Tattoo Removal as a Resettlement Service to Reduce Incarceration Among Mexican Migrants.

In Mexico, tattooed migrants face discrimination and are at high-risk of incarceration, thus, we assessed whether receiving laser tattoo removal affected the likelihood of incarceration. In 2015-2016, 89 adults ages ≥ 18 years with visible tattoos were recruited at a free-clinic to receive laser tattoo removal or assigned to the wait-list; all completed baseline and 6-month questionnaires. Overall, 97.8% of participants ever migrated to the USA. In multivariate analyses restricted to migrants (n = 87), those receiving laser tattoo removal [Adjusted Odds Ratio (AOR) 0.27, 95% CI 0.07-0.89] and possessing a Mexican Voting card (AOR 0.14; 95% CI 0.03-0.58) were significantly less likely than wait-list participants to be incarcerated at 6-months. Previously incarcerated participants were significantly more likely to be incarcerated at follow-up. Tattoo removal may reduce incarceration among Mexican migrants. Future studies can assess other health and social benefits of tattoo removal for migrants/deportees returning to Mexico.

Association of Adverse Childhood Experiences with Depression in Latino Migrants Residing in Tijuana, Mexico.

CONTEXT: Physical, sexual, and emotional abuse in childhood-adverse childhood experiences (ACEs)-are associated with poor mental and physical health. OBJECTIVE: To determine the prevalence of ACEs and their relationship to depression among Latino migrants in Mexico, which has not been previously examined. METHODS: A total of 110 Latinos aged 18 years and older residing in Tijuana, Mexico, completed interviewer-administered questionnaires, including the ACE scale (range = 0 to 10 items), at baseline in 2015. We studied the prevalence of ACEs (score on the ACE scale) and the presence of depressive symptoms (Patient Health Questionnaire-9). Multivariate logistic regression models were used to estimate the association between the ACE score and depressive symptoms. RESULTS: Overall, 82% of participants were men, and 82% reported being deported from the US. At least 1 ACE was reported by 64% of participants, and 33% reported 3 or more ACEs. Those who reported ever being incarcerated were significantly more likely to have 3 or more ACEs compared with no ACEs (56% vs 28%; p = 0.039). Symptoms of mild, moderate, or severe depression were identified in 14% of participants. In multivariate analyses, for each additional ACE item reported, participants were significantly more likely to meet criteria for depressive symptoms (adjusted odds ratio = 1.42; 95% confidence interval = 1.13-1.78; p = 0.002). CONCLUSION: Among Latino migrants residing in the US-Mexico border region, ACEs were pervasive and associated with depression symptoms. Programs and policies targeting migrants in this region should consider addressing both ACEs and depression.

Depressive symptoms among patients at a clinic in the Red Light District of Tijuana, Mexico.

Little is known about depression among structurally vulnerable groups living in Tijuana (e.g., migrants, deportees, substance users, sex workers, homeless) who may be at high risk for poor mental health. This study investigates the prevalence and correlates of depressive symptoms among vulnerable patients receiving services at a free clinic in Tijuana, Mexico. A convenience sample of 584 adult Mexican patients completed an interviewer-administered questionnaire in English or Spanish that included the 8-item NIH PROMIS depression short form and measures of individual, social, and structural factors affecting health. The prevalence of clinically significant depressive symptoms in our sample was 55%. In the multivariate analysis, female gender, poor/fair self-rated health, recent illicit drug use (past six months), feeling rejected (past six months), history of forced sex, and history of violence were independently associated with increased odds of experiencing depressive symptoms. When stratified by gender, we found important differences in significant factors, including recent illicit drug use in men and deportation in women. Among study participants, prevalence of depressive symptoms exceeds prevalence rates reported elsewhere in the U.S.-Mexico border region. These findings suggest that public health efforts to support mental health services in the border region are needed.

EGFR-activating mutations correlate with a Fanconi anemia-like cellular phenotype that includes PARP inhibitor sensitivity.

In patients with lung cancer whose tumors harbor activating mutations in the EGF receptor (EGFR), increased responses to platinum-based chemotherapies are seen compared with wild-type cancers. However, the mechanisms underlying this association have remained elusive. Here, we describe a cellular phenotype of cross-linker sensitivity in a subset of EGFR-mutant lung cancer cell lines that is reminiscent of the defects seen in cells impaired in the Fanconi anemia pathway, including a pronounced G2-M cell-cycle arrest and chromosomal radial formation. We identified a defect downstream of FANCD2 at the level of recruitment of FAN1 nuclease and DNA interstrand cross-link (ICL) unhooking. The effect of EGFR mutation was epistatic with FANCD2. Consistent with the known role of FANCD2 in promoting RAD51 foci formation and homologous recombination repair (HRR), EGFR-mutant cells also exhibited an impaired RAD51 foci response to ICLs, but not to DNA double-strand breaks. EGFR kinase inhibition affected RAD51 foci formation neither in EGFR-mutant nor wild-type cells. In contrast, EGFR depletion or overexpression of mutant EGFR in wild-type cells suppressed RAD51 foci, suggesting an EGFR kinase-independent regulation of DNA repair. Interestingly, EGFR-mutant cells treated with the PARP inhibitor olaparib also displayed decreased FAN1 foci induction, coupled with a putative block in a late HRR step. As a result, EGFR-mutant lung cancer cells exhibited olaparib sensitivity in vitro and in vivo. Our findings provide insight into the mechanisms of cisplatin and PARP inhibitor sensitivity of EGFR-mutant cells, yielding potential therapeutic opportunities for further treatment individualization in this genetically defined subset of lung cancer.

Detection of impaired homologous recombination repair in NSCLC cells and tissues.

INTRODUCTION: Homologous recombination repair (HRR) is a critical pathway for the repair of DNA damage caused by cisplatin or poly-ADP ribose polymerase (PARP) inhibitors. HRR may be impaired by multiple mechanisms in cancer, which complicates assessing the functional HRR status in cells. Here, we monitored the ability of non-small-cell lung cancer (NSCLC) cells to form subnuclear foci of DNA repair proteins as a surrogate of HRR proficiency. METHODS: We assessed clonogenic survival of 16 NSCLC cell lines in response to cisplatin, mitomycin C (MMC), and the PARP inhibitor olaparib. Thirteen tumor explants from patients with NSCLC were subjected to cisplatin ex vivo. Cells were assayed for foci of repair-associated proteins such as BRCA1, FANCD2, RAD51, and γ-H2AX. RESULTS: Four cell lines (25%) showed an impaired RAD51 foci-forming ability in response to cisplatin. Impaired foci formation correlated with cellular sensitivity to cisplatin, MMC and olaparib. Foci responses complemented or superseded genomic information suggesting alterations in the ATM/ATR and FA/BRCA pathways. Because baseline foci in untreated cells did not predict drug sensitivity, we adapted an ex vivo biomarker assay to monitor damage-induced RAD51 foci in NSCLC explants from patients. Ex vivo cisplatin treatment of explants identified two tumors (15%) exhibiting compromised RAD51 foci induction. CONCLUSIONS: A fraction of NSCLC harbors HRR defects that may sensitize the affected tumors to DNA-damaging agents including PARP inhibitors. We propose that foci-based functional biomarker assays represent a powerful tool for prospective determination of treatment sensitivity, but will require ex vivo techniques for induction of DNA damage to unmask the underlying HRR defect.

FANCD2 but not FANCA promotes cellular resistance to type II topoisomerase poisons.

Genetic or epigenetic inactivation of the pathway formed by the Fanconi Anemia (FA) and BRCA proteins occurs in several cancer types, including lung and breast cancer, rendering the affected tumors potentially hypersensitive to DNA crosslinking agents. However, the cytotoxicity of other commonly used cancer therapeutics in cells with FA/BRCA pathway defects remains to be defined. Building on earlier data that implicated BRCA1 and BRCA2 in the repair of DNA damage caused by the topoisomerase II poison etoposide, we studied the role of FANCD2 in mediating resistance to several topoisomerase II poisons. We establish that the loss of FANCD2 increases cell death in response to etoposide. FANCD2 promotes homologous recombination repair (HRR) and prevents DNA double-strand break formation and chromosomal aberrations in etoposide-treated cells. Strikingly, this function of FANCD2 is independent of FANCD2 foci formation and of FANCA, which is a member of the FA core complex upstream of FANCD2 mono-ubiquitination. Thus, FANCD2 appears to promote HRR in a mono-ubiquitination-independent manner in conjunction with BRCA1/2. These data add to an emerging body of evidence indicating that the FA pathway is not linear and that several protein subcomplexes with different functions exist. Our findings are potentially relevant for predicting the sensitivity of lung and breast cancers to etoposide and doxorubicin, respectively.