Cancer Outcomes Research Articles

Soluble immune checkpoint molecules in cancer risk, outcomes prediction, and therapeutic applications.

Immunotherapy has emerged as a pivotal modality in cancer treatment, with immune checkpoint inhibitors effectively combating malignancies by impeding crucial pathways within the immune system and stimulating patients' immune responses. Soluble forms of immune checkpoints exhibit a remarkable diversity and can be readily tracked in circulation, holding immense potential as biomarkers for cancer treatment. An increasing number of studies focused on soluble immune checkpoints in cancer have emerged thanks to technological advancements. In this systematic review, we comprehensively summarized the recent studies on soluble immune checkpoints in human cancer risk prediction, outcome prediction, therapeutic applications, and potential molecular mechanisms, which demonstrated the promising future of soluble immune checkpoints in clinical applications. The clinical relevance of soluble immune checkpoints has been recognized in multiple cancers, yet the therapeutic applications and mechanisms remain obscure. Interpreting the impacts and mechanisms of soluble immune checkpoints could shed a light on the novel strategies of cancer screening, treatments, and outcome prediction.

Perioperative toripalimab plus neoadjuvant chemotherapy might improve outcomes in resectable esophageal cancer: an interim analysis of a phase III randomized clinical trial.

In the era of immunotherapy, neoadjuvant immunochemotherapy (NAIC) for the treatment of locally advanced esophageal squamous cell carcinoma (ESCC) is used clinically but lacks of high-level clinical evidence. This study aimed to compare the safety and long-term efficacy of NAIC followed by minimally invasive esophagectomy (MIE) with those of neoadjuvant chemotherapy (NAC) followed by MIE. A prospective, single-center, open-label, randomized phase III clinical trial was conducted at Henan Cancer Hospital, Zhengzhou, China. Patients were randomly assigned to receive either neoadjuvant toripalimab (240 mg) plus paclitaxel (175 mg/m2) + cisplatin (75 mg/m2) (toripalimab group) or paclitaxel + cisplatin alone (chemotherapy group) every 3 weeks for 2 cycles. After surgery, the toripalimab group received toripalimab (240 mg every 3 weeks for up to 6 months). The primary endpoint was event-free survival (EFS). The pathological complete response (pCR) and overall survival (OS) were key secondary endpoints. Adverse events (AEs) and quality of life were also assessed. Between May 15, 2020 and August 13, 2021, 252 ESCC patients ranging from T1N1-3M0 to T2-3N0-3M0 were enrolled for interim analysis, with 127 in the toripalimab group and 125 in the chemotherapy group. The 1-year EFS rate was 77.9% in the toripalimab group compared to 64.3% in the chemotherapy group (hazard ratio [HR] = 0.62; 95% confidence interval [CI] = 0.39 to 1.00; P = 0.05). The 1-year OS rates were 94.1% and 83.0% in the toripalimab and chemotherapy groups, respectively (HR = 0.48; 95% CI = 0.24 to 0.97; P = 0.037). The patients in the toripalimab group had a higher pCR rate (18.6% vs. 4.6%; P = 0.001). The rates of postoperative Clavien-Dindo grade IIIb or higher morbidity were 9.8% in the toripalimab group and 6.8% in the chemotherapy group, with no significant difference observed (P = 0.460). The rates of grade 3 or 4 treatment-related AEs did not differ between the two groups (12.5% versus 12.4%). The interim results of this ongoing trial showed that in resectable ESCC, the addition of perioperative toripalimab to NAC is safe, may improve OS and might change the standard treatment in the future.

Inhalable explosive nanosensor for real-time visual monitoring of therapeutic effects of lung cancer

Lung cancer, as one of the major diseases that endanger human health, has a very high fatality rate. Consequently, effective evaluation of clinical treatment outcomes for lung cancer is crucial for the formulation of subsequent treatment plans for patients. In this work, we utilized amorphous calcium carbonate nanoparticles (CaCO3 NPs) as sources of calcium ions (Ca2+) to develop CPs (CaCO3@PDA) core–shell nanoprobes. Concurrently, we functionalized the surface of gold nanoparticles with Cy5.5-peptide, AS1411, and (4-aminosulfonylphenyl) boronic acid (4-APBA) to produce APAAs (Au NPs@pep-AS1411-(4-APBA)), which were further assembled with CPs using PEG to construct an innovative explosive nanosensor, CPAs (CaCO3@PDA-APAAs). The CPs component of the nanosensor could cause the release of a substantial amount of Ca2+ in response to the tumor microenvironment (TME), which in turn induced cellular Ca2+ overload and subsequent apoptosis. This event triggers caspase-3 activation, causing the cleavage of a specific peptide sequence (DEVD), resulting in the fluorescence signal being reinstated. Additionally, the 4-APBA moiety on the probe interacted with H2O2 resulting in alterations in surface-enhanced Raman spectroscopy (SERS) signals, which aided in the detection of reactive oxygen species (ROS) during the physiological processes. By utilizing atomization, the nanoprobes were strategically deposited in the affected lung regions to enhance the fluorescence imaging capabilities and effectively mirror the therapeutic outcomes. Overall, the CPAs explosive nanosensor has a potential in advancing the non-invasive visual monitoring of lung cancer prognosis and can be a valuable tool in ongoing efforts to improve the management of this challenging disease.

Analysis of neoadjuvant therapy effect on 30-day postoperative outcomes in gallbladder cancer

BackgroundThe role of neoadjuvant therapy (NAT) in gallbladder cancer (GBC) is not well established. We sought to evaluate the effect of NAT on postoperative outcomes following surgical resection of GBC. We hypothesized that patients receiving NAT would have similar rates of 30-day mortality, readmission, and postoperative complications (e.g. bile leakage and liver failure) compared to those who did not receive NAT. MethodsThe 2014–2017 American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) Procedure-Targeted Hepatectomy database was queried for patients that underwent surgery for GBC. Propensity scores were calculated to match patients in a 1:2 ratio based on age, comorbidities, functional status, and tumor staging. ResultsA total of 37 patients undergoing NAT were matched to 74 patients without NAT. There was no difference in any matched characteristics. Compared to the NAT group, the no NAT cohort had similar rates of postoperative bile leakage (NAT 13.5 % vs. no NAT 10.8 %, p = 0.31), postoperative liver failure (5.4 %, vs. 8.1 %, p = 0.60), 30-day readmission (10.8 % vs. 10.8 %, p = 1.00), and 30-day mortality (10.8 % vs. 2.7 %, p = 0.075). All 30-day complications were similar except for a higher rate of postoperative blood transfusion (NAT 32.4 % vs. no NAT 10.8 %, p = 0.005). ConclusionIn patients undergoing surgical resection for GBC, those with and without NAT had similar rates of readmission and 30-day mortality, however NAT was associated with an increased risk for transfusion. Despite use of a large national database, this study may be underpowered to adequately assess the effect of NAT on perioperative GBC outcomes and thus warrants further investigation.

Helicobacter pylori infection facilitates cell migration and potentially impact clinical outcomes in gastric cancer

Gastric cancer is a significant health concern worldwide. Helicobacter pylori (HP) infection is associated with gastric cancer risk, but differences between HP-infected and HP-free gastric cancer have not been studied sufficiently. The objective of this study was to investigate the effects of HP infection on the viability and migration of gastric cancer cells and identify potential underlying genetic mechanisms as well as their clinical relevance. Cell counting kit-8, lactate dehydrogenase, wound healing, and transwell assay were applied in the infection model of multiple clones of HP and multiple gastric cancer cell lines. Genes related to HP infection were identified using bioinformatics analysis and subsequently validated using real-time quantitative PCR. The association of these genes with immunity and drug sensitivity of gastric cancer was analyzed. Results showed that HP has no significant impact on viability but increases the migration of gastric cancer cells. We identified 1405 HP-upregulated genes, with their enriched terms relating to cell migration, drug, and immunity. Among these genes, the 82 genes associated with survival showed a significant impact on gastric cancer in consensus clustering and LASSO prognostic model. The top 10 hub HP-associated genes were further identified, and 7 of them were validated in HP-infected cells using real-time quantitative PCR, including ERBB4, DNER, BRINP2, KCTD16, MAPK4, THPO, and VSTM2L. The overexpression experiment showed that KCTD16 medicated the effect of HP on gastric cancer migration. Our findings suggest that HP infection may enhance the migratory potential of gastric cancer cells and these genes might be associated with immunity and drug sensitivity of gastric cancer. In human subjects with gastric cancer, HP presence in tumors may affect migration, immunity, and drug sensitivity.

Textbook outcome in low rectal cancer after neoadjuvant chemoradiotherapy: post hoc analysis of the LASRE randomized clinical trial

BackgroundTextbook outcome has been incorporated into quality assessment measures in various oncology settings; however, it has not been applied to patients with low rectal cancer after neoadjuvant chemoradiotherapy (nCRT). This study aimed to examine the prevalence and predictors of achieving a textbook outcome in patients undergoing surgical resection of low rectal cancer after nCRT. Patients and methodsThis study was a post hoc subgroup analysis of the prospective multicentric LASRE trial, which specifically enrolled patients with rectal cancer located within 5 cm from the dentate line at diagnosis, tumors with diameters less than 6 cm, and patients who underwent radical laparoscopic or open resection. A total of 597 patients who had clinically staged cT3-4aN0-2M0 tumors with diameters less than 6 cm and who underwent neoadjuvant chemoradiotherapy followed by radical resection were included. ResultsTextbook outcome was achieved in 60.0% of patients. Multivariate logistic regression analysis revealed that body mass index > 25 kg/m2 (OR = 0.594, P = 0.01), tumor distance from the anal verge > 40 mm (OR = 5.518, P < 0.001), operative time > 202 minutes (OR = 0.675, P = 0.04), and laparoscopic approach (OR = 1.497, P = 0.04) were independently predictive factors for the achievement of a textbook outcome in low rectal cancer patients undergoing nCRT and radical resection. A predictive nomogram for achieving a textbook outcome was constructed, yielding a C-index of 0.724. ConclusionsLaparoscopic resection exhibited promising potential in improving the probability of achieving a textbook outcome.

52417 Efficacy of the Minority Outreach for High School Students (MOHSS) Program in Addressing Racial and Ethnic Disparities in Skin Cancer Awareness and Outcomes

52417 Efficacy of the Minority Outreach for High School Students (MOHSS) Program in Addressing Racial and Ethnic Disparities in Skin Cancer Awareness and Outcomes

Advancements in Biotechnology and Stem Cell Therapies for Breast Cancer Patients.

This comprehensive review article examines the integration of biotechnology and stem cell therapy in breast cancer diagnosis and treatment. It discusses the use of biotechnological tools such as liquid biopsies, genomic profiling, and imaging technologies for accurate diagnosis and monitoring of treatment response. Stem cell-based approaches, their role in modeling breast cancer progression, and their potential for breast reconstruction post-mastectomy are explored. The review highlights the importance of personalized treatment strategies that combine biotechnological tools and stem cell therapies. Ethical considerations, challenges in clinical translation, and regulatory frameworks are also addressed. The article concludes by emphasizing the potential of integrating biotechnology and stem cell therapy to improve breast cancer outcomes, highlighting the need for continued research and collaboration in this field.

A traffic light approach for treatment and supportive care stratification in lung cancer.

Comprehensive supportive care interventions for patients with lung cancer are being investigated in a range of ways, including: early palliative care, prehabilitation and rehabilitation. We review recent literature on supportive care and propose a traffic light system to individualise comprehensive supportive care. Green for those very likely to receive anti-cancer treatment, red for those very unlikely to receive anti-cancer treatment and orange where the chance of accessing treatment is uncertain. Comprehensive supportive care can be individualised based on the group a particular patient is in. Lung cancer outcomes are improving with the availability of increasingly efficacious treatments; however, treatment rates for advanced disease remain low. In this review, we discuss how person-centred outcomes could be improved, how outcomes can be prognosticated and how the 'host' can be staged as well as the cancer. Recent data suggests that early comprehensive supportive care improves quality of life, reduces time spent in hospital and may affect survival. Comprehensive supportive care is likely to improve quality of life in patients with advanced lung cancer. Further work is needed to see if it can improve treatment rates and survival.

Writers, readers, and erasers RNA modifications and drug resistance in cancer.

Drug resistance in cancer cells significantly diminishes treatment efficacy, leading to recurrence and metastasis. A critical factor contributing to this resistance is the epigenetic alteration of gene expression via RNA modifications, such as N6-methyladenosine (m6A), N1-methyladenosine (m1A), 5-methylcytosine (m5C), 7-methylguanosine (m7G), pseudouridine (Ψ), and adenosine-to-inosine (A-to-I) editing. These modifications are pivotal in regulating RNA splicing, translation, transport, degradation, and stability. Governed by "writers," "readers," and "erasers," RNA modifications impact numerous biological processes and cancer progression, including cell proliferation, stemness, autophagy, invasion, and apoptosis. Aberrant RNA modifications can lead to drug resistance and adverse outcomes in various cancers. Thus, targeting RNA modification regulators offers a promising strategy for overcoming drug resistance and enhancing treatment efficacy. This review consolidates recent research on the role of prevalent RNA modifications in cancer drug resistance, with a focus on m6A, m1A, m5C, m7G, Ψ, and A-to-I editing. Additionally, it examines the regulatory mechanisms of RNA modifications linked to drug resistance in cancer and underscores the existing limitations in this field.

Report on post-transplantation cancer in southeast Asia from the Thai kidney transplantation cohort.

Post-transplantation cancer is a significant cause of mortality among kidney transplant recipients (KTR). The incidence of post-transplantation cancer varies based on geographic region and ethnicity. However, data on KTR from South East Asia, where characteristics differ from other parts of Asia, is lacking. We conducted a retrospective cohort study at a transplant center in Thailand to investigate the incidence of post-transplantation cancer and mortality rates. Factors associated with post-transplantation cancer and patient outcomes were analyzed using competing-risks regression. The study included 1156 KTR with a post-transplant follow-up duration of 5.1 (2.7-9.4) years. The age- and sex-adjusted incidence rate of post-transplant cancer was highest for urothelial cancer (6.9 per 1000 person-years), which also resulted in the highest standardized incidence ratio (SIR) of 42.5 when compared to the general population. Kidney cancer had the second-highest SIR of 24.4. Increasing age was the factor associated with an increased risk of post-transplant cancer (SHR 1.03; 95% CI 1.01-1.05). Human leukocyte antigen (HLA) DR mismatch was associated with a decreased risk of post-transplant cancer (SHR 0.72; 95% CI 0.52-0.98). Post-transplantation cancer was significantly associated with patient mortality (HR 3.16; 95% CI 2.21-4.52). Cancer significantly contributes to KTR mortality, and the risk profile for cancer development in Thai KTRs differs from that of Western and most Asian counterparts. Further research is essential to explore appropriate screening protocols for countries with high rates of urothelial and kidney cancer, including Thailand.

Racial Comparisons in Treatment of Rectal Adenocarcinoma and Survival in the Military Health System.

Racial disparities in treatment and outcomes of rectal cancer have been attributed to patients' differential access to care. We aimed to study treatment and outcomes of rectal cancer in the equal access Military Health System (MHS) to better understand potential racial disparities. We accessed the MilCanEpi database to study a cohort of patients aged 18 and older who were diagnosed with rectal adenocarcinoma between 1998 and 2014. Receipt of guideline recommended treatment per tumor stage, cancer recurrence, and all-cause death were compared between Non-Hispanic White and Black patients using multivariable regression models with associations expressed as odds (AORs) or hazard ratios (AHRs) and their 95% confidence intervals (CIs). The study included 171 Black and 845 White patients with rectal adenocarcinoma. Overall, there were no differences in receipt of guideline concordant treatment (AOR = 0.76, 95% CI = 0.45, 1.29), recurrence (AHR = 1.34, 95% CI = 0.85, 2.12), or survival (AHR = 1.08, 95% CI = 0.77, 1.54) for Black patients compared to White patients. However, Black patients aged <50 years at diagnosis (AOR = 0.34, 95% CI 0.13, 0.90) or with stage III or IV tumors (AOR = 0.28, 95% CI = 0.12, 0.64) were less likely to receive guideline recommended treatment than White patients in stratified analysis. In the equal access MHS, while there were no overall racial disparities in rectal cancer treatment or clinical outcomes between Black and White patients, disparities among those with early-onset or late-stage rectal cancers were noted. This suggests factors other than access to care may play a role in the observed disparities and warrants further research.

Real-world treatment costs of first-line treatment for metastatic colorectal cancer: a survey of the JCOG colorectal cancer study group.

Although treatment outcomes for metastatic colorectal cancer (mCRC) have dramatically improved over the past few decades, drug costs have also significantly increased. This study aimed to investigate which first-line treatment regimens for mCRC are actually used (frequency) in Japanese practice and at what cost. We collected data on patients with mCRC who received first-line treatment at 37 institutions of the Japan Clinical Oncology Group Colorectal Cancer Study Group from July 2021 to June 2022, and calculated the cost of regimens. The cost per month of each regimen was estimated based on standard usage, assuming a patient with a weight of 70kg and a body surface area of 1.8m2. We categorized the regimens into very high-cost (≥1 000 000 Japanese yen [JPY]/month), high-cost (≥500 000 JPY/month), and others (<500 000 JPY/month). The study included 1880 participants, 24% of whom were≥75years. Molecular targeted containing regimens were received by 78% of the patients. The most frequently used regimen was the doublet regimen (fluoropyrimidine with either oxaliplatin or irinotecan) plus bevacizumab (43%), followed by doublet plus cetuximab or panitumumab (21%). The cost of molecular targeted drugs-containing regimens (ranging from 85 406 to 843 602 JPY/month) is much higher than that of only cytotoxic drug regimens (ranging from 17 672 to 51 004 JPY/month). About 16% received high-cost treatments that included panitumumab-containing regimens and pembrolizumab (17% of patients aged ≤74years and 11% of patients aged ≥75years). About 16% of mCRC patients received first-line treatment with regimens costing >500 000JPY/month, and molecular targeted drugs being the main drivers of cost.

Gerotherapeutics: Aging Mechanism-based Pharmaceutical and Behavioral Interventions to Reduce Cancer Racial and Ethnic Disparities.

The central premise of this article is that a portion of the established relationships between social determinants of health and racial/ethnic disparities in cancer morbidity and mortality are mediated through differences in rates of biological aging processes. We further posit that using knowledge about aging could enable discovery and testing of new mechanism-based pharmaceutical and behavioral interventions ("gerotherapeutics") to differentially improve the health of minoritized cancer survivors and reduce cancer disparities. These hypotheses are based on evidence that lifelong differences in adverse social determinants of health contribute to disparities in rates of biological aging ("social determinants of aging"), with minoritized groups having accelerated aging (ie, a steeper slope or trajectory of biological aging over time relative to chronological age) more often than non-minoritized groups. Acceleration of biological aging can increase the risk, age of onset, aggressivity and/or stage of many adult cancers. There are also documented negative feedback loops whereby the cellular damage caused by cancer and its therapies act as drivers of additional biological aging. Together, these dynamic intersectional forces can contribute to differences in cancer outcomes between minoritized vs non-minoritized survivor populations. We highlight key targetable biological aging mechanisms with potential applications to reducing cancer disparities and discuss methodological considerations for pre-clinical and clinical testing of the impact of gerotherapeutics on cancer outcomes in minoritized populations. Ultimately, the promise of reducing cancer disparities will require broad societal policy changes that address the structural causes of accelerated biological aging and ensure equitable access to all new cancer control paradigms.

Association between renal dysfunction and outcomes of lung cancer: A systematic review and meta‑analysis

Association between renal dysfunction and outcomes of lung cancer: A systematic review and meta‑analysis

Postoperative Radiotherapy Using VMAT for RNI Including IMN in Breast Cancer: Report of Short-term Follow-up.

The application of volumetric-modulated arc therapy (VMAT) in postoperative radiotherapy for breast cancer has recently garnered considerable interest, especially when regional lymph node irradiation (RNI), is extended to include the internal mammary node (IMN) region, along with whole-breast or chest wall irradiation. This study aimed to assess both acute and late toxicities, as well as breast cancer outcomes, during the observation period. This retrospective study aimed to assess the safety and feasibility of VMAT in postoperative radiotherapy, including the IMN region, for patients with breast cancer at our hospital. We included 33 eligible patients who received postoperative VMAT radiotherapy, including the IMN region, between November 2018 and July 2021. The primary indications for implementing VMAT were the presence of IMN metastases before primary systemic therapy or more than four axillary lymph node metastases. The median prescribed dose for the chest wall or conserved breast and regional lymph nodes was 50 Gy in 25 fractions. In 16 cases, a simultaneous boost (median, 10 Gy) was administered to residual lymph node metastases. VMAT facilitated a reduction in the mid- or high-dose range to organs at risk, exemplified by V20Gy and V40Gy of the ipsilateral lung, which were 24.10% and 6.84%, respectively, while ensuring adequate target dose irradiation, V45Gy=95.23%. No serious adverse events, including symptomatic radiation pneumonitis, occurred during the 15-month median observation period. Our findings demonstrate the safety and effectiveness of postoperative radiotherapy for breast cancer, including the IMN region, when using VMAT.

Outcomes of rectal cancer treatment in rural Australia and New Zealand: analysis of the bowel cancer outcomes registry.

The demographics and geography of Australia and New Zealand (ANZ), with few metropolitan centres and vast, sparsely populated rural areas, represent a challenge to providing equal care to all patients. This study aimed to compare rectal cancer care at rural and urban hospitals in ANZ. From the Bowel Cancer Outcomes Registry (BCOR, formerly known as the Bi-National Colorectal Cancer Audit; BCCA), rectal cancer patients treated between 2007 and 2020 were compared based on hospital location (urban versus rural). Propensity-score matching was performed to correct for differences in baseline characteristics between groups. A total of 9385 rectal cancer patients were identified from the BCOR: 1329 (14.2%) were treated at rural hospitals and 8056 (85.8%) at urban hospitals. Propensity-score matching resulted in 889 patients in each group, matched for age, ASA score, hospital type (public/private), tumour height from the anal verge, and pre-treatment cT- and cAJCC-stage. Rural patients had fewer pre-treatment MRIs (67.9% versus 74.7%; P = 0.002), and underwent less neoadjuvant therapy (44.7% versus 50.9%; P = 0.01). Rural patients underwent fewer ULARs (39.4% versus 45.6%; P = 0.03), and fewer anastomoses were formed (67.9% versus 74.4%; P = 0.05). CRM rates and postoperative AJCC stages (P = 0.19) were similar between groups (P = 0.87). Fewer rural patients received adjuvant chemotherapy (37.8% versus 43.3%; P = 0.02). There are significant differences in pre-treatment MRI rates, (neo)adjuvant treatment rates and surgical procedures performed between rectal cancer patients treated at rural and urban hospitals in ANZ, while CRM rates and postoperative AJCC stages are similar.

Lung cancer mortality trends and disparities: A cross-sectional analysis 1999–2020

BackgroundLung cancer remains a leading cause of morbidity and mortality in the United States. Given the importance of epidemiological insight on lung cancer outcomes as the foundation for targeted interventions, we aimed to examine lung cancer death trends in the United States in the recent 22-year period, exploring demographic disparities and yearly mortality shifts. MethodsMortality information was obtained from the CDC Wide-ranging Online Data for Epidemiologic Research database from the years 1999–2020. Demographic information included age, sex, race or ethnicity, and area of residence. We performed log-linear regression models to assess temporal mortality shifts and calculated average annual percentage change (AAPC) and compared age-adjusted mortality rates (AAMR) across demographic subpopulations. ResultsA total of 3,380,830 lung cancer deaths were identified. The AAMR decreased from 55.4 in 1999-31.8 in 2020 (p<0.001). Males (AAMR 57.6) and non-Hispanic (NH) (AAMR 47.5) populations were disproportionately impacted compared to females (AAMR 36.0) and Hispanic (AAMR 19.1) populations, respectively. NH Black populations had the highest AAMR (48.5) despite an overall reduction in lung cancer deaths (AAPC −3.3 %) over the study period. Although non-metropolitan regions were affected by higher mortality rates, the annual decrease in mortality among metropolitan regions (AAPC −2.8 %, p<0.001) was greater compared to non-metropolitan regions (AAPC −1.7 %, p<0.001). Individuals living in the Western US (AAPC −3.4 %, p<0.001) experienced the greatest decline in lung cancer mortality compared to other US census regions. ConclusionsOur findings revealed lung cancer mortality inequalities in the US. By contextualizing these mortality shifts, we provide a larger framework of data-driven initiatives for societal and health policy changes for improving access to care, minimizing healthcare inequalities, and improving outcomes.

ZBTB7A forms a heterodimer with ZBTB2 and inhibits ZBTB2 homodimerization required for full activation of HIF-1

Hypoxia-inducible factor 1 (HIF-1), recognized as a master transcription factor for adaptation to hypoxia, is associated with malignant characteristics and therapy resistance in cancers. It has become clear that cofactors such as ZBTB2 are critical for the full activation of HIF-1; however, the mechanisms downregulating the ZBTB2-HIF-1 axis remain poorly understood. In this study, we identified ZBTB7A as a negative regulator of ZBTB2 by analyzing protein sequences and structures. We found that ZBTB7A forms a heterodimer with ZBTB2, inhibits ZBTB2 homodimerization necessary for the full expression of ZBTB2-HIF-1 downstream genes, and ultimately delays the proliferation of cancer cells under hypoxic conditions. The Cancer Genome Atlas (TCGA) analyses revealed that overall survival is better in patients with high ZBTB7A expression in their tumor tissues. These findings highlight the potential of targeting the ZBTB7A-ZBTB2 interaction as a novel therapeutic strategy to inhibit HIF-1 activity and improve treatment outcomes in hypoxia-related cancers.

Changes in Skeletal Muscle Volume During Preoperative Chemotherapy Affect the Outcome of Pancreatic Cancer.

This study aimed to investigate the effects of changes in clinicopathological factors during preoperative chemotherapy for pancreatic cancer, including skeletal muscle volume, on recurrence and prognosis after pancreatectomy. Data from 41 patients who underwent resection for pancreatic cancer after preoperative chemotherapy from 2012 to 2021 were retrospectively reviewed. Skeletal muscle volume was substituted for the psoas muscle area (PMA) at the level of the third lumbar vertebra. We investigated the relationship of clinicopathological factors during preoperative chemotherapy with disease-free survival (DFS) and overall survival (OS). The association between clinicopathological factors and a decrease in PMA was investigated. In the multivariate analyses for DFS and OS, the factors associated with recurrence were as follows: decrease in PMA (P = 0.003) and the absence of adjuvant therapy (P = 0.03), and the factors associated with poor prognosis were as follows: decrease in PMA (P = 0.04) and the absence of adjuvant therapy (P = 0.008), and the resectability of borderline resectable and unresectable-locally advanced tumors (P = 0.033). All patients with partial response according to the Response Evaluation Criteria in Solid Tumors (version 1.1) had no decrease in PMA (P = 0.01). The proportion of patients with Evans classification ≥ II was significantly higher in the group without a decrease in PMA (P = 0.02). The proportion of patients with an average relative dose intensity of adjuvant therapy ≥0.6 was significantly higher in the group without a decrease in PMA (P = 0.02). Changes in preoperative skeletal muscle volume during preoperative chemotherapy for pancreatic cancer is a potential predictor of recurrence and prognosis after pancreatectomy.