Data and metadata supporting the published article: Immunostimulatory and anti-tumor metronomic cyclophosphamide regimens assessed in primary orthotopic and metastatic murine breast cancer
Bibliographic record
Abstract
The primary goal of this study was to comparatively evaluate three different cyclophosphamide (CTX) protocols for anti-tumor efficacy in three highly translatable murine breast cancer models with particular emphasis on an every 6 day metronomic-like regimen using a dose of 140 mg/kg (CTX1401q6d). Data access: All the datasets supporting figures 1-6 in the published article, are publicly available in the figshare repository as part of this figshare data record (https://doi.org/10.6084/m9.figshare.12383498). Datasets supporting the supplementary figures in the published article, are available on reasonable request from the corresponding authors Dr. Kabir Khan, email address: kkhan@sri.utoronto.ca, and Dr Robert Kerbel, email address robert.kerbel@sri.utoronto.ca. Study approval: Animal experiments were carried out with the approval of the institutional Animal Care Committee in accordance to Canadian Council on Animal Care (CCAC) guidelines. Study aims and methodology: The purpose of this study was to address three related questions. First, what is the comparative effectiveness of three different CTX regimens, one being a maximum tolerated dose (MTD) protocol, a second being low dose daily/continuous oral metronomic CTX, and the third being the CTX140 1q6d regimen. Second, what is the evidence for immunological mechanisms mediating anti-tumor efficacy of the CTX140 1q6d regimen? Third, would concomitant use of the immune system boosting CTX140 1q6d regimen improve outcomes of PD-L1 antibody therapy? For in vitro experiments, the following cell lines were used: EMT6/P (EMT6-parental), EMT6-CDDP (EMT6-cisplatin resistant) and SP1-AC2M2.For the animal experiments, female BALB/c, CBA/J, and SCID CB-17 mice were purchased from Jackson Laboratories. Female SCID Beige (CB17.Cg- rkdcscidLystbg-J/Crl) mice were purchased from Charles River Laboratories.The following techniques are described in more detail in the published article: in vivo therapies, postsurgical metastasis studies, 4H-CTX in vitro studies, flow cytometry, CyTOF acquisition and analysis, immunohistochemistry, and statistical analysis. Dataset descriptions:The datasets generated during this study are Figure_1.xlsx, Figure_2.xlsx, Figure_3.xlsx, Figure_4.xlsx, Figure_5.xlsx and Figure_6.xlsx are in .xlsx file format, and support figures 1, 2, 3, 4, 5 and 6 respectively.This data record also includes the following datasets in .fcs file format: YS20170831_Control.fcs, YS20170831_CTX1401q6d.fcs, YS20170831_LDM_CTX.fcs and YS20170831_MTD_CTX.fcs. The .fcs file include the CyTOF data, and support figure 3C.The rar zip file Khan_et_al_2020_NPJBC_supplementarydata.rar supports supplementary figures 1-8 in the published article. These files will be made available on request as described in the Data access section above. Figure_1.xlsx: a Raw tumor volumes of mice bearing EMT6/P treated with either saline control, MTD CTX, LDM CTX continuous daily or CTX140 1q6d. b Endpoint data from Figure 1a for survival analyses. C Raw tumor volumes of SCID Beige mice bearing EMT6/P treated with either saline control, MTD CTX, LDM CTX continuous daily or CTX140 1q6d. d Endpoint data from Figure 1c. e Tumor volume comparison at 32 days post implantation in BALB/c wild type, SCID and SCID Beige mice all treated with CTX140 1q6d. Percentage change of mouse weights from 1a also included.Figure_2.xlsx: a Raw tumor volume data of CBA/J mice bearing SP1-AC2M2 tumors treated with either saline control, MTD CTX, LDM CTX continuous or CTX140 1q6d. b Survival data from Figure 2a when mice reached tumor endpoint as a surrogate for survival. c Raw tumor volume data of mice displaying complete responses that were re-challenged with SP1-AC2M2 in the opposite mammary fat pad to the original implantation. d Raw tumor volumes of SP1-AC2M2 primary tumors were treated with CTX140 1q6d (blue arrows), a break was initiated after 5 doses. Percentage change of mouse weights from 2a also included.Figure_3.xlsx: a Raw tumor volumes of mice bearing EMT6-CDDP treated with either saline control, MTD CTX, LDM CTX continuous daily or CTX140 1q6d. b Endpoint survival data from Figure 3a. Percentage change of mouse weights from 3a also included.Figure_4.xlsx: b Endpoint survival data from EMT6-CDDP adjuvant treatment experiment. c Percentage values of lung metastasis visualised by immunohistochemical staining using Ki67 as a marker for proliferation. Percentage change of mouse weights from 4b also included.Figure_5.xlsx: b Adjusted mean values of fluorescence of EMT6-CDDP, c EMT6/P, or d SP1-AC2M2 cells treated with 20 µM 4-HCTX or 1 µM of PTX, values represent mean fluorescence intensity of PD-L1 analysed by flow cytometry with subtraction of mean fluorescence intensity of isotype IgG.Figure_6.xlsx: a Raw tumor volumes of EMT6-CDDP treated concomitantly with either IgG isotype control or PD-L1 (6E11) blockade in combination with each regimen of CTX or saline control. b Endpoint survival data from Figure 6a. c Raw tumor volumes from induction therapy with CTX140 1q6d then followed up with either IgG isotype or anti PD-L1 in EMT6-CDDP model. Percentage change of mouse weights from 6a also included. Software needed to access data: The flow cytometry files in .fcs file format can be accessed and analysed using a software such as FloJo. The files are fully annotated for which channels refer to which cell markers were used.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.008 | 0.089 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.009 | 0.012 |
| Science and technology studies | 0.003 | 0.002 |
| Scholarly communication | 0.008 | 0.005 |
| Open science | 0.004 | 0.005 |
| Research integrity | 0.005 | 0.003 |
| Insufficient payload (model declined to judge) | 0.658 | 0.284 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".