RESULTS: After adjusting for misclassification bias, overall cancer screening rates were lower than reported by survey respondents; black women had lower mammography screening rates but higher clinical breast examination rates than white women. However, after adjusting for other individual level variables, race was not a significant predictor of screening. Having health insurance or a usual healthcare provider were the most important predictors of cancer screening. DISCUSSION: Access to healthcare is important to ensuring appropriate cancer screening among women in Michigan.

Primary care perspectives on prostate cancer screening.

Although the effectiveness of prostate cancer screening is controversial, screening rates have risen dramatically among primary care providers in the United States. The authors' findings suggest more collaboration among primary care and specialty organizations, especially with respect to decision aid endorsement, is needed to achieve more discriminatory and patient-centered prostate cancer screening.

Spatial cluster analysis of early stage breast cancer: a method for public health practice using cancer registry data.

OBJECTIVES: Cancer registries are increasingly mapping residences of patients at time of diagnosis, however, an accepted protocol for spatial analysis of these data is lacking. We undertook a public health practice-research partnership to develop a strategy for detecting spatial clusters of early stage breast cancer using registry data. METHODS: Spatial patterns of early stage breast cancer throughout Michigan were analyzed comparing several scales of spatial support, and different clustering algorithms. RESULTS: Analyses relying on point data identified spatial clusters not detected using data aggregated into census block groups, census tracts, or legislative districts. Further, using point data, Cuzick-Edwards' nearest neighbor test identified clusters not detected by the SaTScan spatial scan statistic. Regression and simulation analyses lent credibility to these findings. CONCLUSIONS: In these cluster analyses of early stage breast cancer in Michigan, spatial analyses of point data are more sensitive than analyses relying on data aggregated into polygons, and the Cuzick-Edwards' test is more sensitive than the SaTScan spatial scan statistic, with acceptable Type I error. Cuzick-Edwards' test also enables presentation of results in a manner easily communicated to public health practitioners. The approach outlined here should help cancer registries conduct and communicate results of geographic analyses.