State-of-the-Art Management of Colorectal Cancer: Treatment Advances and Innovation.

Colorectal cancer (CRC) remains a significant global health challenge, ranking among the leading causes of cancer-related morbidity and mortality worldwide. Recent advancements in molecular characterization have revolutionized our understanding of the heterogeneity within colorectal tumors, particularly in the context of tumor sidedness. Tumor sidedness, referring to the location of the primary tumor in either the right or left colon, has emerged as a critical factor influencing prognosis and treatment responses in metastatic CRC. Molecular underpinnings of CRC, the impact of tumor sidedness, and how this knowledge guides therapeutic decisions in the era of precision medicine have led to improved outcomes and better quality of life in patients. The emergence of circulating tumor DNA as a prognostic and predictive tool in CRC heralds promising advancements in the diagnosis and monitoring of the disease. This innovation facilitates better patient selection for exploration of additional treatment options. As the field progresses, with investigational agents demonstrating potential as future treatments for refractory metastatic CRC, new avenues for enhancing outcomes in this challenging disease are emerging.

Mental health outcomes of multiracial individuals: A systematic review between the years 2016 and 2022.

BACKGROUND: Emerging evidence suggests that multiracial individuals are at high risk for mental health problems. Systematic and ongoing synthesis of literature is necessary to understand mental health among multiracial individuals. METHODS: We conducted a systematic review of scholarly articles published during the years 2016-2022. Studies must have focused explicitly on mental health outcomes of biracial/multiracial individuals using quantitative methods. A total of 22 articles met criteria for this review. RESULTS: Studies were mainly from the United States, with one study from the United Kingdom and one from the Netherlands. Sample sizes ranged from 57 to 393,681. Findings revealed a complicated picture between multiracial identity and mental health, which may be a function of how multiracial identity is defined and empirically examined. Among studies comparing multiracial individuals with monoracial groups, multiracial individuals tended to have worse mental health, with notable exceptions depending on the multiracial subgroup, the mental health outcome, and the reference group. Among studies that only examined multiracial individuals, discrimination and ethno-racial identity emerged as complex explanatory factors that can shape mental health, though each of these constructs can be explored more deeply across social milieu. LIMITATIONS: The review focused on studies explicitly examining multiracial mental health, published during a limited time frame. CONCLUSION: Multiracial individuals tended to have worse mental health outcomes compared to their monoracial counterparts, with variations depending on the outcomes, populations/subgroups, contexts, and reference groups. Racial discrimination and ethno-racial identity may shape mental health trajectories of multiracial people, calling for more research to inform targeted interventions.

Phase II study of trifluridine/tipiracil in metastatic breast cancers with or without prior exposure to fluoropyrimidines.

BACKGROUND: Fluoropyrimidines are commonly used in the treatment of metastatic breast cancer (MBC), and trifluridine/tipiracil (FTD/TPI) has shown activity in patients with colorectal and gastric cancers despite prior exposure to fluoropyrimidines. We investigate the role of FTD/TPI in patients with MBC with or without prior fluoropyridines in a single-arm phase II study. METHODS: Patients with MBC were enroled first into a run-in dose confirmation phase, followed by two parallel cohorts including patients with (Cohort A) and without (Cohort B) prior exposure to fluoropyrimidines, where they were treated with FTD/TPI. Primary objectives for each cohort included determination of progression-free survival (PFS), and secondary objectives included determination of objective response rates (ORR), safety, and tolerability. RESULTS: Seventy-four patients (42 Cohort A, 32 Cohort B) were enroled, all of whom were evaluable for toxicity and survival, with 72 evaluable for response. Median PFS was 5.7 months (95% confidence interval 3.8-8.3) and 9.4 months (95% CI 5.5-14.0) respectively in Cohorts A and B. Responses were observed regardless of prior exposure to fluoropyrimidines, with ORR of 19.5% (95% CI 8.8-34.9) and 16.1% (95% CI 5.5-33.7) in Cohorts A and B, and 6-month clinical benefit rates of 56.1% (95% CI 39.7-71.5) and 61.3% (95% CI 42.2-78.2) respectively. The safety profile was consistent with known toxicities of FTD/TPI, including neutropenia, fatigue, nausea, and anorexia, mitigated with dose modifications. CONCLUSION: FTD/TPI showed promising antitumour activity with manageable toxicity and is a clinically valid option in patients with MBC.

Therapeutic comparison in psychological capital.

Aim: This study aimed to investigate and compare the therapeutic outcomes of psychological capital between narrative therapy, cognitive-behavioral therapy, and play therapy in the context of hikikomori. Methods: This study included 502 hikikomori. Correlation analysis was performed to investigate the relationship between the three forms of therapy and psychological capital, while one-way ANOVA and independent samples t-tests were performed to determine the differences in the outcomes of psychological capital between the three forms of therapies. Results: Results indicated that all three forms of therapy were significantly positively related to psychological capital. Moreover, while cognitive-behavioral therapy performed better in psychological capital (overall score) than the other two, cognitive-behavioral therapy performed better in the subscales "self-efficacy" and "resilience," while narrative therapy performed better in the "hope" and "optimism" subscales. Also, combining features of play therapy helped enhance the outcomes of narrative therapy and cognitive-behavioral therapy on psychological capital. Conclusion: Owing to the varied outcomes of psychological capital among different therapies, the differential use of therapies to deal with the unique needs resultant of hikikomori helps achieve optimal results.

Understanding the life experiences of elderly in social isolation from the social systems perspective: using Hong Kong as an illustrating example.

Aim: The elderly in social isolation often referred to as older people who experience social alienation with little social support from their family, peers, and community suffer from a poor quality of life and well-being. Since their life experiences are affected by a range of factors from different levels, this study seeks to investigate their current life situations and experiences from a social systems perspective. Methods: A qualitative study was conducted to enrich the understanding of their current life situations and experiences and to generate corresponding practice implications. In this study, there were 13 elderly participants in social isolation, which were users of a social service agency in Hong Kong. They took part in a semi-structured individual interview, sharing their life stories about their daily lives, social relationships, and sense of well-being. Qualitative results were analyzed based on these dimensions. Results: Results showed that the elderly participants in social isolation had a low level of social support and participation in social activities. Their life experiences and situations were affected by multiple levels of factors that were interrelated. Conclusion: The results support the application of the social systems perspective in investigating the living conditions of the elderly in social isolation. The corresponding practice implications were also discussed.

Young people's perceptions of the challenges and opportunities during the Mainland China-Hong Kong convergence.

Since the handover of the sovereignty of Hong Kong from Britain to China in 1997, convergence between Mainland China and Hong Kong has gradually emerged. During this process, young people have engaged in demonstrations to express their dissatisfaction with government policies and limited socio-economic progression. However, the underlying reasons for their dissatisfaction have not been fully investigated. This study investigates their perceived challenges and opportunities during the convergence, with the objective of identifying the factors affecting the Mainland China-Hong Kong convergence and examining young people's perceived challenges and opportunities during the convergence. Mixed research methods of focus groups and a survey were adopted. Ten focus groups with 83 participants were conducted to collect qualitative data on the factors relating to convergence. Based on the qualitative data, a questionnaire was constructed to investigate young people's perceived challenges and opportunities during the convergence, using a sample of 1253 young people. Ordinary least-squares regression was applied to analyse the relationships among identified factors. The study found that Hong Kong's youth tended to regard the Mainland China-Hong Kong convergence as an opportunity for socio-economic progression, and they identified three challenges during the convergence. It also revealed that young people's higher education, perceived housing challenges, and perceived socio-economic challenges are negatively related to the convergence, whereas their perceived challenges associated with entrepreneurship and innovation are positively related to the convergence. The development of more well-balanced and mutually beneficial policies that satisfy the needs of young people will lead to a higher acceptance of the convergence. As such, young people will be more willing to embrace the opportunities and face the challenges brought about by the convergence, resulting in a more harmonious society and socio-economic progression.

Use of theatresports to promote positive education among youth participants.

BACKGROUND: Due to the scarcity of research on the benefits of theatresports for youth, this study examined the outcomes of theatresports as a means to implement positive education in youth work settings. METHODS: To this end, qualitative research was conducted with 92 participants in a theatresports program. Thematic analysis was applied to analyze the participants' experiences of the program, using the framework of positive education. RESULTS: Results showed that the processes and practices of the theatresports program helped the participants achieved well-being in terms of various domains namely positive emotions, positive health, positive relationships, positive engagement, positive accomplishment, and positive meaning. These capabilities and qualities acquired helped them achieve well-being, and the learning acquired from the program could even be applied to daily life situations and deal with the challenges. CONCLUSIONS: This shows that the theatresports program manifests the benefits of positive education. Corresponding implications were discussed.

Clinical relevance of PD-1 positive CD8 T-cells in gastric cancer.

BACKGROUND: We evaluated the relevance of PD-1+CD8+ T-cells in gastric cancer (GC) including prognostic significance, association with chemotherapy and immunotherapy sensitivity and correlations with the tumor microenvironment (TME). METHODS: Discovery cohort: GC samples were evaluated for AE1/3, CD8, PD-1, Ki-67 and Granzyme-B expression with fluorescence-based multiplex immunohistochemistry (mIHC). Validation cohorts: we analyzed bulk RNAseq GC datasets from TCGA, the "3G" chemotherapy trial and an immunotherapy phase 2 trial. The cox proportional hazards model was used to identify factors that influenced overall survival (OS). To study the TME, we analyzed single-cell RNAseq performed on GCs. RESULTS: In the discovery cohort of 350 GCs, increased PD-1 expression of CD8 T-cells was prognostic for OS (HR 0.822, p = 0.042). PD-1 expression in CD8 T-cells highly correlated with cytolytic [Granzyme-B+] (r = 0.714, p < 0.001) and proliferative [Ki-67+] (r = 0.798, p < 0.001) activity. Analysis of bulk RNAseq datasets showed tumors with high PD-1 and CD8A expression levels had improved OS when treated with immunotherapy (HR 0.117, p = 0.036) and chemotherapy (HR 0.475, p = 0.017). Analysis of an scRNAseq dataset of 152,423 cells from 40 GCs revealed that T-cell and NK-cell proportions were higher (24% vs 18% and 19% vs 15%, p < 0.0001), while macrophage proportions were lower (7% vs 11%, p < 0.0001) in CD8PD-1high compared to CD8PD-1low tumors. CONCLUSION: This is one of the largest GC cohorts of mIHC combined with analysis of multiple datasets providing orthogonal validation of the clinical relevance of PD-1+CD8+ T-cells being associated with improved OS. CD8PD-1high tumors have distinct features of an immunologically active, T-cell inflamed TME.

Real-world outcomes from use of CDK4/6 inhibitors in the management of advanced/metastatic breast cancer in Asia.

Background: Oestrogen receptor positive, human epidermal growth factor receptor-2 (HER2) negative breast cancer (BC) is the most frequently diagnosed BC subtype. Combinations of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) with anti-oestrogen therapy have led to improved survival compared with anti-oestrogen therapy alone for advanced/metastatic BC. The evaluation of CDK4/6i in the real-world facilitates treatment planning, insights into the incidence of drug toxicities, dose modifications including dose delays (DDs) and dose reductions (DRs) and improves prognostic accuracy in subgroups, for example geriatric patients, who are under-represented in clinical trials. Methods: This multi-centre study analysed retrospective and prospective data from 456 patients treated with CDK4/6i between January 2015 and December 2020. We examined patient characteristics, variation in prescribing practices, efficacy and toxicity outcomes. Results: In all, 456 patients were included in this study. The median age was 59 (range: 24-92). In total, 85 (19%) were ⩾70 years old. In all, 122 (27%) and 119 (26%) of patients were treated in the first-line and second-line settings, respectively. In total, 25 (5%), 31 (7%) and 145 (32%) of patients had brain, peritoneum and liver metastasis, respectively, at the time of CDK4/6i initiation. On univariate analysis, heavily pre-treated patients and those with distant metastases, involving the liver, brain or peritoneum, had significantly shorter progression-free survival (PFS) and 24-month overall survival (OS). Elderly patients (⩾70) had a shorter PFS; OS results were not mature. Majority of patients (n = 362, 80%) initiated treatment with the United States FDA-approved starting dose of CDK4/6i. In all, 330 (72%) had at least one DD and 217 (48%) patients required at least one DR, but these dose modifications were not associated with poorer survival outcomes. Patients age ⩾70 were more likely to require dose modifications leading to a lower treatment dose. The most common reason for DD/DR was neutropenia (60%) and the incidence of febrile neutropenia was only 2%. Conclusions: Our study indicates CDK4/6i is effective and safe. Age ⩾ 70, distant metastases to liver, peritoneal or brain were negative prognostic factors. Age ⩾ 70 was associated with significantly increased requirement for dose modification; however, this did not impact survival outcomes. These findings provide reassurance that survival outcomes are not adversely affected in elderly patients when DD/DR is indicated.

Real-world experience of consolidation durvalumab after concurrent chemoradiotherapy in stage III non-small cell lung cancer.

BACKGROUND: Durvalumab consolidation is associated with improved survival following concurrent chemoradiotherapy (CCRT) in patients with stage III non-small cell lung cancer (NSCLC). Given the heterogeneity of stage III NSCLC patients, in this study we evaluated the efficacy and safety of durvalumab in the real-world setting. METHOD: Unresectable stage III NSCLC patients were retrospectively studied: one cohort received CCRT, another had CCRT-durvalumab. Primary endpoints were progression-free survival (PFS) and overall survival (OS), secondary endpoints were relapse rate and safety. In CCRT-durvalumab cohort, association between blood markers with survival and pneumonitis risk were analyzed. RESULTS: A total of 84 patients were enrolled: 45 received CCRT, and 39 received CCRT-durvalumab. Median PFS was 17.5 months for CCRT-durvalumab and 8.9 months for CCRT-alone (HR 0.47, p = 0.038). Median OS was not-reached for CCRT-durvalumab and 22.3 months for CCRT-alone (HR 0.35, p = 0.024). Both EGFR-positive and wild-type (WT) patients had numerically improved PFS with durvalumab consolidation compared to CCRT-alone, 17.5 versus 10.9 months and 11.8 versus 6.63 months, respectively (interaction p-value = 0.608). Grade 2+ pneumonitis was detected in 25% of patients in the durvalumab cohort. Most pneumonitis occurred at 3.5 weeks after durvalumab initiation. Baseline neutrophil-to-lymphocyte ratio (NLR) ≥ 3 and ≥5 were associated with shorter PFS with durvalumab. Week 6 platelet-lymphocyte-ratio ≥ 180 was associated with a lower risk of pneumonitis. CONCLUSION: In this real-world study, durvalumab consolidation post CCRT was associated with a statistically significant improvement in PFS and OS. Effect of durvalumab on PFS was not modified by EGFR status. Active surveillance for pneumonitis is crucial. Baseline NLR may help to predict the benefit of treatment with durvalumab.

Organizational Readiness for Implementing Change for Mentorship in Nurse Anesthesia Programs.

Student registered nurse anesthetists (SRNAs) undergo enormous stress related to the lifestyle changes that are necessary to commit to full-time training in nurse anesthesia programs (NAPs). Mentorship and mentoring initiatives have proved to provide positive support to enhance SRNA wellness. This interventional study was conducted to assess the status of mentorship and mentorship initiatives in NAPs and to understand and analyze the specific constructs of organizational change from the perspective of nurse anesthesia program directors toward mentorship after viewing an educational online video regarding the topics of stress of an SRNA, mentorship and formalized mentorship programs. NAP state of mentorship information from NAPDs (n = 36) was conducted to obtain the current descriptive statistics of mentorship in NAPs. An adapted Organizational Readiness for Implementing Change survey was conducted to assess for six constructs of change by applicable study participants (n = 26). Statistically significant increases in the median scores of change commitment, change valence, task knowledge, and resource availability were noted in study participants (P < .05), reflecting that education was able to increase organizational readiness for these specific constructs.

Outcomes of a Phase II Study of Intraperitoneal Paclitaxel plus Systemic Capecitabine and Oxaliplatin (XELOX) for Gastric Cancer with Peritoneal Metastases.

BACKGROUND: Adding intraperitoneal paclitaxel (IP-PTX) to paclitaxel/5-fluoropyrimidine has shown promising results in patients with gastric cancer peritoneal metastases (GCPM) but has not been studied with standard-of-care platinum/fluoropyrimidine combinations. Our goal to was evaluate IP-PTX with capecitabine/oxaliplatin (XELOX) in GCPM. METHODS: Forty-four patients with GCPM received IP PTX (40 mg/m2, Days 1, 8), oral capecitabine (1000 mg/m2 twice daily, Days 1-14) and intravenous oxaliplatin (100 mg/m2, Day 1) in 21-day cycles. Patients with synchronous GCPM underwent conversion surgery if they had good response after chemotherapy, conversion to negative cytology, no extraperitoneal metastasis, and no peritoneal disease during surgery. The primary endpoint was overall survival and secondary endpoints were progression-free survival and safety. Outcomes from the trial were compared against a matched cohort of 39 GCPM patients who received systemic chemotherapy (SC) comprising platinum/fluoropyrimidine. RESULTS: The median OS for the IP and SC groups was 14.6 and 10.6 months (hazard ratio [HR] 0.44; 95% confidence interval [CI], 0.26-0.74; p = 0.002). The median PFS for the IP and SC group was 9.5 and 4.4 months respectively (HR 0.39; 95% CI 0.25-0.66; p < 0.001). Patients in the SC group were younger (IP vs. SC, 61 vs. 56 years, p = 0.021) and had better performance status (ECOG 0, IP vs. SC, 47.7% vs. 76.9%, p = 0.007) compared with the IP cohort. In IP group, conversion surgery was performed in 36.1% (13/36) of patients, with a median OS of 24.2 (95% CI 13.1-35.3) months and 1-year OS of 84.6%. CONCLUSIONS: IP PTX with XELOX is a promising treatment option for GCPM patients. In patients with good response, conversion surgery was feasible with favourable outcomes.

Clinical characteristics and genetic testing outcome of suspected hereditary peripheral nerve sheath tumours in a tertiary cancer institution in Singapore.

BACKGROUND: Peripheral Nerve Sheath Tumors (PNST) are a diverse group of mostly benign tumours uncommon in the general population. About 5-10% of PNSTs are hereditary, predominantly arising from germline variants in NF1, NF2, SMARCB1, or LZTR1 gene. METHODS: We reviewed the clinical characteristics and genetic testing results of patients referred to the NCIS Adult Cancer Genetics Clinic for suspected hereditary PNST. RESULTS: 3,001 patients suspected to have various hereditary cancer syndromes were evaluated between year 2000 to March 2021. 13 (0.4%) were clinically diagnosed to have hereditary PNSTs. The majority were male (54%), with a median age at presentation to the genetics clinic of 29 years (range 19-48). 11/13 (85%) patients had multiple PNSTs, 12/13 (92%) had young onset PNSTs, 5/13 (38.5%) had personal and family history of PNST. 11/13 patients (85%) had clinical features of neurofibromatosis type 1 (NF1) including one patient who also fulfilled clinical criteria of neurofibromatosis type 2 (NF2); 2/13 (14%) had multiple schwannomas. Four patients underwent multi-gene panel testing, including one patient with clinical NF1, one patient who met both clinical NF1 and NF2 criteria, and two patients with multiple schwannomas. The patient with clinical features of NF1 was heterozygous for a pathogenic c. 2033dup variant in the NF1 gene. The patient with both NF1/NF2 features was heterozygous for a novel c.732 T > A nonsense variant in the NF2 gene. The two patients with multiple schwannomas were heterozygous for a pathogenic/likely pathogenic variant in the LZTR1 gene and are the first LZTR1-positive schwannomatosis patients reported in Asia. CONCLUSION: Hereditary PNSTs are rare referrals to an adult cancer genetics clinic. NF1 is the most common PNST seen. LZTR1 variants may be the underlying cause in Asian patients with multiple schwannomatosis.

Serial Tumor Molecular Profiling of Newly Diagnosed HER2-Negative Breast Cancers During Chemotherapy in Combination with Angiogenesis Inhibitors.

BACKGROUND: Breast cancers are heterogeneous with variable clinical courses and treatment responses. OBJECTIVE: We sought to evaluate dynamic changes in the molecular landscape of HER2-negative tumors treated with chemotherapy and anti-angiogenic agents. PATIENTS AND METHODS: Newly diagnosed HER2-negative breast cancer patients received low-dose sunitinib or bevacizumab prior to four 2-weekly cycles of dose-dense doxorubicin and cyclophosphamide. Tumor biopsies were obtained at baseline, after 2 weeks and after 8 weeks of chemotherapy. Next-generation sequencing was performed to assess for single nucleotide variants (SNVs) and copy number alterations (CNAs) of 440 cancer-related genes (ACTOnco®). Observed genomic changes were correlated with the Miller-Payne histological response to treatment. RESULTS: Thirty-four patients received sunitinib and 18 received bevacizumab. In total, 77% were hormone receptor positive (HER2-/HR+) and 23% were triple negative breast cancers (TNBC). New therapy-induced mutations were infrequent, occurring only in 13%, and appeared early after a single cycle of treatment. Seventy-two percent developed changes in the variant allele frequency (VAF) of pathogenic SNVs; the majority (51%) of these changes occurred early at 2 weeks and were sustained for 8 weeks. Changes in VAF of SNVs were most commonly seen in the PI3K/mTOR/AKT pathway; 13% developed changes in pathogenic mutations, which potentially confer sensitivity to PIK3CA inhibitors. Tumors with poor Miller-Payne response to treatment were less likely to experience changes in VAF of SNVs compared with those with good response (50% [7/14] vs 15% [4/24] had no changes observed at any timepoint, p = 0.029). CONCLUSIONS: Serial molecular profiling identifies early therapy-induced genomic alterations, which may guide future selection of targeted therapies in breast cancer patients who progress after standard chemotherapy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT02790580 (first posted June 6, 2016).

Phase Ib/II Dose Expansion Study of Lenvatinib Combined with Letrozole in Postmenopausal Women with Hormone Receptor-Positive Breast Cancer.

PURPOSE: RET is an estrogen response gene with preclinical studies demonstrating cross-talk between the RET and estrogen receptor (ER) pathways. We investigate the role of lenvatinib, a multikinase inhibitor with potent activity against RET, in patients with metastatic breast cancer. PATIENTS AND METHODS: Patients with advanced ER+/HER2- breast cancer were treated with lenvatinib plus letrozole in a phase Ib/II trial. Primary objectives included safety and recommended phase II dose (RP2D) determination in phase Ib, and objective response rates (ORR) in phase II dose expansion. RESULTS: Sixteen patients were recruited in dose finding, where deescalating doses of lenvatinib from 20 to 14 mg were investigated. Lenvatinib 14 mg plus letrozole 2.5 mg daily was determined as RP2D. Thirty-one patients with 5 median lines of prior therapy in the metastatic setting (range, 0-11) were recruited in dose expansion. In this cohort, ORR was 23.3% [95% confidence interval (CI) 9.9%-42.3%], with median duration of response (DoR) of 6.9 months [interquartile range (IQR) 5.9 to 13.1]. Clinical benefit rate ≥6 months (CBR) was 50.0% (95% CI, 31.3%-68.7%). Similar efficacy was observed in the subgroup of 25 patients who progressed on prior CDK4/6 inhibitor therapy [ORR 20.0% (95% CI, 6.8%-40.7%), median DoR 6.9 months (IQR 5.9-13.1), and CBR 52.0% (95% CI, 31.3%-72.2%)]. Pharmacodynamic studies showed target modulation, with paired tumor biopsies indicating downregulation of RET/pERK and improved vascular normalization index. CONCLUSIONS: Lenvatinib plus letrozole had manageable toxicity, with target engagement and preliminary antitumor activity observed, supporting further assessment in randomized studies.

An Innovative Model of Positive Education with Traditional Chinese Moral Values: An Evaluation of Project Bridge.

Project Bridge, as a new, contextualized positive education program, is designed to enhance university students' character strengths and moral development, resulting in the promotion of their psychological wellbeing. Taking into account the differences between Western and Chinese cultures, the project integrated both Western and Asian concepts and values in the delivery of university education that would likely bring about optimal outcomes. In the evaluation, mixed methods were applied to demonstrate the outcomes of this newly developed positive education program. Pre- and post-test, as well as reflective writing, were adopted to measure the outcomes. Both quantitative and qualitative results demonstrated satisfying outcomes. Implications and future developments are discussed in the conclusion.

Immunohistochemistry study of tumor vascular normalization and anti-angiogenic effects of sunitinib versus bevacizumab prior to dose-dense doxorubicin/cyclophosphamide chemotherapy in HER2-negative breast cancer.

PURPOSE: Tumor angiogenesis controlled predominantly by vascular endothelial growth factor and its receptor (VEGF-VEGFR) interaction plays a key role in the growth and propagation of cancer cells. However, the newly formed network of blood vessels is disorganized and leaky. Pre-treatment with anti-angiogenic agents can "normalize" the tumor vasculature allowing effective intra-tumoral delivery of standard chemotherapy. Immunohistochemistry (IHC) analysis was applied to investigate and compare the vascular normalization and anti-angiogenic effects of two commonly used anti-angiogenic agents, Sunitinib and Bevacizumab, administered prior to chemotherapy in HER2-negative breast cancer patients. METHODS: This prospective clinical trial enrolled 38 patients into a sunitinib cohort and 24 into a bevacizumab cohort. All received 4 cycles of doxorubicin/cyclophosphamide chemotherapy and pre-treatment with either sunitinib or bevacizumab. Tumor biopsies were obtained at baseline, after cycle 1 (C1) and cycle 4 (C4) of chemotherapy. IHC was performed to assess the tumor vascular normalization index (VNI), lymphatic vessel density (LVD), Ki67 proliferation index and expression of tumor VEGFR2. RESULTS: In comparison to Bevacizumab, Sunitinib led to a significant increase in VNI post-C1 and C4 (p < 0.001 and 0.001) along with decrease in LVD post-C1 (p = 0.017). Both drugs when combined with chemotherapy resulted in significant decline in tumor proliferation after C1 and C4 (baseline vs post-C4 Ki67 index p = 0.006 for Sunitinib vs p = 0.021 for Bevacizumab). Bevacizumab resulted in a significant decrease in VEGFR2 expression post-C1 (p = 0.004). CONCLUSION: Sunitinib, in comparison to Bevacizumab showed a greater effect on tumor vessel modulation and lymphangiogenesis suggesting that its administration prior to chemotherapy might result in improved drug delivery. TRIAL REGISTRY: ClinicalTrials.gov: NCT02790580 (first posted June 6, 2016).

An Inquiry into the Relationship between Drug Users' Psychological Situations and Their Drug-Taking Behaviour.

In view of the research gap whereby few studies have investigated the inner psychological situations underlying continuous drug use, this study used the Soulmate Scale to investigate the relationship between soulmate experience and drug-taking behaviour. Overall, 276 participants took part in this study. Results showed that soulmate experience was negatively related to drug-taking behaviour, which means that being psychologically attached to drugs and receiving comfort from them encourages dependency and a higher level of difficulty in quitting drugs. In addition, soulmate experience significantly mediated the effect of meaning of life and social isolation on drugs, suggesting that when such psychological bonding and sustenance can be developed in interpersonal relationships instead of drugs, drug users are likely to develop the meaning of life and a lower sense of social isolation, and are more likely to quit drugs. The corresponding implications were discussed.